lignans and sesamin

Neurodegenerative Diseases (NDs) are characterized by progressive neuronal deterioration as a result of several pathogenesis mechanisms. Phytochemicals, including sesamin with multitarget activities, have been studied widely.. In this review, we aim to survey the neuroprotective effects of sesamin on NDs and its mechanisms of action.. Searching GoogleScholar, PubMed, and Science Direct databases, we reviewed original English language articles on sesamin effects against NDs, specifically Alzheimer's Disease (AD) and Parkinson's Disease (PD), either in vivo or in vitro settings, with no time limitation.. Sesamin has been reported to interfere with NDs progression through its antioxidative, antiinflammatory, and antiapoptotic actions in most of the retrieved studies. Sesamin also can prevent amyloid-β aggregation in AD models and elevate dopamine levels in PD-induced models.. The results of this study revealed the beneficial effects of sesamin in the prevention and management of NDs, including AD and PD; however, no clinical data supporting these effects in humans is available, which highlights the need for designing clinical trials to evaluate the efficacy, proper dosage, pharmacokinetics aspects, and possible side effects of sesamin in humans.

Topics: Alzheimer Disease; Dioxoles; Humans; Lignans; Parkinson Disease

This systematic review aimed to appraise and recapitulate all research investigations to elucidate the effects of Sesamum indicum preparations on managing the cardiometabolic syndrome of Diabetes mellitus (DM) and metabolic syndrome (MetS).. A systematic review was carried out in a Cochrane fashion and in compliance with the PRISMA checklist using the published academic works in PubMed/MEDLINE, WOS, SCOPUS, and EMBASE databases that were searched up to June 2021. Abstracts that met PICO criteria for qualitative studies were duplicate reviewed for data extraction to assess the quality and details of the study.. Sesamum indicum preparations and its bioactive lignans, such as sesamin, sesamol, and pinoresinol, were found to possess anti-hyperglycemic, anti-hyperlipidemia, anti-inflammatory, antioxidative, anti-hypertensive, cardioprotective, and hepatoprotective effects both in patients with T2DM as well as in experimental animal models with T1DM and MetS. The incorporation of sesame oil as a natural adjuvant can be effective in improving vascular reactivity and aortic permeability, reproductive parameters, and diabetic nephropathy, as well as modification of anthropometry indices. Therefore, sesame oil and bioactive lignans as combination therapy with drugs can exhibit synergistic effects and provide a favorable preference in clinical settings.. Sesame oil and lignans present in it act in a dose-dependent manner. The best dosage to improve risk biomarkers of patients with T2DM and MetS is 30-35 ml daily of sesame oil or inclusion of sesame oil in daily dietary patterns up to 30% of total energy for 8-12 weeks and/or 200 mg daily of sesamin supplementation for eight weeks.

Topics: Animals; Diabetes Mellitus, Type 2; Humans; Lignans; Metabolic Syndrome; Seeds; Sesame Oil; Sesamum

Doxorubicin (DOX) is a potent antitumor agent with a broad spectrum of activity; however, irreversible cardiotoxicity resulting from DOX treatment is a major issue that limits its therapeutic use. Sirtuins (SIRTs) play an essential role in several physiological and pathological processes including oxidative stress, apoptosis, and inflammation. It has been reported that SIRT1 and SIRT3 can act as a protective molecular against DOX-induced myocardial injury through targeting numerous signaling pathways. Several natural compounds (NCs), such as resveratrol, sesamin, and berberine, with antioxidative, anti-inflammation, and antiapoptotic effects were evaluated for their potential to suppress the cardiotoxicity induced by DOX via targeting SIRT1 and SIRT3. Numerous NCs exerted their therapeutic effects on DOX-mediated cardiac damage via targeting different signaling pathways, including SIRT1/LKB1/AMPK, SIRT1/PGC-1α, SIRT1/NLRP3, and SIRT3/FoxO. SIRT3 also ameliorates cardiotoxicity by enhancing mitochondrial fusion.

Topics: Animals; Berberine; Cardiotoxicity; Dioxoles; Doxorubicin; Heart Diseases; Humans; Lignans; Myocardium; Sirtuin 1; Sirtuin 3

Sesamin, the main lignin constituent of sesame, plays a pivotal role in regulating physical state. Some studies have evidenced that the supplementation of sesamin may decrease cardiovascular disease risk. The goal of this systematic review was to summarize evidence of the effects of sesamin supplementation on obesity, blood pressure, and lipid profile in humans by performing a meta-analysis of randomized controlled trials.. Five databases (PubMed, Cochrane Library, EMBASE, Web of Science, and Scopus) were searched electronically from inception to July 2021 to identify randomized controlled trials that assessed the impact of sesamin on obesity, blood pressure, and lipid profile. Weighted mean difference (WMD) and standard deviation (SD) were used to present the major outcomes.. Seven trials (n = 212 participants) were included in the overall analysis. Results showed that sesamin supplementation caused a great reduction in TC (WMD: -10.893 mg/dl, 95% CI: -19.745 to -2.041, p = 0.016), LDL-c (WMD: -8.429 mg/dl, 95% CI: -16.086 to -0.771, p = 0.031), and SBP (WMD: -3.662 mmHg, 95% CI: -6.220 to -1.105, p = 0.005), whereas it had no effect on HDL-c, TG, DBP, or weight. Subgroup analysis showed that duration, parallel design, and unhealthy status can affect TC, LDL-c, and SBP evidently. We did not discover a strong link between indicators' changes and duration of supplementation. Sesamin can be used as an obtainable dietary supplement to improve blood pressure and blood lipids, and further as a health product to prevent cardiovascular diseases.

Topics: Blood Pressure; Cholesterol, LDL; Dietary Supplements; Dioxoles; Humans; Lignans; Lipids; Obesity; Randomized Controlled Trials as Topic

Topics: Anti-Inflammatory Agents; Dioxoles; Humans; Immunity; Inflammation; Lignans; Sesamum

A large body of evidence indicates that lignans as polyphenolic compounds are beneficial against life-threatening diseases such as cancer. Plant lignans have the potential to induce cancer cell death and interfere with carcinogenesis, tumor growth, and metastasis. Epidemiological studies have revealed that the intake of lignans is inversely associated with the risk of several cancers. Moreover, numerous experimental studies demonstrate that natural lignans significantly suppress cancer cell proliferation with minimal toxicity against non-transformed cells. Dietary lignans arctigenin and sesamin have been found to have potent antiproliferative activities against various types of human cancer. The purpose of this review is to provide the reader with a deeper understanding of the cellular and molecular mechanisms underlying anticancer effects of arctigenin and sesamin. Our review comprehensively describes the effects of arctigenin and sesamin on the signaling pathways and related molecules involved in cancer cell proliferation and invasion. The findings of present review show that the dietary lignans arctigenin and sesamin seem to be promising carcinopreventive and anticancer agents. These natural lignans can be used as dietary supplements and pharmaceuticals for prevention and treatment of cancer.

Topics: Antineoplastic Agents; Cell Line, Tumor; Dioxoles; Furans; Humans; Lignans; Neoplasms

Major lignans of sesame sesamin and sesamolin are benzodioxol--substituted furofurans. Sesamol, sesaminol, its epimers, and episesamin are transformation products found in processed products. Synthetic routes to all lignans are known but only sesamol is synthesized industrially. Biosynthesis of furofuran lignans begins with the dimerization of coniferyl alcohol, followed by the formation of dioxoles, oxidation, and glycosylation. Most genes of the lignan pathway in sesame have been identified but the inheritance of lignan content is poorly understood. Health-promoting properties make lignans attractive components of functional food. Lignans enhance the efficiency of insecticides and possess antifeedant activity, but their biological function in plants remains hypothetical. In this work, extensive literature including historical texts is reviewed, controversial issues are critically examined, and errors perpetuated in literature are corrected. The following aspects are covered: chemical properties and transformations of lignans; analysis, purification, and total synthesis; occurrence in

Topics: Benzodioxoles; Dioxoles; Furans; Lignans; Oxidation-Reduction; Phenols; Seeds; Sesamum

Pseudomonas aeruginosa is an opportunistic pathogen emerging as a public health threat owing to their multidrug resistance profiles. The quorum sensing systems of P. aeruginosa play a pivotal role in the regulation of virulence and act as the target for the development of alternative therapeutics. The study discussed about anti-quorum sensing and antibiofilm properties of lignans (sesamin and sesamolin) found in Sesamum indicum (L.) against P. aeruginosa. The effect of lignans, sesamin and sesamolin on LasR/RhlR mediated virulence factor production, biofilm formation and bacterial motility were studied. To elucidate the mechanism of action of lignans on QS pathways, QS gene expression and in depth in silico analysis were performed. Both the lignans exerted anti-quorum sensing activity at 75 μg/ml without affecting the growth of bacteria. SA and SO exhibited decreased production of virulence factors such as pyocyanin, proteases, elastase and chitinase. The important biofilm constituents of P. aeruginosa including alginate, exopolysaccharides and rhamnolipids were strongly affected by the lignans. Likewise, plausible mechanism of action of lignans were determined through the down regulation of QS regulated gene expression, molecular docking and molecular simulation studies. The in vitro analysis was supported by C. elegans infection model. SA and SO rescued pre-infected worms within 8 days of post infection and reduced the colonization of bacteria inside the intestine due to the anti-infective properties of lignans. The lignans exhibited profound action on Las pathway rather than Rhl which was elucidated through in vitro and in silico assays. In silico pharmacokinetic analysis portrayed the opportunities to employ ligands as potential therapeutics for human use. The deep insights into the anti-QS, anti-biofilm and mechanism of action of lignans can contribute to the development of novel anti-infectives against pseuodmonal infections.

Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Biofilms; Caenorhabditis elegans; Dioxoles; Humans; Lignans; Molecular Docking Simulation; Pseudomonas aeruginosa; Pseudomonas Infections; Quorum Sensing; Virulence Factors

Sesamin is the major lignan constituent derived from Sesamum indicum seeds and sesame oil. Various studies have reported that sesamin possesses potent lipid-lowering properties. The lipid-lowering effects of sesamin have been mainly attributed to its ability in affecting key events in fatty acid and cholesterol metabolism and in lowering atherogenesis-triggering LDL, VLDL and TG levels, as well as in increasing atheroprotective HDL levels. In this review, we provide a comprehensive summary of the reported anti-hyperlipidemic effects of sesamin, presented both in vitro and in vivo. The molecular anti-hyperlipidemic properties of sesamin that underlie its well-documented anti-atherogenic effects are thoroughly discussed and analyzed. Studies focusing on the ability of sesamin to inhibit fatty acid synthesis, induce fatty acid oxidation, inhibit cholesterol synthesis and absorption and maintain macrophage cholesterol homeostasis are outlined. The effects of sesamin on circulating serum and liver lipid levels are also highlighted. Moreover, the anti-hyperlipidemic effects of sesamin are compared to those of other important sesame lignans like sesamolin and episesamin. Findings reveal that sesamin mainly exerts its anti-hyperlipidemic effects by targeting Δ5 desaturase, HMGCR, ABCA1 and ABCG1 through PPARα, PPARγ, LXRα, and SREBP signaling pathways. Overall, the amount of evidence supporting the anti-hyperlipidemic potential of sesamin in vitro and in vivo is compelling. A thorough understanding of the mechanisms underlying the anti-hyperlipidemic properties of sesamin is imperative for the possible employment of sesamin as an anti-hyperlipidemic and anti-atherogenic agent with minimal side effects.

Topics: Animals; Anticholesteremic Agents; Cholesterol; Dioxoles; Fatty Acids; Humans; Lignans; Lipid Metabolism; Macrophages

Sesamin is the major active ingredient is Sesamum indicum seeds. Several studies revealed that sesamin possesses potent anti-cancer properties. The anti-cancer effects of sesamin have been mainly attributed to its anti-proliferative, pro-apoptotic, anti-inflammatory, anti-metastatic, anti- and pro-angiogenic, and pro-autophagocytic activities. In this review, we provide a comprehensive summary of the reported anti-cancer effects of sesamin, both in vitro and in vivo. Experimental findings related to the potential of sesamin to attenuate oxidative stress, inflammation, proliferation, metastasis, and angiogenesis in various cancer cells and tumors are analyzed. Studies focusing on the ability of sesamin to induce apoptosis and autophagy in cancer cells are also underscored. Moreover, the molecular mechanisms underlying the anti-cancer effects of sesamin are highlighted, and the major signaling pathways targeted by sesamin are identified. Although the exact signaling events triggered by sesamin in cancer cells are not fully revealed, our analysis indicates that NF-κB, STAT3, JNK, ERK1/2, p38 MAPK, PI3K/AKT, caspase-3, and p53 signaling pathways are critically involved in mediating the anti-cancer effects of sesamin. In sum, the experimental evidence suggesting that sesamin could exert potent anti-cancer activities in vitro and in vivo is compelling. Hence, sesamin can potentially be employed as an effective adjuvant therapeutic agent in ameliorating tumor development and progression, and therefore, it could be used in the prevention and/or treatment of various types of cancer.

Topics: Animals; Antineoplastic Agents; Dioxoles; Humans; Lignans; Neoplasms; Seeds; Sesamum

Tocotrienol (T3), unsaturated vitamin E, is gaining a lot of attention owing to its potent anticancer effect, since its efficacy is much greater than that of tocopherol (Toc). Various factors are known to be involved in such antitumor action, including cell cycle arrest, apoptosis induction, antiangiogenesis, anti-metastasis, nuclear factor-κB suppression, and telomerase inhibition. Owing to a difference in the affinity of T3 and Toc for the α-tocopherol transfer protein, the bioavailability of orally ingested T3 is lower than that of Toc. Furthermore, cellular uptake of T3 is interrupted by coadministration of α-Toc in vitro and in vivo. Based on this, several studies are in progress to screen for molecules that can synergize with T3 in order to augment its potency. Combinations of T3 with chemotherapeutic drugs (e.g., statins, celecoxib, and gefitinib) or dietary components (e.g., polyphenols, sesamin, and ferulic acid) exhibit synergistic actions on cancer cell growth and signaling pathways. In this review, we summarize the current status of synergistic effects of T3 and an array of agents on cancer cells, and discuss their molecular mechanisms of action. These combination strategies would encourage further investigation and application in cancer prevention and therapy.

Topics: Antineoplastic Agents; Catechin; Coumaric Acids; Dietary Supplements; Dioxoles; Drug Synergism; Drug Therapy, Combination; Humans; Lignans; Neoplasms; Resveratrol; Stilbenes; Tocotrienols

Acanthopanax senticosus (previously classified as Eleutherococcus senticosus), commonly known as Ciwujia or Siberian Ginseng, is a traditional Chinese medicine (TCM), widely used for its high medicinal value, such as antifatigue, anti-inflammation, antistress, anti-ulcer and cardiovascular functions, in China, Korea, Japan and Russia. In the past decades, researchers worldwide have conducted systematic investigations on this herb, from chemistry to pharmacology, and a large number of chemical components have been characterized for their significant pharmacological effects. However, reports about the anticancer effects of this plant had been rare until recently, when considerable pharmacological experiments both in vitro and in vivo were conducted to study the anticancer effects of this herb. A. senticosus has been found to have inhibitory effects on malignant tumors, such as those in the lung and liver, suggesting that A. senticosus has potential to be developed as an effective anticancer drug. This paper reviews recent findings on the pharmacological properties of A. senticosus, with a focus on its anticancer effects.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Coumarins; Dioxoles; Dose-Response Relationship, Drug; Eleutherococcus; Glucosides; Humans; Immunologic Factors; Lignans; Medicine, Chinese Traditional; Mice; Phenylpropionates; Phytotherapy; Rats

Although sesame seed oil contains high levels of unsaturated fatty acids and even a small amount of free fatty acids in its unrefined flavored form, it shows markedly greater stability than other dietary vegetable oils. The good stability of sesame seed oil against autoxidation has been ascribed not only to its inherent lignans and tocopherols but also to browning reaction products generated when sesame seeds are roasted. Also, there is a strong synergistic effect among these components. The lignans in sesame seed oil can be categorized into two types, i.e. inherent lignans (sesamin, sesamolin) and lignans mainly formed during the oil production process (sesamol, sesamolinol, etc.). The most abundant tocopherol in sesame seed oil is γ-tocopherol. This article reviews the antioxidant activities of lignans and tocopherols as well as the browning reaction and its products in sesame seed and/or its oil. It is concluded that the composition and structure of browning reaction products and their impacts on sesame ingredients need to be further studied to better explain the remaining mysteries of sesame oil.

Topics: Antioxidants; Benzodioxoles; Diet; Dioxoles; gamma-Tocopherol; Humans; Lignans; Phenols; Seeds; Sesame Oil; Sesamum

Topics: Acetic Acid; Animals; Antihypertensive Agents; Catechin; Dioxoles; Diterpenes, Kaurane; Docosahexaenoic Acids; Eicosapentaenoic Acid; Functional Food; gamma-Aminobutyric Acid; Garlic; Glucosides; Humans; Hypertension; Lignans; Onions

Sesamin is a major lignan found in sesame and is known to have various biological effects. Some of these biological effects occur following its metabolic conversion to corresponding catechols and, therefore, the study of sesamin metabolism is quite important. There is currently a need to identify the enzymes responsible for metabolism of sesamin so that scientists will be more able to predict sesamin-drug interactions.. The authors reviewed all the published literature with a focus on papers that dealt with metabolism of sesamin by drug-metabolising enzymes in rat and/or human liver, such as cytochrome P450 and UDP-glucuronosyltransferase. The article also reviews papers that dealt with the inhibition of enzymes by sesamin including drug-metabolising enzymes and other physiologically important enzymes. Additionally, the authors discuss the species-based differences in the metabolism of sesamin between rats and humans.. A remarkable species-based difference was found in sesamin metabolism between humans and other animals; thus, it is very important that precautions are taken when predicting the physiological effects in humans from animal data. A mechanism-based inhibition of human CYP2C9 by sesamin was recently discovered, suggesting that it is important to evaluate the interaction between sesamin and drugs that are mainly metabolised by CYP2C9. Furthermore, further analysis of sesamin and episesamin and their molecular mechanisms are needed to make better use of sesamin supplements.

Topics: Animals; Cytochrome P-450 Enzyme System; Dioxoles; Glucuronosyltransferase; Humans; Lignans; Liver; Oxidation-Reduction; Sesamum; Tissue Distribution

The effects of phytochemicals (lignans and neolignans) are reviewed in a variety of insect species with special focus on the recent advances on feeding, excretion and Trypanosoma cruzi interactions with Rhodnius prolixus. Burchellin, podophyllotoxin, pinoresinol, sesamin, licarin A, and nordihydroguaiaretic acid (NDGA) added to the diet of Rhodnius prolixus larvae induce antifeedant effects only in doses up to 100 microg/ml of blood meal. Additionally, pinoresinol and NDGA significantly inhibit ecdysis (ED(50)<20 microg/ml). Simultaneous application of ecdysone (1 microg/ml) counteracts ecdysial stasis as induced by NDGA in 5th-instar larvae. Experiments in vivo demonstrate that burchellin and podophyllotoxin (100 microg/ml) diminish excretion post-feeding. Simultaneous treatment with 5-hydroxytryptamine (1 mM, 5-HT), a diuretic hormone, partially reverses this effect of burchellin. Experiments in vitro, using isolated Malpighian tubules of R. prolixus, indicate that burchellin (i) decreases diuretic hormone levels in the hemolymph but not the amount of diuretic hormone stored in the thoracic ganglionic masses (including axons); (ii) reduces the volume of urine secreted by isolated Malpighian tubules; and (iii) 5-HT therapy cannot overcome the effect of burchellin on the Malpighian tubules. In R. prolixus fed on blood containing T. cruzi epimastigotes, the number of parasites in the digestive tract decreases drastically in the presence of burchellin and NDGA (10 microg/ml). When these phytochemicals are applied 20 days after T. cruzi infection, burchellin significantly reduces the gut infection, whereas NDGA does not. However, if the insects are pretreated with both compounds 20 days before subsequent infection with epimastigotes, the parasite infection is almost completely abolished. The same holds true when 5th-instar of R. prolixus are inoculated with 0.5 microg/microl/larva of both neolignans 1 day before infection. Taken together, these findings not only provide a better understanding of the lignoid function in insects, but also offer novel insights into basic physiological processes, which make lignoids interesting candidates for new types of insecticides.

Topics: Animals; Benzofurans; Dioxoles; Feeding Behavior; Furans; Host-Parasite Interactions; Insecta; Larva; Lignans; Malpighian Tubules; Masoprocol; Molting; Podophyllotoxin; Rhodnius; Trypanosoma cruzi

Inflammation is one of the main characteristics of rheumatoid arthritis. Based on the antiinflammatory properties of sesame, this study was conducted to evaluate the sesamin supplement effects on serum levels of some proteolytic enzymes, inflammatory biomarkers, and clinical indices in women with rheumatoid arthritis. In this randomized, triple-blind, placebo-controlled clinical trial, 44 patients were randomly divided in intervention and control groups. Patients received 200-mg/day sesamin supplement or placebo in the intervention and control group for 6 weeks. Serum levels of proteolytic enzymes (hyaluronidase, aggrecanase, and matrix metalloproteinases-3) and inflammatory biomarkers (hs-CRP, IL-1β, IL-6, TNF-α, and cyclooxygenase-2) were measured with enzyme-linked immunosorbent assay method at the beginning and end of the study. After intervention, serum levels of hyaluronidase and matrix metalloproteinases-3 decreased significantly in sesamin group. Also, serum levels of hs-CRP, TNF-α, and cyclooxygenase-2 in intervention group were significantly decreased in intervention group compared with placebo group. Sesamin supplementation also caused a significant reduction in the number of tender joints and severity of pain in these patients. According to the results, it seems that the sesamin by reducing inflammatory mediators can relieve clinical symptoms and pathological changes that caused by inflammatory impairment in patients with rheumatoid arthritis.

Topics: Antioxidants; Arthritis, Rheumatoid; Biomarkers; Dietary Supplements; Dioxoles; Double-Blind Method; Female; Humans; Inflammation; Lignans; Middle Aged; Peptide Hydrolases

Severe fatigue can negatively affect quality of life, and oxidative stress may play a role in its mechanism. The aim of this study was to evaluate the effect of dietary supplementation of astaxanthin and sesamin (AS), strong food-derived antioxidants, on fatigue. Twenty-four healthy volunteers were supplemented with AS and placebo, each for four weeks. After each supplementation period, participants underwent tasks inducing mental and physical fatigue (visual display terminal task and ergometer task, respectively). Subjective fatigue was evaluated using a visual analogue scale during and after the mental and physical tasks, and daily subjective fatigue was evaluated by the Chalder fatigue questionnaire. Secondary outcomes included other subjective feelings, work efficiency, autonomic nerve activity, levels of an oxidative stress marker (plasma phosphatidylcholine hydroperoxide (PCOOH)) and safety. AS supplementation was associated with significantly improved recovery from mental fatigue compared with placebo. Increased PCOOH levels during mental and physical tasks were attenuated by AS supplementation. No differences between AS and placebo were detected in secondary outcomes, and no adverse effects of AS supplementation were observed. In conclusion, AS supplementation may be a candidate to promote recovery from mental fatigue which is experienced by many healthy people.

Topics: Adult; Antioxidants; Biomarkers; Cross-Over Studies; Dietary Supplements; Dioxoles; Double-Blind Method; Female; Health Status; Humans; Japan; Lignans; Lipid Peroxidation; Male; Mental Fatigue; Mental Health; Middle Aged; Neuropsychological Tests; Oxidative Stress; Phosphatidylcholines; Recovery of Function; Surveys and Questionnaires; Time Factors; Treatment Outcome; Xanthophylls

Dementia and its first or transitional stage, mild cognitive impairment (MCI), is a major concern for the aging Japanese society. Thus, the use of dietary supplements to improve or maintain cognitive function has become a topic of public interest.. In this study, we evaluated the effects of a composite supplement containing food-derived antioxidants, specifically astaxanthin and sesamin (AS), on cognitive function in people with MCI.. Twenty-one healthy participants with MCI were recruited in our double-blind placebo-controlled pilot study. They were assigned to either an AS group, who received ingestible capsules containing AS, or a placebo group, who received identical placebo capsules. To assess cognitive functions, we performed the Japanese version of the Central Nervous System Vital Signs (CNSVS) test and the Alzheimer's Disease Assessment Scale-Cog test at baseline, after 6 weeks, and after 12 weeks of dietary supplementation.. The CNSVS test revealed significant improvements in psychomotor speed and processing speed in the AS group compared with the placebo group, suggesting that the daily supplementation of AS improved cognitive functions related to the ability to comprehend, and perform complex tasks quickly and accurately.. Our results provide support for the use of AS as a dietary supplementation for improving cognitive functions.

Topics: Aged; Cognitive Dysfunction; Dietary Supplements; Dioxoles; Double-Blind Method; Female; Humans; Lignans; Male; Middle Aged; Neuropsychological Tests; Pilot Projects; Treatment Outcome; Xanthophylls

A single-blind, placebo-controlled, parallel-group and multiple oral dose study was conducted in 48 healthy subjects to investigate the pharmacokinetics and safety of multiple oral doses of sesame lignans (sesamin and episesamin). Subjects were randomly divided into two groups. Each subject was administered 50 mg of sesame lignans (sesamin/episesamin=1/1) or placebo once daily for 28 days. The pharmacokinetics of the sesame lignans were investigated using 10 of the 24 subjects in the sesame lignans group. No serious adverse events were observed in this study. Sesamin was absorbed with a peak plasma concentration at 5.0 h. The plasma concentration of the main metabolite, SC-1, reached a peak at 5.0 h and decreased rapidly with a terminal half-life of 2.4 h. Episesamin was also absorbed with a peak plasma concentration at 5.0 h and decreased with a terminal half-life of 7.1 h. The plasma concentration of the main metabolite, EC-1, reached a peak at 5.0 h and decreased rapidly with a terminal half-life of 3.4 h. The plasma concentrations of sesamin and episesamin reached a steady state by day 7. Sesame lignans were confirmed to be safe and tolerable in healthy subjects. The results of the pharmacokinetic study demonstrate that no accumulation was observed following multiple 50 mg doses of sesame lignans.

Topics: Adult; Dioxoles; Female; Humans; Lignans; Male; Middle Aged; Sesamum; Young Adult

This was a randomized, parallel, and placebo-controlled study. Forty subjects were divided into a test group and a placebo group. The study was focused on the potential effects of a mixture of Schisandra fruit extract and sesamin (hereinafter called 'SCH') in the subjects with borderline high levels (40-60 U/L) of alanine aminotransferase (ALT) or aspartate aminotransferase (AST). Twenty subjects taking SCH (four tablets per day) and 20 subjects taking a placebo (four tablets per day) were studied. The effects of SCH on ALT, AST, total bilirubin, direct bilirubin, free radical levels, total antioxidant status, glutathione peroxidase, glutathione reductase, and the lag time for low-density lipoprotein oxidation were determined. The total test period was 5 months. Intervention of SCH clearly reduced the levels of ALT and AST, but it made no change in the total bilirubin and direct bilirubin. Intake of SCH also greatly increased the antioxidant capacity and decreased the values of thiobarbituric acid reactive substances, total free radicals, and superoxide anion radicals in the plasma. The activities of glutathione peroxidase and reductase in the erythrocytes were significantly increased. In addition, the lag time for low-density lipoprotein oxidation, an inflammatory marker, was evidently increased. Fatty liver was found to have been significantly improved in this study. SCH proved to have the effects of antioxidation and improving liver function.

Topics: Adult; Aged; Alanine Transaminase; Antioxidants; Aspartate Aminotransferases; Bilirubin; Dioxoles; Female; Fruit; Glutathione Peroxidase; Glutathione Reductase; Humans; Lignans; Liver; Liver Function Tests; Male; Middle Aged; Oxidative Stress; Plant Extracts; Schisandra; Superoxides; Thiobarbituric Acid Reactive Substances; Young Adult

Sesamin, one of the lignans contained in sesame, has been considered to have medicinal effects. It has been reported that sesamin suppressed the development of hypertension in rats. In this study, using a double-blind, cross-over, placebo-controlled trial, we investigated the effect of 4-wk administration of sesamin on blood pressure (BP) in mildly hypertensive humans. Twenty-five middle-aged subjects with mild hypertension were divided into two groups, matched by age and body mass index. Twelve subjects were allocated to 4-wk intake of capsules with 60 mg sesamin per day and 13 subjects to 4-wk intake of a placebo (period 1). After a 4-wk washout period, the subjects received the alternative administration for 4 wk (period 2). BP decreased with statistical significance with the administration of sesamin (systolic: 137.6+/-2.2 to 134.1+/-1.7 mmHg, p=0.044, diastolic: 87.7+/-1.3 to 85.8+/-1.0 mmHg, p=0.045), but little changed with the placebo (systolic: 135.0+/-1.8 to 135.1+/-1.7 mmHg, diastolic: 85.9+/-1.2 to 86.6+/-1.2 mmHg). In conclusion, 4-wk administration of 60 mg sesamin significantly decreased BP by an average of 3.5 mmHg systolic BP and 1.9 mmHg diastolic BP. These results suggest that sesamin has an antihypertensive effect in humans. Epidemiological studies suggested that a 2-3 mmHg decrease in BP reduces the rate of cardiovascular diseases; therefore, it is considered that BP reduction achieved by sesamin may be meaningful to prevent cardiovascular diseases.

Topics: Antihypertensive Agents; Blood Pressure; Dioxoles; Double-Blind Method; Female; Humans; Hypertension; Lignans; Male; Middle Aged; Phytotherapy; Plant Extracts; Seeds; Sesamum

Sesamin, the major lignan found in sesame, has been shown to increase vitamin E levels by inhibiting its metabolism via the cytochrome P450 isozyme CYP4F2. CYP4F2 and CYP4A11 are the predominant human isoforms that synthesize 20-hydroxyeicosatetraenoic acid (20-HETE) from arachidonic acid. Considerable evidence suggests that 20-HETE may play a role in the pathogenesis of hypertension. We hypothesized that sesamin could be an inhibitor of 20-HETE synthesis. This study investigated the effects of sesamin on 20-HETE synthesis in vitro and the effect of sesame supplementation on plasma and urinary 20-HETE concentrations in humans. Human microsomes were used to investigate the potency and selectivity of sesamin inhibition of 20-HETE synthesis. Sesamin inhibited human renal and liver microsome 20-HETE synthesis with IC50 <20 micromol/L. It was selective toward CYP4F2 (IC50: 1.9 micromol/L) and had reduced activity toward CYP4A11 (IC50: >150 micromol/L), as well as cytochrome P epoxygenation of arachidonic acid (IC50: >50 micromol/L). In a randomized, controlled crossover trial, overweight men and women (n=33) consumed 25 g/d of sesame (approximately 50 mg/d of sesame lignan) or an isocaloric matched control for 5 weeks each. Relative to control, sesame supplementation resulted in a 28% decrease in plasma and a 32% decrease in urinary 20-HETE (P<0.001). Urinary sodium, potassium, and blood pressure were not affected. This study demonstrates for the first time that sesame supplementation in humans reduces the plasma and urinary levels of 20-HETE, likely via inhibition of CYP4F2 by sesame lignans. These results suggest that sesame lignans could be used for the investigation of potential roles of 20-HETE in humans.

Topics: Antihypertensive Agents; Dietary Supplements; Dioxoles; Female; Humans; Hydroxyeicosatetraenoic Acids; Hypertension; In Vitro Techniques; Lignans; Male; Microsomes, Liver; Middle Aged; Plant Extracts; Probability; Reference Values; Treatment Outcome

Topics: Anticholesteremic Agents; Cholesterol; Dioxoles; Humans; Lignans; Lipids; Male

This study explored the effects of sesamin on nonalcoholic steatohepatitis (NASH). High-fat and high-fructose diet-fed mice supplemented with or without sesamin. The results suggested that sesamin-treated mice lost body weight and fat tissue weight, had lower levels of serum metabolic parameters, and insulin resistance was mitigated. Histological examinations showed that sesamin treatment mitigated the progression of hepatic steatosis, and inflammation. In addition, sesamin enhanced hepatic antioxidant capacity, and decreased the activations of hepatic c-jun N-terminal kinase, inhibitor of kappa B kinase α, and insulin receptor substrate 1 as well as hepatic interleukin-6 and tumor necrosis factor-alpha levels. Further experiments indicated that sesamin treatment downregulated GRP78 and phospho-inositol-requiring enzyme 1 (IRE1) expression, and upregulated x-box binding protein 1 (XBP1) expression in hepatic tissue. The aforementioned results suggest that sesamin alleviates obesity-associated NASH, which might be linked to the effect of sesamin on the regulation of the hepatic endoplasmic reticulum stress-IRE1/XBP1 pathway. Thus, sesamin may be a good food functional ingredient in the treatment of obesity-associated NASH.

Topics: Animals; Diet; Diet, High-Fat; Dioxoles; Fructose; Lignans; Liver; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Obesity; Protein Serine-Threonine Kinases

Cellular senescence induces inflammation and is now considered one of the causes of organismal aging. Accumulating evidence indicates that age-related deterioration of mitochondrial function leads to an increase in reactive oxygen species (ROS) and DNA damage, which in turn causes cellular senescence. Thus, it is important to maintain mitochondrial function and suppress oxidative stress in order to inhibit the accumulation of senescent cells. Sesamin and its isomer episesamin are types of lignans found in sesame oil, and after being metabolized in the liver, their metabolites have been reported to exhibit antioxidant properties. However, their effects on cellular senescence remain unknown. In this study, the effects of sesamin, episesamin, and their metabolites SC1 and EC1-2 on replicative senescence were evaluated using human diploid lung fibroblasts, and TIG-3 cells. The results showed that sesamin and episesamin treatment had no effect on proliferative capacity compared to the untreated late passage group, whereas SC1 and EC1-2 treatment improved proliferative capacity and mitigated DNA damage of TIG-3 cells. Furthermore, other cellular senescence markers, such as senescence-associated secretory phenotype (SASP), mitochondria-derived ROS, and mitochondrial function (ROS/ATP ratio) were also reduced by SC1 and EC1-2 treatment. These results suggest that SC1 and EC1-2 can maintain proper mitochondrial function and suppress the induction of cellular senescence.

Topics: Cellular Senescence; Humans; Lignans; Liver; Reactive Oxygen Species

Sesamin, the major lignan in sesame seeds (Sesamum indicum L.), is known to have several pharmaceutical activities. However, its toxicological profile is still limited, especially regarding embryotoxicity. This study aimed to evaluate the developmental toxicity of sesamin in zebrafish embryos. After 72 h exposure, sesamin did not affect the survival and hatching rates, nor did it cause malformation in zebrafish embryos. Cardiotoxicity was also evaluated by monitoring embryo heartbeats and erythrocyte staining using o-dianisidine. The results showed that sesamin did not affect heart morphology, heart rate, or cardiac output in zebrafish embryos. The present study also evaluated sesamin's anti-angiogenesis, antioxidant and anti-inflammation activities. Sesamin significantly decreased the sub-intestinal vessel plexus as revealed by alkaline phosphatase staining indicating the compound exhibited anti-angiogenesis activity. For the antioxidant and anti-inflammatory assays, oxidative stress and inflammation in zebrafish embryos were induced by hydrogen peroxide and lipopolysaccharide, respectively. The reactive oxygen species (ROS) and nitric oxide (NO) production were detected using a fluorescent dye. Sesamin significantly decreased ROS and NO production in zebrafish embryos. In addition, the transcription examination by qRT-PCR of oxidative- and inflammation-related genes showed that sesamin affected the genes in a manner that correlated with results from the efficacy assays. In conclusion, the present study revealed that sesamin did not cause embryotoxicity and cardiotoxicity in zebrafish embryos. In addition, it exhibited evidence of anti-angiogenesis, antioxidant and anti-inflammatory activities.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cardiotoxicity; Embryo, Nonmammalian; Inflammation; Lignans; Oxidative Stress; Reactive Oxygen Species; Zebrafish

This study aimed to improve the steaming process of black sesame seeds. A comprehensive evaluation was conducted using the grey-correlation method based on the variation-coefficient weight to observe the treatments of normal-pressure (NPS) and high-pressure (HPS) steaming (with/without soaking in water) for nine cycles. Their effects on the contents of water, protein, fat, ash, melanin, sesamin, and sesamolin of black sesame seeds, as well as the sensory score of the black sesame pill, were determined. We found that with varied steaming methods and increased steaming cycles, the contents of the nutritional and functional components of black sesame seeds and the sensory score of the black sesame pill differed. The results of the variation-coefficient method showed that water, protein, fat, ash, melanin, sesamin, sesamolin, and sensory score had different effects on the quality of black sesame seeds with weighting factors of 34.4%, 5.3%, 12.5%, 11.3%, 13.9%, 11.3%, 7.8%, and 3.5%, respectively. The results of two-factor analysis of variance without repeated observations indicated that the grey-correlation degree of HPS was the largest among the different steaming treatments, and the following sequence was HPS after soaking in water (SNPS), NPS, and SNPS. There was no significant difference between NPS and SNPS (

Topics: Lignans; Melanins; Seeds; Sesamum; Steam

Topics: AMP-Activated Protein Kinases; Calcium-Calmodulin-Dependent Protein Kinase Kinase; Estrogen Receptor alpha; Hep G2 Cells; Humans; Lignans; Lipid Metabolism; Liver; Molecular Docking Simulation; Non-alcoholic Fatty Liver Disease; Palmitates; Signal Transduction; Sterol Regulatory Element Binding Protein 1

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease that lacks effective treatment modalities. Once patients are diagnosed with IPF, their median survival is approximately 3-5 years. PPARγ is an important target for the prevention and treatment of pulmonary fibrosis. Asarinin is a lignan compound that can be extracted from food plant Asarum heterotropoides. In this study, we investigated the therapeutic effects of asarinin in a pulmonary fibrosis model constructed using bleomycin in mice and explored the underlying mechanisms. Intraperitoneal administration of asarinin to mice with pulmonary fibrosis showed that asarinin effectively attenuated pulmonary fibrosis, and this effect was significantly inhibited by the PPARγ inhibitor GW9662. Asarinin inhibited TGF-β1-induced fibroblast-to-myofibroblast transition in vitro, while GW9662 and PPARγ gene silencing significantly inhibited this effect. In addition, asarinin inhibited not only the canonical Smad pathway of TGF-β but also the non-canonical AKT and MAPK pathways by activating PPARγ. Our study demonstrates that asarinin can be used as a therapeutic agent for pulmonary fibrosis, and that PPARγ is its key target.

Topics: Animals; Bleomycin; Idiopathic Pulmonary Fibrosis; Lignans; Mice; PPAR gamma

Vascular endothelial cells produce vasoactive substances, such as nitric oxide (NO), to regulate vascular relaxation and contraction. Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) enhance NO production in endothelial cells, and sesamin, a sesame lignan contained in sesame seeds, also promotes NO production. This study examined DHA, EPA, and sesamin's combined effects since it was expected that combining them would further enhance NO production in endothelial cells. Using a human umbilical vein endothelial cell (HUVEC), the NO amount secreted in the culture supernatant was analyzed. Sesamin metabolite (SC1) was used in the experiments because it is a major metabolite in human blood after sesamin absorption. When cells were treated with DHA or EPA alone, they increased NO production in a concentration-dependent manner, whereas no change in NO production was observed for SC1. NO production increased when DHA and EPA were treated in combination with SC1, although the low DHA and EPA concentrations showed no difference in NO production. In the concentrations in which the combined effect was observed, SC1 activated eNOS via calcium signaling, whereas DHA and EPA activated eNOS via alterations in the membrane lipid environment. The combined effect of the two pathways was considered to have enhanced the eNOS activity. These results suggested that combining DHA, EPA, and sesamin might improve vascular endothelial function.

Topics: Docosahexaenoic Acids; Eicosapentaenoic Acid; Human Umbilical Vein Endothelial Cells; Humans; Lignans; Sesamum

Diabetes is a chronic metabolic disease characterized by improperly regulating proteins, carbohydrates, and lipids due to insulin deficiency or resistance. The increasing prevalence of diabetes poses a tremendous socioeconomic burden worldwide, resulting in the rise of many studies on Chinese herbal medicines to discover the most effective cure for diabetes. Sesame seeds are among these Chinese herbal medicines that were found to contain various pharmacological activities, including antioxidant and anti-inflammatory properties, lowering cholesterol, improving liver function, blood pressure and sugar lowering, regulating lipid synthesis, and anticancer activities. These medicinal benefits are attributed to sesamin, which is the main lignan found in sesame seeds and oil. In this study, Wistar rat models were induced with type 2 diabetes using streptozotocin (STZ) and nicotinamide, and the effect of sesamin on the changes in body weight, blood sugar level, glycosylated hemoglobin (HbA1c), insulin levels, and the states of the pancreas and liver of the rats were evaluated. The results indicate a reduced blood glucose level, HbA1c, TG, and ALT and AST enzymes after sesamin treatment, while increased insulin level, SOD, CAT, and GPx activities were also observed. These findings prove sesamin's efficacy in ameliorating the symptoms of diabetes through its potent pharmacological activities.

Topics: Animals; Diabetes Mellitus, Type 2; Dioxoles; Glycated Hemoglobin; Insulin; Lignans; Plant Extracts; Rats; Rats, Wistar

Topics: Benzodioxoles; Dioxoles; Humans; Lignans; Melanoma; Phenols

The progression of chronic kidney disease (CKD) increases the risks of cardiovascular morbidity and end-stage kidney disease. Indoxyl sulfate (IS), which is derived from dietary l-tryptophan by the action of bacterial l-tryptophan indole-lyase (TIL) in the gut, serves as a uremic toxin that exacerbates CKD-related kidney disorder. A mouse model previously showed that inhibition of TIL by 2-aza-l-tyrosine effectively reduced the plasma IS level, causing the recovery of renal damage. In this study, we found that (+)-sesamin and related lignans, which occur abundantly in sesame seeds, inhibit intestinal bacteria TILs. Kinetic studies revealed that (+)-sesamin and sesamol competitively inhibited Escherichia coli TIL (EcTIL) with K

Topics: Benzodioxoles; Dioxoles; Enzyme Inhibitors; Gastrointestinal Microbiome; Kinetics; Lignans; Molecular Docking Simulation; Phenols; Renal Insufficiency, Chronic; Sesamum; Tryptophanase

Diabetic retinopathy (DR) is the most common microvascular complication in diabetes and the leading cause of vision loss and blindness globally. Due to the unsatisfied outcome of current therapies, a novel strategy needs to be developed. BV2 microglial cells were treated with 25 natural compounds, respectively, stimulated by high glucose (HG) to screen for a potential candidate drug. Streptozotocin (STZ)-induced diabetic mice were injected with different doses of the candidate sesamin every 2 days for 1 mo. Then, its protective role and possible mechanism were evaluated. Sesamin was selected as the candidate drug due to its inhibition on the secretion of tumor necrosis factor-α (TNFα) in the screen assay. Sesamin also dose-dependently inhibited mRNA levels of HG-induced inflammatory cytokines, including TNFα, interleukin (IL)-1β, and IL-6, activated NF-κB signaling pathway, and reduced oxidative stress by decreasing reactive oxygen species levels and increasing antioxidant enzymes in the BV2 and primary retinal microglia. In addition, sesamin alleviated brain-retinal barrier breakdown by Evans blue leakage assay and reduced inflammation in streptozotocin-induced diabetic mice. In conclusion, sesamin effectively inhibits HG-induced microglial inflammation in the retina both in vivo and in vitro, suggesting that sesamin might serve as a candidate drug for DR treatment.

Topics: Animals; Anti-Inflammatory Agents; Cytokines; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Dioxoles; Inflammation; Lignans; Male; Mice; Microglia

Sesamin and episesamin are the main lignans found in refined sesame oil and have been reported to exert various health benefits. However, the health benefits of these lignans and their molecular mechanisms have not been fully understood. This study evaluated the effects of sesamin, episesamin, and their metabolites on the nuclear bile acid receptor, farnesoid X receptor (FXR, NR1H4), which regulate gene expression involved in bile acid metabolism and gluconeogenesis. By using two different cell-based luciferase reporter assay systems, we found that sesamin, sesamin metabolites, and some episesamin metabolites inhibited FXR activation driven by a bile acid and a synthesized agonist, and it is suggested that these compounds exert their antagonist activity by competing with the FXR agonists on the ligand-binding domain. Sesamin and its major metabolite SC-1 suppressed the expression of several gluconeogenesis-related genes governed by FXR in HepG2 cells but did not affect the expression level of CYP7A1, the rate-limiting enzyme for bile acid synthesis. Dietary sesamin supplementation (AIN-93G supplemented with 0.5% sesamin) led to the decreased hepatic expression of several gluconeogenesis-related genes and reduced blood glucose levels in mice, without adverse effects on bile acid metabolism. These results shed light on the health benefits of taking sesamin and episesamin.

Topics: Animals; Dioxoles; Gluconeogenesis; Lignans; Liver; Mice

Non-alcoholic fatty liver disease (NAFLD) can be attributed to the imbalance between lipogenesis and lipidolysis in the liver. Sesame lignans (sesamin, sesamolin, and sesamol) are unique bioactive compounds responsible for the nutritional function of sesame oils. However, the preventive effects of three lignans on oxidative stress and lipid metabolism in steatosis HepG2 cells have not been compared. In this study, we investigated the role of sesamin, sesamolin, and sesamol on hepatic lipid accumulation and explored the underlying mechanism via a well-established cell model. The results showed that 3 μg/ml of lignans could decrease the TG/TC contents and alleviate cellular oxidative stress, with an order of the lipid-lowering effect as sesamol > sesamin > sesamolin. The lignan-activated AMPK and PPAR signaling pathways enhanced gene and protein expressions related to fatty acid oxidation, cholesterol efflux, and catabolism. Meanwhile, treatment of the steatosis HepG2 cells with sesamin, sesamolin, and sesamol reduced lipid synthesis and cholesterol uptake, thus lowering intracellular lipogenesis in the process of NAFLD. Our data suggested that sesame lignans can attenuate oxidative stress and regulate lipid metabolism in liver cells, which may be potential therapeutic agents for treating the NAFLD. PRACTICAL APPLICATIONS: The present work demonstrated that sesame lignans can be used for dietary supplements or functional additives with excellent lipid-lowering effects. Furthermore, this study supplied potential molecular mechanisms involved in NAFLD treatment process, and also provided nutritional guidelines for sesame oil evaluation and selection.

Topics: Benzodioxoles; Cholesterol; Dioxoles; Hep G2 Cells; Humans; Lignans; Lipid Metabolism; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Phenols; Sesame Oil; Sesamum

Topics: Animals; Apoptosis; Asthma; Bronchoalveolar Lavage Fluid; Cytokines; Dioxoles; Humans; Inflammation; Interleukin-4; Lignans; Lung; Mice; Mitochondria; Mitophagy; Protein Kinases; Tumor Necrosis Factor-alpha; Ubiquitin-Protein Ligases

Lead (Pb) is one of the most hazardous pollutants that induce a wide spectrum of neurological changes such as learning and memory deficits. Sesamin, a phytonutrient of the lignan class, exhibits anti-inflammatory, anti-apoptotic, and neuroprotective properties. The present study was designed to investigate the effects of sesamin against Pb-induced learning and memory deficits, disruption of hippocampal theta and gamma rhythms, inflammatory response, inhibition of blood δ-aminolevulinic acid dehydratase (δ-ALA-D) activity, Pb accumulation, and neuronal loss in rats.. Sesamin treatment (30 mg/kg/day; P.O.) was started simultaneously with Pb acetate exposure (500 ppm in standard drinking water) in rats, and they continued for eight consecutive weeks.. The results showed that chronic exposure to Pb disrupted the learning and memory functions in both passive-avoidance and water-maze tests, which was accompanied by increase in spectral theta power and theta/gamma ratio, and a decrease in spectral gamma power in the hippocampus. Additionally, Pb exposure resulted in an enhanced tumor necrosis factor-alpha (TNF-α) content, decreased interleukin-10 (IL-10) production, inhibited blood δ-ALA-D activity, increased Pb accumulation, and neuronal loss of rats. In contrast, sesamin treatment improved all the above-mentioned Pb-induced pathological changes.. This data suggests that sesamin could improve Pb-induced learning and memory deficits, possibly through amelioration of hippocampal theta and gamma rhythms, modulation of inflammatory status, restoration of the blood δ-ALA-D activity, reduction of Pb accumulation in the blood and the brain tissues, and prevention of neuronal loss.

Topics: Animals; Dioxoles; Gamma Rhythm; Hippocampus; Lead; Lignans; Maze Learning; Memory Disorders; Rats

Osteoporotic fracture has been regarded as one of the most common bone disorders in the aging society. The natural herb-derived small molecules were revealed as potential treatment approaches for osteoporotic fracture healing. Sesamin is a member of lignan family, which possesses estrogenic activity and plays a significant role in modulating bone homeostasis. Our previous study reported the promoting effect of sesamin on postmenopausal osteoporosis treatment. However, the role of sesamin in osteoporotic fracture healing has not been well studied yet. In this study, we further investigated the putative treatment effect of sesamin on osteoporotic fracture healing. Our study indicated that sesamin could activate bone morphogenetic protein 2 (BMP2) signaling pathway and further promotes in vitro chondrogenesis and angiogenesis activities. This promoting effect was abolished by the treatment of ERα inhibitor. In the osteoporotic bone fracture model, we demonstrated that sesamin markedly improves the callus formation and increases the cartilaginous area at the early-stage, as well as narrowing the fracture gap, and expands callus volume at the late-stage fracture healing site of the OVX mice femur. Furthermore, the angiogenesis at the osteoporotic fracture site was also significantly improved by sesamin treatment. In conclusion, our research illustrated the therapeutic potential and underlying regulation mechanisms of sesamin on osteoporotic fracture healing. Our studies shed light on developing herb-derived bioactive compounds as novel drugs for the treatment of osteoporotic fracture healing, especially for postmenopausal women with low estrogen level.

Topics: Animals; Chondrogenesis; Dioxoles; Female; Fracture Healing; Humans; Lignans; Mice; Osteoporotic Fractures; Rats; Rats, Sprague-Dawley

Lignans are plant-derived compounds that act as partial estrogen agonists. Chondroitin sulfate proteoglycans (CSPGs) represent one of the major components of the extracellular matrix. Here we aimed to understand the role of sesamin (SES), a major lignan compound, in the biosynthesis and degradation of CSPGs in the mouse hippocampus because CSPGs play a key role in the regulation of cognitive functions through the promotion of adult neurogenesis. The expression of the pro-inflammatory cytokine interleukin-1β was decreased by SES administration in the hippocampus of lipopolysaccharide (LPS)-treated mice, a model of neuroinflammation-induced cognitive deficits. The expression of genes related to biosynthesis and degradation of CSPGs in the hippocampus of LPS-treated mice was both increased and decreased by SES administration. Further, the diffuse extracellular matrix labeling of CSPGs by Wisteria floribunda agglutinin (WFA) in the hippocampus of LPS-treated mice was increased by SES administration. The densities of neural stem cells, late transit-amplifying cells, and newborn-granule cells in the hippocampus of LPS-treated mice were also increased by SES administration. Moreover, SES-induced alterations in gene expression, WFA labeling, and adult neurogenesis in LPS-treated mice were more evident in the dorsal hippocampus (center of cognition) than in the ventral hippocampus (center of emotion). Neither LPS nor SES administration affected locomotor activity, anxiety-like behavior, and depression-related behavior. However, impairments in contextual memory and sensorimotor gating in LPS-treated mice were recovered by SES administration. Our results show that SES can promote adult hippocampal neurogenesis through the upregulation of CSPGs, which may alleviate cognitive deficits induced by neuroinflammation.

Topics: Animals; Chondroitin Sulfate Proteoglycans; Chondroitin Sulfates; Cognition; Dioxoles; Disease Models, Animal; Hippocampus; Lignans; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Neuroinflammatory Diseases; Up-Regulation

Diabetes mellitus (DM), one of the principal causes of morbidity and mortality worldwide, is implicated in the progression of age-related neurodegenerative diseases (NDDs), in which microglial activation is a crucial mediator. Sesamin, a kind of phytochemical, shows inhibitory effects on microglial activation. The present study studied whether sesamin protects against neurotoxicity triggered by high glucose-induced microglial activation. We firstly demonstrated that high doses of glucose, which mimics hyperglycemia in DM, did induce the activation of murine BV2 microglial cells, increasing inflammatory responses such as the production of ROS or inflammatory mediators like IL-1β, TNF-⍺, and nitric oxide, through activation of p38 and JNK signaling pathways. Next, conditioned medium (CM) collected from high glucose-activated BV2 cell culture was used to show aggravated neurotoxicity in differentiated PC12 cells, indicating that high glucose-activated microglia could induce neurotoxicity. Interestingly, pretreatment of BV2 cells with sesamin diminished high glucose-induced microglia activation and inflammatory responses. Moreover, neurotoxicity in PC12 cells was found to be decreased in the group treated with CM from the sesamin-pretreated BV2 cell culture, suggesting sesamin inhibited microglial activation, thereby protecting neurons from activated microglia-mediated neurotoxicity. Thus, sesamin might be a potential compound to use in the prevention of diabetic-induced NDDs.

Topics: Animals; Culture Media, Conditioned; Dioxoles; Glucose; Lignans; MAP Kinase Signaling System; Mice; Microglia; Neurotoxicity Syndromes; Rats

Lung damage can be caused by fine particulate matter (PM

Topics: Animals; Apoptosis; Autophagy; Dioxoles; Inflammation; Lignans; Lung; Lung Injury; Oxidative Stress; Particulate Matter; Rats; Rats, Sprague-Dawley

Topics: Animals; Cell Line, Tumor; Colorectal Neoplasms; Dioxoles; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Lignans; Mice; Mice, Nude; Neovascularization, Pathologic; NF-kappa B; Signal Transduction; Vascular Endothelial Growth Factor A

Cyclophosphamide is an anticancer drug with a wide spectrum of clinical uses, but its typical side effects are multiple complications, including nephron toxicity. The possible molecular mechanism of the nephroprotective action of sesamin (SM) against cyclophosphamide (CP) induced renal toxicity was investigated in rats by understanding oxidative stress and inflammatory cytokines. In this study, rats were arbitrarily grouped into the following four groups: a normal control group (CNT); a CP-induced toxicity group; a treatment group with two doses of sesamin SM10 and SM20; a group with sesamin (SM20) alone. A single dose of CP (150 mg/kg body, i.p.) was administered on day 4 of the experiments, while treatment with SM was given orally for seven days from day 1. The group treated with SM showed a significant protective effect against CP-induced renal damage in rats. Treatment with SM significantly increased the antioxidant enzymes (GSH, CAT, and SOD) and reduced malondialdehyde (MDA) levels. Thus, SM significantly overcame the elevated kidney function markers (creatinine, blood urea nitrogen, and uric acid) by attenuating oxidative stress. The SM also significantly reduced the elevated cytokines (IL-1β and TNFα) and caspase-3 in the treated group. Histopathological studies confirmed the protective effect of sesamin (SM) on CP-induced nephrotoxicity. In conclusion, the current findings support the nephroprotective effect of sesamin against CP-induced renal injury.

Topics: Animals; Antineoplastic Agents; Antioxidants; Apoptosis; Caspase 3; Creatinine; Cyclophosphamide; Cytokines; Dioxoles; Kidney; Lignans; Malondialdehyde; Oxidative Stress; Rats; Renal Insufficiency; Superoxide Dismutase; Tumor Necrosis Factor-alpha; Uric Acid

Tripartite motif-containing 44 (TRIM44) is known to play an oncogenic role in multiple human cancers, including esophageal cancer. Sesamin possesses potent anti-inflammatory and anti-cancer properties for various cancers. This study is designed to unravel the biological functions of sesamin and TRIM44 in esophageal cancer. TRIM44 expression in esophageal squamous cell cancer (ESCC) cell lines and tissues was determined by RT-qPCR assay and Western blot. The effects of sesamin and TRIM44 on ESCC cell growth in vivo and in vitro were assessed by the mouse model and CCK-8 assay, respectively. We found that TRIM44 was significantly upregulated in ESCC cell lines and tissues when compared to their counterparts. Sesamin treatment or depletion of TRIM44 markedly reduced ESCC cell proliferation. The nuclear factor kappa B (NF-κB) and toll-like receptor 4 (TLR4) signaling pathway may be involved in sesamin-mediated TRIM44 suppression. Finally, we showed that oral administration of sesamin dramatically inhibited tumor growth or ESCC in nude mice. Our results suggest that sesamin exerts anti-tumor activity in ESCC via inhibition of NF-κB signaling pathway, demonstrating its potential for the treatment of esophageal cancer.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Cell Survival; Dioxoles; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Humans; Intracellular Signaling Peptides and Proteins; Lignans; Mice; Mice, Nude; NF-kappa B; Signal Transduction; Transplantation, Heterologous; Tripartite Motif Proteins

Allogeneic hematopoietic stem cell transplantation (HSCT) remains the key for the treatment of malignant hematological diseases, and acute graft-versus-host disease (aGVHD) that might occur after allogenic transplantation can be life threatening and promote disease recurrence. GVHD damages the various parts of the body by upregulating T helper 1 cytokines (Th1) cytokines and stimulating CD4、CD8 + T cells. GVHD can exhibit significant immunoregulatory effects, but could be easily affected by the mesenchymal stem cells (MSC) environment, and hence the MSC immunosuppressive effects on GVHD remain unpredictable. Hence, to better understand the role of MSC in the prevention and treatment of GVHD, umbilical cord derived mesenchymal stem cells (UC-MSC) were pre-treated with Chinese medicine Asarinin and IFN-γ. In the mix lymphocyte reaction, we found that Asarinin pre-treated UC-MSC can exert significantly greater inhibition towards the proliferation of CD4 and CD8 + T cells, down-regulate Th1 type cytokines, up-regulate Th2 type cytokines, and reduce the inflammatory damage to liver, lung and intestine of aGVHD mice model. Moreover, Asarinin can cooperate with IFN-γto promote UC-MSC to secrete indoleamine 2,3-dioxygenase (IDO). Our findings establish that Asarinin pre-treated UC-MSC can significantly promote the immunosuppressive effects of MSC on aGVHD after hematopoietic stem cell transplantation.

Topics: Animals; Cells, Cultured; Cytokines; Dioxoles; Disease Models, Animal; Drugs, Chinese Herbal; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Lignans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Primary Cell Culture; Transplantation, Homologous; Umbilical Cord

Sesamin is a lignan compound in plants that has various pharmacological effects, including reducing diabetes-associated injuries, regulating fatty acid and cholesterol metabolism, and exerting antiinflammatory and antitumour effects. Previous studies have reported that sesamin can inhibit the proliferation of several types of tumour cells and exert antitumour effects. However, the antitumour effect of sesamin on T-cell lymphoma is still unknown. In this study, we selected a T-cell lymphoma mouse model to investigate the mechanism of sesamin against T-cell lymphoma via programmed cell death in vivo and in vitro. We found that sesamin could significantly inhibit the growth of EL4 cells in a tumour-bearing mouse model. Sesamin markedly inhibited the proliferation of EL4 cells by inducing apoptosis, pyroptosis and autophagy. Autophagy occurred earlier than apoptosis and pyroptosis in EL4 cells after sesamin treatment. Blocking autophagy inhibited apoptosis and pyroptosis in EL4 cells after sesamin treatment. Taken together, these results suggested that sesamin promoted apoptosis and pyroptosis via autophagy to enhance antitumour effects on murine T-cell lymphoma. This study expands our knowledge of the pharmacological effects of sesamin on T-cell lymphoma, and provides a theoretical basis for the development of new antitumour drugs and treatments for T-cell lymphoma.

Topics: Animals; Antineoplastic Agents; Apoptosis; Autophagy; Cell Line, Tumor; Cell Proliferation; Dioxoles; Disease Models, Animal; Female; Lignans; Lymphoma, T-Cell; Mice, Inbred BALB C; Phytotherapy; Pyroptosis; Stimulation, Chemical

Epidemic modeling has been a key tool for understanding the impact of global viral outbreaks for over two decades. Recent developments of the COVID-19 pandemic have accelerated research using compartmental models, like SI, SIR, SEIR, with their appropriate modifications. However, there is a large body of recent research consolidated on homogeneous population mixing models, which are known to offer reduced tractability, and render conclusions hard to quantify. As such, based on our recent work, introducing the heterogeneous geo-spatial mobility population model (GPM), we adapt a modified SIR-V (susceptible-infected-recovered-vaccinated) epidemic model which embodies the idea of patient relapse from R back to S, vaccination of R and S patients (reducing their infectiousness), thus altering the infectiousness of V patients (from

Topics: Acute Lung Injury; Adherens Junctions; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antigens, CD; Antineoplastic Agents, Phytogenic; Antioxidants; Apoptosis; beta Catenin; Brain Ischemia; Cadherins; Carcinogenesis; Catalysis; Cell Line; Cells, Cultured; Curcuma; Curcumin; Dioxoles; Disease Models, Animal; Endothelial Cells; Epithelial Cells; Heme Oxygenase (Decyclizing); Humans; Inflammasomes; Intestinal Diseases; Intestinal Mucosa; Ischemic Stroke; Kidney Neoplasms; Lignans; Lung; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microglia; NAD(P)H Dehydrogenase (Quinone); Nanostructures; NF-E2-Related Factor 2; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Phosphatidylinositol 3-Kinases; Phytotherapy; Plant Extracts; Pneumonia; PPAR gamma; Proto-Oncogene Proteins c-akt; Pyroptosis; Rats; Rats, Sprague-Dawley; Rats, Wistar; Reperfusion Injury; Respiratory Distress Syndrome; Sepsis; Sesamum; Signal Transduction; Silybin; Silybum marianum; Silymarin; Sirtuin 3; Titanium; Transfection; Treatment Outcome; White Matter

Topics: Animals; Antioxidants; Cardiovascular Diseases; Dioxoles; Disease Models, Animal; Ferroptosis; Lignans; Particulate Matter; Rats; Rats, Sprague-Dawley

As one of the leading causes of bone fracture in postmenopausal women and in older men, osteoporosis worldwide is attracting more attention in recent decades. Osteoporosis is a common disease mainly resulting from an imbalance of bone formation and bone resorption. Pharmaceutically active compounds that both activate osteogenesis, while repressing osteoclastogenesis hold the potential of being therapeutic medications for osteoporosis treatment. In the present study, sesamin, a bioactive ingredient derived from the seed of Sesamum Indicum, was screened out from a bioactive compound library and shown to exhibit dual-regulating functions on these two processes. Sesamin was demonstrated to promote osteogenesis by upregulating Wnt/β-catenin, while repressing osteoclastogenesis via downregulating NF-κB signaling . Furthermore, DANCR was found to be the key regulator in sesamin-mediated bone formation and resorption . In an ovariectomy (OVX)-induced osteoporotic mouse model, sesamin could rescue OVX-induced bone loss and impairment. The increased serum level of DANCR caused by OVX was also downregulated upon sesamin treatment. In conclusion, our results demonstrate that sesamin plays a dual-functional role in both osteogenesis activation and osteoclastogenesis de-activation in a DANCR-dependent manner, suggesting that it may be a possible medication candidate for osteoporotic patients with elevated DNACR expression levels.

Topics: Animals; beta Catenin; Bone Resorption; Cell Differentiation; Dioxoles; Female; HEK293 Cells; Humans; Lignans; Mesenchymal Stem Cells; Mice; Mice, Inbred C57BL; NF-kappa B; Osteoblasts; Osteoclasts; Osteogenesis; Osteoporosis, Postmenopausal; RANK Ligand; RAW 264.7 Cells; RNA, Long Noncoding; Wnt Signaling Pathway

Asarinin, β-eudesmol, and wogonin have common antiangiogenic activities and have the potential for use in chemotherapy. Besides, they are multivalent substances that are combined in various herbal medicines. The purpose of this study was to develop a method for simultaneous analysis of asarinin, β-eudesmol, and wogonin, which are representative pharmacological components of Asarum heterotropoides, Atractylodes lancea, and Scutellaria baicalensis, respectively, in rat biosamples using ultraperformance liquid chromatography-tandem mass spectrometry. The three components were separated using 5 mm aqueous ammonium acetate containing 0.1% formic acid and acetonitrile as a mobile phase, equipped with a KINETEX core-shell C

Topics: Animals; Chromatography, High Pressure Liquid; Dioxoles; Flavanones; Lignans; Linear Models; Male; Plant Extracts; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Sensitivity and Specificity; Sesquiterpenes, Eudesmane; Tandem Mass Spectrometry

Topics: Alternative Splicing; Anticholesteremic Agents; Antihypertensive Agents; Antioxidants; Aristolochic Acids; Asarum; Biosynthetic Pathways; Dioxoles; Gene Expression Profiling; Gene Expression Regulation, Plant; Lignans; Microsatellite Repeats; Plant Breeding; Plant Leaves; Plant Roots; Plants, Medicinal; RNA, Long Noncoding; Transcriptome

Neuroinflammation and loss of neurotrophic support have key roles in the pathophysiology of diabetes-associated behavioral deficits (DABD). Sesamin (Ses), a major lignan of sesame seed and its oil, shows anti-hyperglycemic, anti-oxidative, and neuroprotective effects. The present study was designed to assess the potential protective effects of Ses against DABD and investigate the roles of inflammatory markers and neurotrophic factors in streptozotocin (STZ)-induced diabetic rats. After confirmation of diabetes, Ses (30 mg/kg/day; P.O.) or insulin (6 IU/rat/day; S.C.) was administered to rats for eight consecutive weeks. During the eighth-week period of the study, behavioral functions of the animals were evaluated by employing standard behavioral paradigms. Moreover, inflammation status, neurotrophic factors, and histological changes were assessed in the cerebral cortex and hippocampal regions of the rats. The results of behavioral tests showed that STZ-induced diabetes increased anxiety-/depression-like behaviors, decreased locomotor/exploratory activities, and impaired passive avoidance learning and memory. These DABD were accompanied by neuroinflammation, lack of neurotrophic support, and neuronal loss in both cerebral cortex and hippocampus of the rats. Intriguingly, chronic treatment with Ses improved all the above-mentioned diabetes-related behavioral, biochemical, and histological deficits, and in some cases, it was even more effective than insulin therapy. In conclusion, the results suggest that Ses was capable of improving DABD, which might be ascribed, at least partly, to the reduction of blood glucose level, inhibition of neuroinflammation, and potentiation of neurotrophic factors.

Topics: Animals; Antioxidants; Anxiety; Cerebral Cortex; Depression; Diabetes Mellitus, Experimental; Dioxoles; Disease Models, Animal; Hippocampus; Inflammation; Lignans; Male; Maze Learning; Memory Disorders; Nerve Growth Factors; Neuroprotective Agents; Rats

To investigate the protective effects and mechanisms of sesamin (SES) on dextran sulfate sodium (DSS)-induced experimental colitis in mice.. SES (50, 100, and 200 mg kg-1) were orally administered to C57BL/6 male mice after DSS instillation. The anti-inflammatory effect of SES on colonic damage was assessed by clinical, macroscopic, microscopic, and inflammatory signaling pathways.. It could be found that bodyweight and colon length of mice treated with DSS was significantly decreased while that were increased by SES treatment. SES treatment reduced the DAI values and improved the histopathology of the colon in the DSS-treated mice. SES also reduced TNF-α, IL-1β and IL-6 production caused by DSS. We also measured the expression of the phosphorylation of p65, IκB, p38, ERK and JNK protein and found that SES can alleviate colon damage via the NF-κB and MAPK signaling pathways. The findings of this study suggested that SES had anti-inflammatory effects on intestinal inflammation and can be used as a new therapeutic candidate for inflammatory bowel disease.

Topics: Animals; Anti-Inflammatory Agents; Colitis; Colon; Dextran Sulfate; Dioxoles; Lignans; Male; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; NF-kappa B; Protective Agents

Sesamin, a lignan compound, exhibits a variety of biological activities and possesses potent anticancer properties on some human cancers. However, its effect on human colorectal cancer (CRC) remains to be elucidated. To investigate the effects of sesamin on CRC cells and further to explore the mechanisms, cell viability, cell cycle and apoptosis assays were performed in this study. We found that sesamin had a selective antiproliferation of CRC cell line HCT116 in a dose- and time-dependent manner, but no obvious effect on human normal colorectal mucosa epithelial cell FHC. Further study showed that sesamin-induced cell cycle arrest and decreased the expression of Cyclin D1 significantly and dose-dependently in HCT116 cells. Moreover, sesamin dose-dependently triggered apoptosis of HCT116 but not FHC, and promoted the expression levels of proapoptotic biomarkers Bax, cleaved caspase-3 and cleaved PARP-1 and inhibited the expression of antiapoptotic biomarker Bcl-2. Western blot analysis was used to reveal the possible signaling pathways, and we found that sesamin upregulated the phosphorylation expression levels of C-Jun N-terminal kinase (JNK) and p38 except ERK1/2 in a dose-dependent way in both HCT116 and another CRC cell line SW480. Moreover, we found that the apoptosis effect induced by sesamin was partially eliminated by inhibiting JNK or p38 activation. Finally, we showed that sesamin effectively reduced the growth of xenograft tumors derived from cell lines with limited toxicity. Taken together, the potential ability of sesamin to induce cell cycle arrest and apoptosis was shown to be via the p38 and JNK mitogen-activated protein kinase signaling pathways, which may be one of the mechanisms of the anticancer activity of this low-toxic agent.

Topics: Animals; Antioxidants; Apoptosis; Cell Cycle; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Survival; Colorectal Neoplasms; Cyclin D1; Dioxoles; Dose-Response Relationship, Drug; Humans; JNK Mitogen-Activated Protein Kinases; Lignans; Mice; Mice, Inbred BALB C; p38 Mitogen-Activated Protein Kinases; Signal Transduction; Time Factors; Up-Regulation

The effect of sesamin on intestinal flora was studied by in vitro animal fecal anaerobic fermentation system, and were analyzed by 16S rDNA sequencing. Results showed that sesamin modulated the composition of intestinal microorganisms and reshaped gut microbiome. The abundance of probiotics Lactobacillaceae and Bifidobacteriaceae increased, while the abundance of Enterobacteriaceae decreased. The properties of probiotics (Bifidobacterium bifidum and Lactophilus acidophilus) adhesion to epithelial colon cells (NCM460) were assessed by gram staining and plate counting methods. Results showed that sesamin increased the adhesive index of probiotics. Analysis of RT-qPCR, Western blot and immunofluorescence staining indicated that sesamin up-regulated the expression of the adhesive protein (β-cadherin and E-cadherin) of NCM460 cells. In conclusion, sesamin could promote the proliferation and adhesion of intestinal probiotics leading to modulating gut microbiota, which provided basis for sesamin as a food-borne functional factor for improving intestinal health.

Topics: Animals; Bacterial Adhesion; Bacterial Proteins; Bifidobacterium bifidum; Cell Line; Dioxoles; Dose-Response Relationship, Drug; Epithelial Cells; Feces; Gastrointestinal Microbiome; Gene Expression Regulation, Bacterial; Humans; Intestinal Mucosa; Lactobacillus acidophilus; Lignans; Rats; Rats, Sprague-Dawley; RNA, Messenger

Topics: Angiogenesis Inhibitors; Animals; Caprifoliaceae; Cell Cycle Checkpoints; Dioxoles; Human Umbilical Vein Endothelial Cells; Humans; Lignans; Medicine, Tibetan Traditional; Molecular Structure; Phytochemicals; Tibet; Zebrafish

Neuroinflammation-mediated microglial reactivity is a major process, which explains the increased risk of Alzheimer's disease (AD) development in patients with Type 2 diabetes mellitus (T2DM). Advanced glycation end products (AGEs), formed by hyperglycemic condition in diabetes, is characterized as an intermediary of brain injury with diabetes through induction of microglial reactivity. Here, we explored the effect of AGEs on microglial reactivity using BV2 as a model. The NF-κB, p38 and JNK pathways were found to be important mechanism in AGEs-induced BV2 microglial reactivity. NF-κB inhibitor (BAY-11-7082), p38 inhibitor (SB203580) and JNK inhibitor (SP600125) exhibited the potential inhibition of AGEs-induced NO production. We also found that the sesamin, a major lignan found in sesame seed oils, exerts an anti-inflammatory effect under AGEs-induced microglial reactivity via suppressing the phosphorylation of NF-κB, p38 and JNK pathways. Moreover, sesamin also ameliorated AGEs-induced-receptor for advanced glycation end products (RAGE) expression. Taken together, sesamin may be a promising phytochemical compound to delay inflammatory progress by AGEs microglia function. Similarly, inhibition of AGEs-induced microglial reactivity might be potential therapeutic targets of neuroinflammation-based mechanisms in T2DM link progressive AD.

Topics: Animals; Antioxidants; Cell Line; Dioxoles; Glycation End Products, Advanced; Lignans; Mice; Microglia; Neuroprotective Agents; NF-kappa B; Phosphorylation; Signal Transduction

Intervertebral disc degeneration-related diseases are common health problems in the department of orthopedics. However, there is no effective treatment protecting the intervertebral disc from degeneration. Sesamin, a kind of sesame lignans extracted from sesame seed oil, has been proved to inhibit lipopolysaccharide-induced inflammation and extracellular matrix catabolism in rat intervertebral disc in vitro and ex vivo. The present study was designed to investigate the effects of sesamin on lesion-induced intervertebral disc degeneration in vivo. Degeneration of rat tail disc was induced by puncture lesion, followed by intradiscal injection of sesamin. Magnetic resonance imaging (MRI), quantitative real-time polymerase chain reaction, histological analysis, and biochemical analysis were carried out to analyze degeneration progression 2 weeks after surgery. As shown by results, intradiscal injection of sesamin inhibited the MRI signal decrease of nucleus pulposus (NP) in T2-weighted images. The upregulated mRNA expression of MMP-3 and ADAMTS-5 induced by lesion was significantly suppressed by sesamin injection. Sesamin partly protected mRNA expression of Col2a1 and Acan from downregulation. Intradiscal injection of sesamin effectively maintained the normal morphology of disc and inhibited lesion-induced degeneration-related histological changes. Immunohistochemical assay demonstrated that the upregulation of degradative enzymes protein expression and the downregulation of type II collagen expression in NP were suppressed by sesamin. According to biochemical analysis, sesamin significantly inhibited the lesion-induced decrease of proteoglycan content in NP. The present study proved the protective effects of sesamin on lesion-induced intervertebral disc degeneration at an early stage.

Topics: Animals; Dioxoles; Disease Models, Animal; DNA; Extracellular Matrix; Gene Expression Regulation; Intervertebral Disc; Intervertebral Disc Degeneration; Lignans; Magnetic Resonance Imaging; Nucleus Pulposus; Proteoglycans; Rats, Sprague-Dawley; RNA, Messenger

Sesame (Sesamum indicum) seeds contain a large number of lignans, phenylpropanoid-related plant specialized metabolites. (+)-Sesamin and (+)-sesamolin are major hydrophobic lignans, whereas (+)-sesaminol primarily accumulates as a water-soluble sesaminol triglucoside (STG) with a sugar chain branched via β1→2 and β1→6-O-glucosidic linkages [i.e. (+)-sesaminol 2-O-β-d-glucosyl-(1→2)-O-β-d-glucoside-(1→6)-O-β-d-glucoside]. We previously reported that the 2-O-glucosylation of (+)-sesaminol aglycon and β1→6-O-glucosylation of (+)-sesaminol 2-O-β-d-glucoside (SMG) are mediated by UDP-sugar-dependent glucosyltransferases (UGT), UGT71A9 and UGT94D1, respectively. Here we identified a distinct UGT, UGT94AG1, that specifically catalyzes the β1→2-O-glucosylation of SMG and (+)-sesaminol 2-O-β-d-glucosyl-(1→6)-O-β-d-glucoside [termed SDG(β1→6)]. UGT94AG1 was phylogenetically related to glycoside-specific glycosyltransferases (GGTs) and co-ordinately expressed with UGT71A9 and UGT94D1 in the seeds. The role of UGT94AG1 in STG biosynthesis was further confirmed by identification of a STG-deficient sesame mutant that predominantly accumulates SDG(β1→6) due to a destructive insertion in the coding sequence of UGT94AG1. We also identified UGT94AA2 as an alternative UGT potentially involved in sugar-sugar β1→6-O-glucosylation, in addition to UGT94D1, during STG biosynthesis. Yeast two-hybrid assays showed that UGT71A9, UGT94AG1, and UGT94AA2 were found to interact with a membrane-associated P450 enzyme, CYP81Q1 (piperitol/sesamin synthase), suggesting that these UGTs are components of a membrane-bound metabolon for STG biosynthesis. A comparison of kinetic parameters of these UGTs further suggested that the main β-O-glucosylation sequence of STG biosynthesis is β1→2-O-glucosylation of SMG by UGT94AG1 followed by UGT94AA2-mediated β1→6-O-glucosylation. These findings together establish the complete biosynthetic pathway of STG and shed light on the evolvability of regio-selectivity of sequential glucosylations catalyzed by GGTs.

Topics: Biosynthetic Pathways; Catalysis; Cytochrome P-450 Enzyme System; Dioxoles; Furans; Glucosides; Glucosyltransferases; Glycosyltransferases; Lignans; Phylogeny; Plant Proteins; Seeds; Sesamum

Sesame was one of the most important crops in Africa and east Asia. The sesamin and sesamolin in sesames have shown various pharmacological, biological and physiologic activities. In this study, a rapid and nondestructive method for determination of sesamin and sesamolin in Chinese sesames by near-infrared spectroscopy coupled with chemometric method was proposed. The near infrared spectra of sesame samples from three different Chinese areas were collected and the partial least squares (PLS) was used to construct the quantitative models. The spectral preprocessing and variable selection methods were adopted to improve the predictability and stability of the model. Reasonable quantitative results can be obtained when the samples used for model construction and prediction were harvested in same years. For sesamin and sesamolin, the correlation coefficient (R) and root mean square error prediction (RMSEP) were 0.9754, 0.9636 and 151.2951, 39.7720, respectively. The optimized models seem less effective when they were used to predict the samples harvested in other years or countries. However, acceptable results can still be obtained.

Topics: China; Dioxoles; Lignans; Sesamum; Spectroscopy, Near-Infrared

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with a disappointing prognosis. The aim of this study was to investigate the anticancer effect of sesamin and the underlying mechanism. The MTT assay was used to detect the proliferation of NSCLC cells. The cell cycle and apoptosis were analyzed by flow cytometry. The protein levels of Akt, p-Akt (Ser473), p53, cyclin D1, CDK2, MDM2, p-MDM2 (Ser166) were detected by western blotting. The expression of p-Akt (Ser473), p53 and Ki67 in vivo was analyzed by IHC. Histopathologic analyses of major organs (heart, liver, spleen, lung and kidney) were performed by H&E staining. The results show that sesamin suppressed cell proliferation and induced apoptosis of NSCLC cells (A549 and H1792) in a dose-dependent manner. Treatment with sesamin caused cell cycle arrest at G1 phase and inhibited cyclin D1 and CDK2 expression. In addition, sesamin inhibited Akt activity and upregulated p53 expression both in vivo and in vitro. When Akt and p53 were suppressed by LY294002 and PFTα, respectively, sesamin exerted no additional effects. The in vivo results mostly matched the in vitro findings. Specifically, sesamin exerted little damage to major organs. Taken together, this study demonstrates that sesamin suppresses NSCLC cell proliferation by induction of G1 phase cell cycle arrest and apoptosis via Akt/p53 pathway. Therefore, sesamin may be a promising adjuvant treatment for NSCLC therapy.

Topics: Animals; Apoptosis; Benzothiazoles; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Proliferation; Chromones; Dioxoles; Female; G1 Phase Cell Cycle Checkpoints; Humans; Lignans; Lung Neoplasms; Mice; Morpholines; Proto-Oncogene Proteins c-akt; Signal Transduction; Toluene; Tumor Suppressor Protein p53; Xenograft Model Antitumor Assays

Metabolism of lipids such as cholesterol and triglycerides has daily variations and is controlled by a circadian clock. Sesamin isomers, a mixture of sesamin and episesamin (SE), are types of lignans in sesame seed that have shown the improvement of lipid metabolism with various diseases in an animal model. We therefore tested whether the effects of SE on lipid metabolism are influenced by timing of administration. High-fat diet (HFD)-loaded rat was administered SE in the ZT13 or 14 (at the beginning of the active phase) or ZT23 or 22 (at the end of the active phase) every day for 7 or 28 days, and the effects on lipid metabolism were evaluated. The effects of SE were enhanced by duration-dependency: 28-day administration of SE strongly affected some parameters related to lipid metabolism, particularly cholesterol metabolism, as compared to 7-day administration. In particular, in 28-day administration, the analysis of serum and liver cholesterol levels revealed that SE administration decreases more effectively at the beginning of the active phase when compared to at the end of that. Furthermore, quantitative real-time polymerase chain reaction (QRT-PCR) and functional analysis indicated that suppression of cholesterol synthesis in the liver and promotion of cholesterol excretion from the liver, as well as inhibition of the functional activity and gene expression of sterol response element-binding protein 2 (Srebp2), which is a transcriptional factor and controls the gene expression involved in cholesterol-metabolism enzymes, contribute to enhancement of SE's effects at this administration timing. No significant differences were observed in triglyceride metabolism with regard to timing of SE administration. After 28-day administration of SE, administration at the beginning of the active phase only affected the expression of clock genes in the liver with phase-advance. In the pharmacokinetic study, administration time had no effect on the level of sesamin, episesamin or their metabolites in the liver after administration of SE for 28 days. The present results suggest that continuous long administration of SE at the beginning of the active phase is preferable for obtaining beneficial effects on lipid metabolism.

Topics: Animals; Circadian Rhythm; Dioxoles; Lignans; Lipid Metabolism; Liver; Rats; Rats, Sprague-Dawley

Nephrotoxicity of cisplatin (CP) involves renal oxidative stress and inflammation, and sesamin (a major liganin in many plants) has strong antioxidant and antiinflammatory actions. Therefore, we investigated here the possible mitigative action of sesamin on CP nephrotoxicity in rats. Sesamin was given orally (5 mg/kg/day, 10 days), and on the 7th day, some of the treated rats were injected intraperitoneally with either saline or CP (5 mg/kg). On the 11th day, rats were sacrificed, and blood and urine samples and kidneys were collected for biochemical estimation of several traditional and novel indices of renal damage in plasma and urine, several oxidative and nitrosative indices in kidneys, and assessment of histopathological renal damage. CP significantly and adversely altered all the physiological, biochemical and histopathological indices of renal function measured. Kidneys of CP-treated rats had a moderate degree of necrosis. This was markedly lessened when CP was given simultaneously with sesamin. Sesamin treatment did not significantly alter the renal CP concentration. The results suggested that sesamin had ameliorated CP nephrotoxicity in rats by reversing the CP-induced oxidative stress and inflammation. Pending further pharmacological and toxicological studies sesamin may be considered a potentially useful nephroprotective agent.

Topics: Animals; Antineoplastic Agents; Antioxidants; Cisplatin; Dioxoles; Drug Evaluation, Preclinical; Kidney; Kidney Diseases; Lignans; Male; Phytotherapy; Plant Extracts; Rats, Wistar; Sesamum

Acute stress induces tissue damage through excessive cellular apoptosis. In our study, the effects of sesamin on apoptosis and wound healing were investigated. The angiogenesis effect of sesamin was evaluated by the abilities of adherence, migration and tube formation in human umbilical vein endothelial cells (HUVECs). Our data demonstrated that treatment with sesamin dose-dependently promoted the proliferation, adherence, migration and enhanced their angiogenic ability

Topics: Angiogenesis Inducing Agents; Animals; Apoptosis; Cell Adhesion; Cell Movement; Cell Proliferation; Cell Survival; Dioxoles; Human Umbilical Vein Endothelial Cells; Humans; Lignans; Neovascularization, Physiologic; Rats; Rats, Sprague-Dawley; Signal Transduction; tert-Butylhydroperoxide; Wound Healing

As one of the major global health issues, allergic disease represents a considerable burden both on individual patients and public health. (-)-Asarinin (Asa), a lignan isolated from the roots of Asiasari radix, was reported to be associated with anti-allergic effect, but its efficacy and mechanism of action remain unclear. This study investigated the inhibitory effect of Asa on allergic reaction and its mechanism of action. Asa significantly suppressed Ag-sensitized human mast cell line LAD2 calcium mobilization, degranulation, and secretion. It also could reduce OVA-induced local and system anaphylaxis of mice in vivo. Further experiments revealed that Asa inhibit the mast cell activation by preventing the phosphorylation of Src family kinases. Moreover, after the IgE-dependent murine model of allergic rhinitis was treated with Asa, not only the concentration of histamine, total IgE, and IL-4 decreased, but also the inflammatory infiltrates and nasal mucosa incrassation were attenuated significantly. Meanwhile, Asa also inhibited the activation of mast cells induced by Compound48/80 in vivo and in vitro. In conclusion, Asa may serve as a potential novel Src family kinase inhibitor to inhibit IgE-dependent andIgE-independent allergic reaction and treat anaphylactic disease.

Topics: Animals; Dioxoles; Humans; Lignans; Mast Cells; Mice; src-Family Kinases

Eleutherococcus senticosus or Siberian ginseng is a medicinal plant containing adaptogenic substances believed to regulate immune responses. Both, the root and stem bark are commonly used in traditional medicines.. The purpose of the present study is to chemically characterize E. senticosus root and bark extracts and to compare their effects on functions of human primary macrophages.. HPLC-DAD-MS analysis was used to characterize chemical constituents of alcoholic extracts from E. senticosus root and bark. The data obtained and available databases were combined for network pharmacology analysis. Involvement of predicted pathways was further functionally confirmed by using monocyte-derived human macrophages and endotoxin-free E. senticosus root and bark extracts.. Chemical analysis showed that the root extract contained more syringin, caffeic acid, and isofraxidin than the bark extract. At variance, bark extract contained more sesamin and oleanolic acid. Coniferyl aldehyde and afzelin were below the limit of quantification in both extracts. Network pharmacology analysis indicated that constituents of E. senticosus might affect the immune cell phenotype and signaling pathways involved in cell metabolism and cytoskeleton regulation. Indeed, both extracts promoted actin polymerization, migration, and phagocytosis of E. coli by macrophages pointing to macrophage polarization towards the M2 phenotype. In addition, treatment with E. senticosus root and bark extracts decreased phosphorylation of Akt on Ser473 and significantly reduced expression of the hemoglobin scavenger receptor CD163 by macrophages. Neither extract affected expression of CD11b, CD80, or CD64 by macrophages. In addition, macrophages treated with the bark extract, but not with the root extract, exhibited activated p38 MAPK and NF-κB and released increased, but still moderate, amounts of proinflammatory TNF-α and IL-6, anti-inflammatory IL-10, and chemotactic CCL1, which all together point to a M2b-like macrophage polarization. Differently, the root extract increased the IL-4-induced expression of anti-inflammatory CD200R. These changes in monocytes are in agreement with an increased M2a macrophage polarization.. The ability of E. senticosus root and bark extracts to promote polarization of human macrophages towards anti-inflammatory M2a and M2b phenotypes, respectively, might underlay the immunoregulatory activities and point to potential wound healing promoting effects of this medicinal plant.

Topics: Anti-Inflammatory Agents; Cell Polarity; Coumarins; Dioxoles; Eleutherococcus; Glucosides; Humans; Lignans; Macrophages; NF-kappa B; Phenylpropionates; Plant Bark; Plant Extracts; Plant Roots; Plants, Medicinal

Sesamin, the most abundant lignan in sesame seed oil, has many biological activities. However, the underlying molecular mechanisms behind the regulatory effects of sesamin on endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) generation in endothelial cells (ECs) remain unclear. Sesamin induced the intracellular level of NO and eNOS phosphorylation in ECs in a concentration- and time-dependent manner. Additionally, sesamin induced levels of intracellular calcium, leading to the phosphorylation of calmodulin-dependent protein kinase II (CaMKII) at Thr286, calcium/calmodulin-dependent protein kinase kinase beta (CaMKKβ) at Ser511, protein kinase A (PKA) at Thr197, Akt at Ser473, and AMP-activated protein kinase (AMPK) at Thr172. In particular, blocking of the transient receptor potential vanilloid type 1 (TRPV1) channel by capsazepine (TRPV1 antagonist), as well as TRPV1 knockdown via TRPV1 silencing RNA, abrogated sesamin-induced PKA, Akt, AMPK, CaMKII, CaMKKβ, and eNOS phosphorylation and NO level in ECs. Furthermore, sesamin inhibited TNF-α-induced NF-κB translocation, intercellular adhesion molecule-1 expression, and monocyte adhesion. Sesamin triggered eNOS activity and NO production via activation of TRPV1-calcium signaling, which involved the phosphorylation of PKA, CaMKII, CaMKKβ, Akt, and AMPK. Sesamin may be useful for treating or preventing the endothelial dysfunction correlated with cardiovascular diseases.

Topics: AMP-Activated Protein Kinases; Dioxoles; Endothelial Cells; Lignans; Nitric Oxide; Nitric Oxide Synthase Type III; Phosphorylation; Proto-Oncogene Proteins c-akt

BACKGROUND Osteoporosis is a metabolic osteopathy characterized by abnormal bone mass and microstructure that has become a public health problem worldwide. Cuscutae semen (CS) is a traditional Chinese medicine (TCM) that has a positive effect on the prevention and treatment of osteoporosis. However, the mechanism of CS is unclear. Therefore, this study aimed to reveal the possible molecular mechanism involved in the effects of CS on osteoporosis based on a network pharmacology approach. MATERIAL AND METHODS The inactive and active ingredients of CS were identified by searching the pharmacology analysis platform of the Chinese medicine system (TCMSP), and the targets of osteoporosis were screened in the relevant databases, such as GeneCards, PubMed, and the Comparative Toxicogenomics Database (CTD). The network of "medicine-ingredients-disease-targets (M-I-D-T)" was established by means of network pharmacology, and the key targets and core pathways were determined by R analysis. Molecular docking methods were used to evaluate the binding activity between the target and the active ingredients of CS. RESULTS Eleven active ingredients were identified in CS, and 175 potential targets of the active ingredients were also identified from the TCMSP. Moreover, we revealed 22 539 targets related to osteoporosis in the 3 well-established databases, and we determined the intersection of the disease targets and the potential targets of the active ingredients; 107 common targets were identified and used in further analysis. Additionally, biological processes and signaling pathways involved in target action, such as fluid shear stress, atherosclerosis, cancer pathways, and the TNF signaling pathway, were determined. Finally, we chose the top 5 common targets, CCND1, EGFR, IL6, MAPK8, and VEGFA, for molecular docking with the 11 active ingredients of CS. CONCLUSIONS This study suggested that CS has multiple ingredients and multiple targets relevant to the treatment of osteoporosis. We determined that the active ingredient, sesamin, may be the most crucial ingredient of CS for the treatment of osteoporosis. Additionally, the network pharmacology method provided a novel research approach to analyze the function of complex ingredients.

Topics: Catalytic Domain; Cyclins; Dioxoles; Drugs, Chinese Herbal; ErbB Receptors; Gene Ontology; Humans; Interleukin-6; Lignans; Mitogen-Activated Protein Kinase 8; Molecular Docking Simulation; Molecular Targeted Therapy; Osteoporosis; Protein Interaction Maps; Thermodynamics; Vascular Endothelial Growth Factor A

The effects of roasting and in vitro digestion on total phenolic content (TPC), total flavonoid content (TFC), phenolic profiles, and antioxidant activity of water-soluble extracts from six varieties of sesame were investigated in this study. Our results showed that the major phenolic compounds in raw, roasted and digested sesame were gallic acid (GA), protocatechuic acid (PA), 4-hydroxybenzoic acid (4 HBA), ferulic acid (FA) and quercetin (Quer). Roasting significantly increased the TPC, pinoresinol diglucoside (PD), sesamol, as well as the content of phenolic compounds (especially GA, PA, 4 HBA and Quer) in sesame, but kept or reduced the TFC, sesamin and sesamolin. After roasting, the antioxidant potency composite index (ACI) of six varieties of sesame was significantly increased by 29.8%-216.6%. Additionally, the ACI of gastric digestion was significantly higher than that of oral and intestinal digestion during the in vitro digestion of the roasted-sesame, except for the varieties of Ganzhi 9 and Ganzhi 17. This study showed that five phenolic compounds (GA, PA, 4 HBA, p-coumaric acid, Quer) and sesamol of the water-soluble extracts contributed to the antioxidant activities of the digestive products of sesame.

Topics: Anticarcinogenic Agents; Antioxidants; Benzodioxoles; Coumaric Acids; Digestion; Dioxoles; Flavonoids; Gallic Acid; Hydroxybenzoates; Lignans; Parabens; Phenol; Phenols; Plant Extracts; Principal Component Analysis; Propionates; Quercetin; Seeds; Sesamum

Changing consumption patterns and increasing health awareness, especially in Europe, are resulting in an increased demand for sesame seeds. In 2016, Asia imported the highest quantity of sesame seeds, followed by Europe and North America. We examined, for the first time, the effects of treatment with sesame oil and sesamin in hearing impairment models. Sesame oil exhibited an ameliorative effect on auditory impairment in a hair cell line in zebrafish and mice. In ototoxic zebrafish larvae, neuromasts and otic cells increased in numbers because of sesame oil. Furthermore, auditory function in noise-induced hearing loss (NIHL) was studied through auditory brainstem response to evaluate the therapeutic effects of sesame oil. Sesame oil reduced the hearing threshold shift in response to clicks and 8, 16-kHz tone bursts in NIHL mice. Auditory-protective effect of sesame oil was seen in zebrafish and mice; therefore, we used chromatographic analysis to study sesamin, which is the major effective factor in sesame oil. To investigate its effects related to auditory function, we studied the hearing-related gene,

Topics: Animals; Cell Line; Dioxoles; Gene Expression; Hair Cells, Auditory; Hearing Loss, Noise-Induced; Larva; Lignans; Mice; Sesame Oil; Zebrafish

Sesamin is a major lignan in sesame seeds, and a recent meta-analysis of controlled trials indicated that sesamin intake decreases blood pressure. The antihypertensive effect of sesamin has been suggested to be due to sesamin-mediated suppression of 20-hydroxyeicosatetraenoic acid production catalyzed by CYP4F2. However, the detailed mechanism underlying inhibition of CYP4F2 function by sesamin remains unclear. In this study, the effects of sesamin on catalytic activity of CYP4F2 were investigated in vitro. Sesamin inhibited luciferin-4F2/3 O-dealkylase activity of recombinant human CYP4F2 with an IC

Topics: Animals; Baculoviridae; Cytochrome P450 Family 4; Dioxoles; Insecta; Lignans; Microsomes; NADP; Recombinant Proteins

Sesamin and sesamolin are two typical and important lignans isolated from sesame oil. Various studies have shown the bioactivity, physiological activity, and potential health benefits of the two components. In this study, a rapid method for the simultaneous determination of sesamin and sesamolin in sesame oils was proposed. The excitation-emission fluorescence spectra of the oils were obtained after a simple pretreatment, then self-weighted alternating trilinear decomposition was used to extract the quantitative information from the very overlapping spectra.. It was found that reasonable quantification results could be obtained with the limits of detection for the two lignans. These limits were 0.05 mg/g and 0.24 mg/g, and the limits of quantitation were 0.14 mg/g and 0.74 mg/g, respectively. The average recoveries for sesamin and sesamolin were 99.05% and 94.97%.. The results indicate that, with simple sample pretreatment, the application for combining excitation-emission fluorescence spectra and self-weighted alternating trilinear decomposition can be a useful and sensitive tool for the determination of lignans in sesame oil. © 2020 Society of Chemical Industry.

Topics: Dioxoles; Fluorescence; Lignans; Sesame Oil; Sesamum; Spectrometry, Fluorescence

The conversion of sesame lignans is of interest because the derived products may have potential applications. Here, in investigating the transformation of sesamin and sesamolin, main endogenous sesame lignans in sesame seeds, in both acidic aqueous and anhydrous systems, 7

Topics: Acids; Catalysis; Dioxoles; Hydrogen Peroxide; Lignans; Molecular Structure; Seeds; Sesamum; Stereoisomerism

Sesamin-treated human oral cancer cell lines FaDu, HSC-3, and Ca9-22 were subjected to a wound-healing assay. Furthermore, Western blotting was performed to assess the effect of sesamin on the expression levels of matrix metalloproteinase (MMP)-2 and proteins of the MAPK signaling pathway, including p-ERK1/2, P-p38, and p-JNK1/2. In addition, we investigated the association between MMP-2 expression and the MAPK pathway in sesamin-treated oral cancer cells. Sesamin inhibited cell migration and invasion in FaDu, Ca9-22, and HSC-3 cells and suppressed MMP-2 at noncytotoxic concentrations (0 to 40 μM). Furthermore, sesamin significantly reduced p38 MAPK and JNK phosphorylation in a dose-dependent manner in FaDu and HSC-3 cells.. These results indicate that sesamin suppresses the migration and invasion of HNSCC cells by regulating MMP-2 and is thus a potential antimetastatic agent for treating HNSCC.

Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Movement; Cell Survival; Dioxoles; Head and Neck Neoplasms; Humans; Lignans; MAP Kinase Kinase 4; MAP Kinase Signaling System; Matrix Metalloproteinase 2; Neoplasm Metastasis; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Squamous Cell Carcinoma of Head and Neck; Zanthoxylum

Sesamin is a functional ingredient in sesame (Sesamum indicum) seeds and has many physiological effects. This study investigated whether sesame lignans, sesamin and episesamin (1:1), can suppress age-related disorders of the kidney.. Twenty-month-old mice were divided into three groups, and each group received a regular diet (O-C), diet containing sesame lignans (O-SE), and diet containing sesame lignans and α-tocopherol (VE; O-SE+VE), respectively, for 5 months. Six-month-old young mice (Y-C) were compared to the older mice.. Renal lipofuscin deposition was increased in the O-C group compared to that in the Y-C group and its deposition with aging was significantly decreased in both O-SE and O-SE+VE groups. Plasma blood urea nitrogen levels in the O-C group increased compared to those in the Y-C group; however, those in both O-SE and O-SE+VE groups did not differ from those in the Y-C group. The number of podocytes in the O-C group decreased compared to that in the Y-C group and this effect was attenuated in the O-SE and O-SE+VE groups. The effect was strongest in the O-SE+VE group. Histological examinations showed that glomerular hypertrophy accompanied by mesangial hyperplasia and renal tubular degeneration was less severe in the O-SE and O-SE+VE groups than in the O-C group. Moreover, age-related increases in the mRNA expression of NADPH oxidase- and inflammation-related genes, including p67phox, p40phox, TNFα, and IL-6, in the kidney were suppressed in the O-SE and O-SE+VE groups.. Sesame lignans might be useful to suppress age-related kidney disorders, and these effects could be enhanced with VE.

Topics: Aging; alpha-Tocopherol; Animals; Antioxidants; Diet; Dioxoles; Kidney Diseases; Lignans; Male; Mice; Mice, Inbred C57BL; Sesamum

Transient receptor potential melastatin 8 (TRPM8) is a calcium ion-permeable cation channel that is used as a prognostic marker and therapeutic target for different tumor types. To identify natural selective TRPM8 antagonists, we tested 158 traditional Chinese medicine (TCM) compounds for the ability to inhibit TRPM8. Calcium mobilization assays were used to evaluate the 158 TCM compound components in HEK293 cells stably expressing TRPM8. An identified putative TRPM8 antagonist, sesamin, was further evaluated. Publicly available cancer OMICS data were used to explore the expression of TRPM8, its gene regulatory network, and the survival of patients with prostate adenocarcinoma (PRAD). The cytotoxicity and specificity of sesamin to TRPM8 were tested in HEK293/TRPM8 cells. The effect of sesamin on cell proliferation in PRAD cell lines was assessed. Sesamin selectively inhibited TRPM8 in HEK293/TRPM8 cells (IC50: 9.78 μM), and a molecular docking study confirmed the binding of sesamin to TRPM8. TRPM8 was highly overexpressed in PRAD, and high TRPM8 expression was associated with poor survival of PRAD patients. Functional network analysis suggested that TRPM8 has key effects on proliferation, survival, and invasion of prostate cancer cells. Cell proliferation assays supported these findings and showed that sesamin inhibited the proliferation of PRAD cell lines DU145 and LNCaP cells. These data revealed that abnormal TRPM8 expression is associated with PRAD and that sesamin is a new anti-PRAD candidate drug, exerting inhibitory effects on TRPM8.

Topics: Adenocarcinoma; Cell Line, Tumor; Cell Proliferation; Dioxoles; HEK293 Cells; Humans; Lignans; Male; Molecular Docking Simulation; Molecular Structure; Prostatic Neoplasms; TRPM Cation Channels

Although cold-pressed sesame oil (CPSO) possesses high nutritional value, its application in the food industry is limited due to its poor oxidative stability. The aim of this study was to enhance the oxidative stability of CPSO by complex coacervation microcapsule technology with gelatin and gum Arabic as wall materials. The characterization of CPSO microcapsules were evaluated by a particle image analyzer, a laser particle size distribution analyzer, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA). The encapsulation efficiency (EE) reached 90.25%. The average particle size of the microcapsules was approximately 117.1 μm and many oil droplets were encapsulated by complex coacervation to form a multinuclear spherical microcapsule. The FTIR study confirmed that the process of complex coacervation was formed between gelatin and gum Arabic by electrostatic interactions. The TGA study suggested that the microcapsules had good heat resistance. The fatty acid composition, the content of sesamin, sesamolin and vitamin E in CPSO were determined before and after microencapsulation. It showed that the microencapsulation process had almost no effect on the fatty acid composition, sesamin and sesamolin, only Vitamin E was slightly lost during the microencapsulation process. The accelerated storage test showed that microencapsulation significantly increased the oxidative stability of CPSO.

Topics: Capsules; Chemical Phenomena; Dioxoles; Drug Compounding; Fatty Acids; Food Storage; Food Technology; Gelatin; Gum Arabic; Lignans; Molecular Imaging; Oxidation-Reduction; Particle Size; Sesame Oil; Static Electricity; Vitamin E

A recent report demonstrated that sesamin strongly and non-competitively inhibits S-warfarin 7-hydroxylation activity in human liver microsomes with a K

Topics: Cytochrome P-450 CYP2C9; Dioxoles; Enzyme Inhibitors; Humans; Hydroxylation; Kinetics; Lignans; Microsomes, Liver; Molecular Structure; Warfarin

Sesamin (SSM) and sesamolin (SesA) are the two major furofuran lignans of sesame oil and they have been previously noticed to exert various biological actions. However, their modulatory actions on different types of ionic currents in electrically excitable cells remain largely unresolved. The present experiments were undertaken to explore the possible perturbations of SSM and SesA on different types of ionic currents, e.g., voltage-gated Na

Topics: Adenoma; Animals; Antioxidants; Dioxoles; Ion Channel Gating; Lignans; Pituitary Neoplasms; Potassium Channels, Voltage-Gated; Rats; Sesame Oil; Tumor Cells, Cultured; Voltage-Gated Sodium Channels

Programmed death ligand 1 (PD-L1) is overexpressed in some metastatic breast cancer subtypes, specifically triple-negative breast cancer (TNBC). This feature can assist in the eradication of anti-tumor immunity, thereby enhancing the survival of the tumor. This study aims to explore how sesamin affects PD-L1 expression in breast cancer cells and its related molecular mechanisms. We found high levels of expression of PD-L1 in both mRNA and protein levels in the TNBC cell line, MDA-MB231, but not in the luminal type-breast cancer cell line, MCF-7. We then demonstrated the tumor suppressive effect of sesamin, which induced the inhibition of cell proliferation in MDA-MB231 cells. Additionally, sesamin triggered PD-L1 downregulation (both mRNA and protein) through the inhibition of AKT, NF-κB and JAK/Stat signaling in MDA-MB231 cells. Moreover, the migration ability of MDA-MB231 cells was effectively diminished by sesamin via inhibition of the activation of MMP-9 and MMP-2. In summary, this study demonstrated that sesamin suppresses MDA-MB231 breast cancer cells' proliferation and migration; and decreases the expression of PD-L1 via the downregulation of AKT, NF-κB, and JAK/Stat signaling. Therefore, sesamin may be an effective alternative and novel therapeutic option for immunotherapy in breast cancer cells with high PD-L1 expression.

Topics: Adenocarcinoma; B7-H1 Antigen; Biomarkers, Tumor; Breast Neoplasms; Cell Proliferation; Dioxoles; Female; Humans; Janus Kinases; Lignans; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; MCF-7 Cells; NF-kappa B; Proto-Oncogene Proteins c-akt; Signal Transduction; STAT Transcription Factors; Triple Negative Breast Neoplasms; Up-Regulation

Sesamin is the main lignan in sesame and is reported to have many benefits and medicinal properties. However, its protective effects against fluoride-induced damage in the liver of zebrafish have not been elucidated. Our previous studies found that fluoride exposure caused damage to the liver of zebrafish. In the study, the effects of sesamin on oxidative stress and immune damage in liver of zebrafish exposed to fluoride were measured. The results indicated that fluoride exposure damaged the microstructures of liver, increased significantly the oxidative stress, decreased remarkably the activities of ACP, AKP, and LZM, and affected obviously the expressions of immune-related genes. Treatment with sesamin remarkably attenuated fluoride-induced liver damage in a dose-dependent manner, indicated by the histopathological observation. Furthermore, sesamin treatment also significantly inhibited the production of ROS and oxidative stress, such as the decrease of lipid peroxidation level and the increase of CAT and SOD activities in liver. Sesamin treatment reversed the activities of immune-related enzymes and the expressions of immune-related genes in liver exposed to fluoride. These findings suggested that sesamin could protect the liver from fluoride-induced immune damage by oxidative stress downstream-mediated changes in reversing the activities of immune-related enzymes and the expressions of immune-related genes. Taken together, sesamin plays an important role in maintaining hepatic health and preventing liver from toxic damage caused by fluoride.

Topics: Animals; Chemical and Drug Induced Liver Injury; Cytokines; Dioxoles; Fluorides; Gene Expression Regulation; Lignans; Liver; Male; Oxidative Stress; Protective Agents; Water Pollutants, Chemical; Zebrafish

The widespread problem of a 2019-novel coronavirus (SARS-CoV-2) strain outbreak in Wuhan, China has prompted a search for new drugs to protect against and treat this disease. It is necessary to immediately investigate this due to the mutation of the viral genome and there being no current protective vaccines or therapeutic drugs. Molecular modelling and molecular docking based on in silico screening strategies were employed to determine the potential activities of seven HIV protease (HIV-PR) inhibitors, two flu drugs, and eight natural compounds. The computational approach was carried out to discover the structural modes with a high binding affinity for these drugs on the homology structure of the Wuhan coronavirus protease (SARS-CoV-2 PR). From the theoretical calculations, all the drugs and natural compounds demonstrated various favorable binding affinities. An interesting finding was that the natural compounds tested had a higher potential binding activity with the pocket sites of SARS-CoV-2 PR compared to the groups of HIV-PR inhibitors. The binding modes of each complex illustrated between the drugs and compounds interacted with the functional group of amino acids in the binding pocket via hydrophilic, hydrophobic, and hydrogen bond interactions using the molecular dynamics simulation technique. This result supports the idea that existing protease inhibitors and natural compounds could be used to treat the new coronavirus. This report sought to provide fundamental knowledge as preliminary experimental data to propose an existing nutraceutical material against viral infection. Collectively, it is suggested that molecular modelling and molecular docking are suitable tools to search and screen for new drugs and natural compounds that can be used as future treatments for viral diseases.

Topics: Antiviral Agents; Binding Sites; Coronavirus 3C Proteases; Cysteine Endopeptidases; Dietary Supplements; Dioxoles; Diterpenes; Hydrogen Bonding; Lignans; Molecular Docking Simulation; Molecular Dynamics Simulation; Molecular Structure; Protease Inhibitors; Protein Conformation; Viral Nonstructural Proteins

Previously, we have investigated the therapeutic mechanism of Qingzao Jiufei Decoction (QZJFD), a Chinese classic prescription, on acute lung injury (ALI), however, which remained to be further clarified together with the underlying efficacy related compounds for quality markers (Q-markers).. To explore Q-markers of QZJFD on ALI by integrating a stepwise multi-system with 'network pharmacology-metabolomics- pharmacokinetic (PK)/ pharmacodynamic (PD) modeling'.. First, based on in vitro and in vivo component analysis, a network pharmacology strategy was developed to identify active components and potential action mechanism of QZJFD on ALI. Next, studies of poly-pharmacology and non-targeted metabolomics were used to elaborate efficacy and verify network pharmacology results. Then, a comparative PK study on active components in network pharmacology was developed to profile their dynamic laws in vivo under ALI, suggesting Q-marker candidates. Next, quantified analytes with marked PK variations after modeling were fitted with characteristic endogenous metabolites along drug concentration-efficacy-time curve in a PK-PD modeling to verify and select primary effective compounds. Finally, Q-markers were further chosen based on representativeness among analytes through validity analysis of PK quantitation of primary effective compounds.. In virtue of 121 and 33 compounds identified in vitro and in vivo, respectively, 33 absorbed prototype compounds were selected to construct a ternary network of '20 components-47 targets-113 pathways' related to anti-ALI of QZJFD. Predicted mechanism (leukocytes infiltration, cytokines, endogenous metabolism) were successively verified by poly-pharmacology and metabolomics. Next, 18 measurable components were retained from 20 analytes by PK comparison under ALI. Then, 15 primary effective compounds from 18 PK markers were further selected by PK-PD analysis. Finally, 9 representative Q-markers from 15 primary effective compounds attributed to principal (chlorogenic acid), ministerial (methylophiopogonanone A, methylophiopogonanone B), adjuvant (sesamin, ursolic acid, amygdalin), conductant drugs (liquiritin apioside, liquiritigenin and isoliquiritin) in QZJFD, were recognized by substitutability and relevance of plasmatic concentration at various time points.. 9 Q-markers for QZJFD on ALI were identified by a stepwise integration strategy, moreover, which was a powerful tool for screening Q-makers involved with the therapeutic action of traditional Chinese medicine (TCM) prescription and promoting the process of TCM modernization and scientification.

Topics: Acute Lung Injury; Administration, Oral; Amygdalin; Animals; Biological Availability; Biomarkers, Pharmacological; Chalcone; Chlorogenic Acid; Dioxoles; Drugs, Chinese Herbal; Flavanones; Glucosides; Lignans; Male; Metabolomics; Rats, Wistar; Triterpenes; Ursolic Acid

Sepsis is currently one of the leading causes of death in intensive care units (ICUs). Sesamin was previously reported to inhibit inflammation. However, no studies have revealed the impact of sesamin on sepsis.. We studied the mechanism underlying the effect of sesamin on the pathophysiology of sepsis through the HMGB1/TLR4/IL-33 signalling pathway.. We found mice in the sepsis group survived for only 4 days, while those treated with sesamin survived for 6-7 days. In addition, sesamin significantly relieved the increase in the levels of MPO (21%, 33.3%), MDA (40.5% and 31.6%), DAO (1.24-fold and 2.31-fold), and pro-inflammatory cytokines such as TNF-α (75% and 79%) and IL-6 (1-fold and 1.67-fold) 24 and 48 h after sepsis induction and downregulated the expression of HMGB1, TLR4, and IL-33 while upregulating the expression of ZO-1 and occludin.. Sesamin improved the 7-day survival rate of septic mice, suppressed the inflammatory response in sepsis through the HMGB-1/TLR4/IL-33 signalling pathway, and further alleviated intestinal injury.

Topics: Animals; Bacteria; Cell Line; Cytokines; Dioxoles; Disease Models, Animal; Epithelial Cells; HMGB1 Protein; Humans; Inflammation; Interleukin-33; Intestinal Mucosa; Lignans; Male; Mice; Mice, Inbred BALB C; Occludin; Sepsis; Signal Transduction; Toll-Like Receptor 4; Zonula Occludens-1 Protein

Sesamum spp. (sesame) are known to accumulate a variety of lignans in a lineage-specific manner. In cultivated sesame (Sesamum indicum), (+)-sesamin, (+)-sesamolin and (+)-sesaminol triglucoside are the three major lignans found richly in the seeds. A recent study demonstrated that SiCYP92B14 is a pivotal enzyme that allocates the substrate (+)-sesamin to two products, (+)-sesamolin and (+)-sesaminol, through multiple reaction schemes including oxidative rearrangement of α-oxy-substituted aryl groups (ORA). In contrast, it remains unclear whether (+)-sesamin in wild sesame undergoes oxidation reactions as in S. indicum and how, if at all, the ratio of the co-products is tailored at the molecular level. Here, we functionally characterised SrCYP92B14 as a SiCYP92B14 orthologue from a wild sesame, Sesamum radiatum, in which we revealed accumulation of the (+)-sesaminol derivatives (+)-sesangolin and its novel structural isomer (+)-7´-episesantalin. Intriguingly, SrCYP92B14 predominantly produced (+)-sesaminol either through ORA or direct oxidation on the aromatic ring, while a relatively low but detectable level of (+)-sesamolin was produced. Amino acid substitution analysis suggested that residues in the putative distal helix and the neighbouring heme propionate of CYP92B14 affect the ratios of its co-products. These data collectively show that the bimodal oxidation mechanism of (+)-sesamin might be widespread across Sesamum spp., and that CYP92B14 is likely to be a key enzyme in shaping the ratio of (+)-sesaminol- and (+)-sesamolin-derived lignans from the biochemical and evolutionary perspectives.

Topics: Amino Acid Sequence; Biosynthetic Pathways; Cytochrome P-450 Enzyme System; Dioxoles; Furans; Glucosides; Lignans; Models, Molecular; Oxidation-Reduction; Phylogeny; Plant Proteins; Seeds; Sequence Alignment; Sesamum

Sesamin is a major component in lignans of sesame seeds, has been described to possess a lot of biological activity. The main objective of our study was to investigate the inhibitory effect and novel molecular mechanisms of sesamin on carrageenan-induced lung inflammation in rats. Here we showed that sesamin can obviously reduce polymorphonuclear neutrophils infiltration and exudate volume. Further studies exhibited sesamin can inhibit cytokines release, polymorphonuclear neutrophils markers production and the degree of lung tissues injury. Western blot analysis revealed that sesamin can inhibit the TRAF6 expression and NF-κB pathway activation in lung tissue. We found that sesamin can increase the expression of A20 and TAX1BP1 in lung tissues, and the interaction between the two molecules. In conclusion, all these results demonstrated that sesamin can attenuate carrageenan-induced lung inflammation, the mechanisms that may be related to upregulation of the novel target A20 and TAX1BP1 which can negative regulation for NF-κB pathway. Importantly, this is the first evidence showing that TAX1BP1 can be as a novel regulatory target to attenuate the lung inflammation.

Topics: Animals; Antioxidants; Apoptosis Regulatory Proteins; Biomarkers; Carrageenan; Dioxoles; Gene Expression Regulation; Inflammation; Lignans; Lung Diseases; Neoplasm Proteins; Neutrophils; NF-kappa B; Pleural Effusion; Rats; Tumor Necrosis Factor alpha-Induced Protein 3; Up-Regulation

Gomisin A (Gom A), a lignan isolated from

Topics: Animals; Cell Line; Cyclooctanes; Dioxoles; Ion Transport; Kinetics; Lignans; Potassium Channels, Voltage-Gated; Rats; Schisandra; Voltage-Gated Sodium Channel Blockers; Voltage-Gated Sodium Channels

In this work, the aim of our study was to assess whether sesamin could influence the pharmacokinetics of ivabradine and its active metabolite N-desmethylivabradine in rats. At the begining, 12 healthy male Sprague-Dawley rats were randomly divided into two groups: The rats were received an oral administration of 1.0mg/kg ivabradine alone (the control group), and the rats were given 1.0mg/kg ivabradine co-administered with 50mg/kg sesamin by gavage (the test group). After that, blood samples were collected from the tail vein of rats, and ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) were used for determing the plasma concentrations of ivabradine and N-desmethylivabradine in rats. Finally, the pharmacokinetic parameters were estimated using DAS 2.0 software. As the results, the pharmacokinetic parameters (t

Topics: Administration, Oral; Animals; Area Under Curve; Cardiovascular Agents; Chromatography, High Pressure Liquid; Dioxoles; Ivabradine; Lignans; Male; Rats, Sprague-Dawley; Tandem Mass Spectrometry

The composition and the relative variation of secondary metabolites of

Topics: Chemical Fractionation; Chloroform; Chromatography, High Pressure Liquid; Color; Dioxoles; Gas Chromatography-Mass Spectrometry; Lamiales; Lignans; Lignin; Plant Extracts; Temperature; Wood

Enantiomers have generally been reported mostly for racemic mixtures with a 1:1 ratio, as in that case there were weak Cotton effects in the ECD spectrum and negligible optical rotations. A furofuran lignan (sesamin), with a remarkable rotation and significant Cotton effects, was isolated from

Topics: Amyloid beta-Peptides; Dioxoles; Furans; Juglans; Lignans; Molecular Docking Simulation; Molecular Dynamics Simulation; Molecular Structure; Optical Rotation; Peptide Fragments; Stereoisomerism

Topics: Animals; Antioxidants; Caco-2 Cells; Colitis; Dioxoles; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases; HEK293 Cells; Humans; Lignans; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2; Oxidative Stress; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Transcriptional Activation

Ultraviolet (UV) exposure has been demonstrated as the most critical factor causing extrinsic skin aging and inflammation. This study explored the protective effects and mechanisms of sesamin against skin photodamage. Sesamin reduced intracellular reactive oxygen species production after UVB irradiation in human dermal fibroblasts. The sesamin treatment attenuated mitogen-activated protein (MAP) kinase phosphorylation and matrix metalloproteinase (MMPs) overexpression induced by UVB exposure, and it significantly enhanced the tissue inhibitor of metalloproteinase-1 protein expression. Sesamin also elevated the total collagen content in human fibroblasts by inhibiting UVB-induced mothers against decapentaplegic homolog 7 (Smad7) protein expression. Sesamin reduced UVB-induced inducible nitric oxide synthase (i-NOS) and cyclooxygenase-2 (COX-2) overexpression and inhibited nuclear factor-kappa B (NF-κB) translocation. Moreover, sesamin may regulate the c-Jun N-terminal kinases (JNK) and p38 MAP kinase pathways, which inhibit COX-2 expression. Sesamin could reduce UVB-induced inflammation, epidermal hyperplasia, collagen degradation, and wrinkle formation in hairless mice. It also reduced MMP-1, interleukin (IL-1), i-NOS, and NF-κB in the mouse skin. These results demonstrate that sesamin had antiphotodamage and anti-inflammatory activities. Sesamin has potential for use as a skin protection agent in antiphotodamage and skin care products.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Line; Dermatitis; Dioxoles; Disease Models, Animal; Fibroblasts; Gene Expression Regulation; Humans; Hyperplasia; Lignans; Matrix Metalloproteinases; Mice; Mice, Hairless; Mitogen-Activated Protein Kinases; Phosphorylation; Reactive Oxygen Species; Skin; Skin Aging; Tissue Inhibitor of Metalloproteinase-1; Ultraviolet Rays

A combination method of ultra-performance liquid chromatography (UPLC) coupled with diode array detection has been developed for quality evaluation of Qinma prescription (QMP), based on chromatographic fingerprint technology with the similarity analysis (SA) and the quantitative analysis of 12 components by hierarchical cluster analysis (HCA). The established method has been validated by linearity, precision, repeatability, stability and recovery tests. The UPLC fingerprints with 17 common peaks of 5 QMP samples prepared by different extraction methods including water decoction extraction, water extraction-ethanol precipitation method, ethanol reflux extraction, ethanol extraction-water precipitation method and methanol ultrasonic extraction were obtained, and the SA results indicated that similarity index was greatly influenced by the large peak. The similarity index ranged from 0.816 to 0.999 basing on 17 peaks, which has been decreased to 0.683-0.999 basing on 16 peaks without the large peak of baicalin (BA). The results of simultaneous quantification of 12 components in these 5 QMP samples proved that BA, gallic acid (GA), wogonoside (WOG) and gentiopicroside (GEN) were the major ingredients in QMP with high contents >1.44 (mg/g), indicating that ethanol reflux was the most effective extraction method. Integrating fingerprint analysis, simultaneous determination and HCA, the established method is rapid, sensitive, accurate and readily applicable. All the results indicated that the combination method can control the quality of QMP and its related traditional Chinese medicinal compounds more comprehensively and scientifically.

Topics: Catechols; Chemical Fractionation; Chromatography, High Pressure Liquid; Dioxoles; Drugs, Chinese Herbal; Fatty Alcohols; Flavonoids; Gallic Acid; Lignans; Limit of Detection; Linear Models; Reproducibility of Results

Sesamin, a lignan from sesame seed, has been reported to attenuate chronic mild stress-induced depressive-like behaviors. Gut microbiota play pivotal roles in mediating psychological behaviors by regulating gut barrier integrity and systemic inflammatory responses. Here, we found that oral sesamin administration (50 mg/kg·bodyweight/day) significantly attenuated depressive, aversive, repetitive, and anxiety-like behaviors in a long-term multiple nonsocial stress-treated mice model. Sesamin inhibited stress-induced gut barrier integrity damage, reduced circulating lipopolysaccharide (LPS) levels, and suppressed neuroinflammatory responses. Moreover, sesamin treatment also restructured the gut microbiome by enhancing the relative abundances of Bacteroidales and S24-7. The correlation analysis indicated that the microbiota composition changes were strongly correlated with behavioral disorders, serotonin, norepinephrine, and LPS levels. In conclusion, sesamin has preventive effects on stress-induced behavioral and psychological disorders, which might be highly related to the reshaped microbiota composition. This study provides a clue for understanding the systemic mechanism of anti-depression effects of sesamin.

Topics: Animals; Bacteria; Behavior; Depression; Dietary Supplements; Dioxoles; Gastrointestinal Microbiome; Humans; Lignans; Male; Mice; Oxidative Stress; Plant Extracts; Seeds; Sesamum; Stress, Psychological

Sesamin (SES) has the ameliorating effect on L02 hepatocyte model of insulin resistance induced by high glucose and high insulin, based on insulin receptor signaling pathway IRS/PI3K/Akt. Treatment with SES (200, 100μg/ml) increased glucose consumption, glucose uptake and the intracellular glycogen synthesis of L02 hepatocyte model of insulin resistance significantly. Moreover, treatment with SES promoted the gene and protein expression levels of insulin receptor (InsR) and the post-receptor associated proteins, such as insulin receptor substrate 1 (IRS1), insulin receptor substrate 2 (IRS2), PI3K (phosphatidylinositol 3-kinase), GLUT4 (glucose transporter 4) significantly, which were determined by RT-PCR and immunoblot analysis. In conclusion, SES has the ameliorating effect on L02 hepatocyte model of insulin resistance induced by high glucose/high insulin, which might be related to its effect on promoting expression of insulin receptor and its associated proteins of IRS-PI3K-Akt passway, and thus promoting insulin sensitivity.

Topics: Antigens, CD; Cell Line; Chromatography, High Pressure Liquid; Dioxoles; Glucose; Glucose Transporter Type 4; Glycogen; Hepatocytes; Humans; Immunoblotting; Insulin Receptor Substrate Proteins; Insulin Resistance; Lignans; Receptor, Insulin; Reverse Transcriptase Polymerase Chain Reaction

By virtue of their regulatory role in the biological process, certain protein-protein complexes form potential targets for designing and discovery of drugs. Alteration set in the controlled formation of such complexes results in dysregulation of several metabolic processes, leading to diseased condition. β-catenin/Tcf4 complex is one such protein-protein complex found altered in colorectal epithelial cells resulting in activation of target genes leading to cancer. Recently, certain lignans from seeds of the oil crop sesame were found inhibiting initiation and progression of this type of cancer. Molecular mechanism involved in the process, however, is not yet known. By an in silico study, we present here a possible mechanism of interaction between the sesame lignans and β-catenin leading to inhibition of formation of the said complex, thereby elevating some of these ligands as potential lead molecules in the development of drugs for treatment of colon cancer. To achieve this objective, we performed docking, molecular dynamics simulation, and binding free energy analysis of target-ligand complexes. Using computational alanine scanning approach, the key pocket residues of β-catenin that interact with Tcf4 in the formation of complex were identified. The test molecules were initially evaluated for their drug-like properties by application of Lipinski's rule of five. Results of this study revealed that Sesamin, a furofuran lignan from sesame, has the highest affinity for β-catenin particularly with its residues that interact with Tcf4 and thus serving as a potential lead molecule for development of a drug for colon cancer.

Topics: beta Catenin; Binding Sites; Colonic Neoplasms; Computer Simulation; Dioxoles; Humans; Lignans; Models, Molecular; Molecular Docking Simulation; Protein Binding; Protein Conformation; Transcription Factor 4

Safe, affordable and efficacious agents are urgently required for cancer prevention. Sesamin, a lipid‑soluble lignan from sesame (Sesamum indicum) displays anticancer activities through an unknown mechanism. In the present study, the anticancer activity of sesamin via cyclooxygenase 2 (COX2) was investigated in lung cancer. Quantitative polymerase chain reaction was performed to determine the mRNA expression levels of COX2 in cells, while western blot analysis was used to determine its protein expression levels. Cell proliferation was evaluated by Cell Counting Kit‑8 assay, while apoptosis and cell cycle analyses were conducted by flow cytometry. The results indicated that COX2 expression was upregulated in lung cancer cell lines compared with human normal lung epithelial cell line BEAS‑2B and sesamin was demonstrated to decrease the levels of COX2, inhibit the proliferation of lung cancer cells and promote their apoptosis in a concentration‑dependent manner. Furthermore, decreased COX2 expression potentiated sesamin‑induced apoptosis and G1‑phase arrest, which was correlated with the suppression of gene products associated with cell apoptosis (Bcl‑2 and Bax) and the cell cycle (cyclin E1). In addition, cotreatment with the COX2 inhibitor CAY10404 and sesamin downregulated the expression of downstream molecules of COX2 [including interleukin (IL)1β, IL6 and tumor necrosis factor α] compared with CAY10404 or sesamin alone. Furthermore, cotreatment with sesamin and CAY10404 markedly reduced the levels of phosphorylated protein kinase B (pAkt) and phosoinositide 3 kinase (PI3K) in three lung cancer cell lines. PI3K expression was observed to be under the control of COX2, possibly forming a negative feedback loop. In addition, PI3K depletion induced apoptosis and G1‑phase arrest in A549 cells. These results suggested that sesamin blocked the pAkt‑PI3K signaling pathway by downregulating the expression of COX2, therefore resulting in cell cycle arrest and increased apoptosis in vitro. In conclusion, inhibition of COX2 increased the sensitivity of lung cancer cells to sesamin by modulating pAkt‑PI3K signaling. These results may aid the development of more selective agents to overcome cancer.

Topics: Apoptosis; Cell Cycle Checkpoints; Cell Death; Cell Line, Tumor; Cell Proliferation; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Dioxoles; Down-Regulation; Humans; Lignans; Lung Neoplasms; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction

The autoclave extraction of Hungarian oak (Quercus

Topics: Chloroform; Dioxoles; Gallic Acid; Lignans; Mannose; Plant Extracts; Quercus; Ribose; Solubility; Water; Wood

Depression is a mood disorder that is related to neuroinflammation and cognition loss. This study is aimed to determine the potential antidepressant effects of (+)-sesamin, a lignan component of sesame, in a mild stress-induced depression mouse model. CD-1 mice were treated with chronic unpredictable mild stress (CUMS) process and orally administrated with sesamin (50 mg/kg/d) for 6 weeks. Behavioral tests including forced swimming test, tail suspension test, open field test, and elevated plus maze test demonstrated that sesamin treatment inhibited CUMS-induced mice depressant-like behaviors and anxiety, without changing immobility. It was found that sesamin prevented stress-induced decease levels of 5-HT and NE in striatum and serum. Cognitive deficits were assessed using Y-maze and Morris water maze test. Sesamin treatment also prevented stressed-induced memory impairments and neuronal damages. Consistently, sesamin also enhanced synapse ultrastructure and improved expressions of PSD-95 in stressed mice hippocampus with improving neurotrophic factors expression including BDNF and NT3. Moreover, sesamin treatment significantly prevented CUMS-induced neuroinflammation by inhibiting over-activation of microglia and expressions of inflammatory mediators including iNOS, COX-2, TNF-α and IL-1β in stressed mice hippocampus and cortex. These results illustrated that sesamin markedly improved CUMS-induced depression and memory loss via inhibiting neuroinflammation, which indicate that as food component, sesamin might be also a novel potential therapeutic for depression.

Topics: Animals; Antidepressive Agents; Behavior, Animal; Brain; Cytokines; Depression; Dietary Supplements; Dioxoles; Disease Models, Animal; Inflammation; Lignans; Male; Maze Learning; Memory Disorders; Mice, Inbred Strains; Nerve Tissue Proteins; Norepinephrine; Serotonin

Abdominal aortic aneurysm (AAA) is a vascular disease characterized by the weakening of the vascular walls and the progressive dilation of the abdominal aorta. Nicotine, a primary component of cigarette smoke, is associated with AAA development and rupture. Nicotine induces AAA development by weakening vascular walls. However, little is known about preventive methods using functional food factors for nicotine-induced vascular destruction. Sesamin and sesamolin are functional food factors that are fat-soluble lignans found in Sesamum indicum seeds. Previous reports indicated that sesamin and sesamolin have anti-oxidative and anti-inflammatory effects. In this study, we evaluated the effects of sesamin and sesamolin-rich sesame extract on the weakening of vascular walls in nicotine-administered mice. Sesame extract attenuated the degradation of collagen and elastin fibers caused by nicotine. In addition, sesame extract decreased the area positive for matrix metalloproteinase 12 (MMP-12) and oxidative stress in the vascular walls. These results suggest that sesame extract may decrease the weakening of vascular walls by suppressing the nicotine-induced degradation of collagen and elastin fibers. Sesame extract may be effective in preventing AAA development by decreasing both, MMP-12 expression and oxidative stress in vascular walls.

Topics: Animals; Aorta, Thoracic; Aortic Aneurysm, Abdominal; Body Weight; Collagen; Dioxoles; Eating; Elastin; Lignans; Male; Matrix Metalloproteinase 12; Mice, Inbred C57BL; Nicotine; Oxidative Stress; Plant Extracts; Sesamum

The determination of the absolute configuration of natural products still faces many challenges, especially the active pharmaceutical ingredient which is trace, oily and novel structures. Currently, NMR requires chiral reagents in determining the absolute configuration; ECD involves theoretical calculations and requires chromophores. In this study, the absolute configuration of asarinin had successfully identified by using synchrotron radiation with crystalline sponge method and combining MS with NMR. This method could identifying the crystal structure of trace amorphous substances, resolving the problem of absolute configuration of multi-chiral central compounds, and hopefully providing a new idea and approach for structural elucidation of natural products.

Topics: Asarum; Biological Products; China; Dioxoles; Lignans; Magnetic Resonance Spectroscopy; Mass Spectrometry; Models, Molecular; Phytochemicals; Synchrotrons

Sesamin is a major lignan constituent of sesame and possesses various health-promoting effects. Previous studies have demonstrated that sesamin extends the lifespan of Drosophila and Caenorhabditis elegans and corrects oxidative damage-related tissue dysfunction in mammals. To understand its anti-aging effects, we aimed to determine whether sesamin restores tissue function hampered by oxidative damage and suppresses several aging-related phenotypes using Drosophila senescence-accelerated models.. We elucidated the anti-aging effects of sesamin on several aging-related phenotypes in the muscle, brain and midgut using the senescence-accelerated models (Sod1n1 mutant and Sod1-depleted flies) by immunostaining experiments. We determined the expression levels of several anti-oxidative and DNA repair genes using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). We also identified the metabolite of sesamin in Drosophila by LC-MS/MS.. We confirmed that sesamin (0.35 and 2 mg/ml) extended the lifespan of the fly models. As observed in mammals, it can be absorbed and metabolized by Drosophila adults. The sesamin feeding suppressed the age-dependent impairment of locomotor activity and inhibited the accumulation of reactive oxygen species (ROS) in their bodies. Sesamin delayed the age-dependent accumulation of damaged proteins in the muscle, partially suppressed the loss of dopaminergic neurons in adult brains displaying ROS accumulation, and suppressed the accumulation of DNA damage and hyperproliferation of intestinal stem cells. Four antioxidative genes and two DNA repair genes were simultaneously upregulated in sesamin-fed adults.  CONCLUSIONS: These observations represent the first direct evidence of the anti-aging effects of sesamin at the individual level. We propose that sesamin exerts anti-aging effects in the muscles, brain and midgut by inducing antioxidative and DNA repair genes, resulting in extended lifespan in flies.

Topics: Aging; Animals; Antioxidants; Cells, Cultured; Chromatography, Liquid; Dioxoles; Disease Models, Animal; Drosophila melanogaster; Drosophila Proteins; Intestines; Lignans; Longevity; Muscles; Nervous System; Phenotype; Superoxide Dismutase; Tandem Mass Spectrometry

Sesamin and sesamolin constitute the main bioactive secondary metabolites of sesame seeds (Sesamum indicum L., Pedaliaceae). In the present work, a rapid HPTLC-based methodology was developed in compliance with the requirements of the European Pharmacopoeia for the quantification of these two lignans in sesame seeds. A comparative study was simultaneously performed with HPLC-PDA for assessing the sesamin and sesamolin content of diverse samples. Both methods were validated and the results were subsequently subjected to statistical analysis in order to compare their performance as well as to investigate possible correlations. The methods were shown to be adequately correlated in terms of performance, as revealed by Pearson's rank correlation coefficients (>0.99 for sesamin and >0.98 for sesamolin) and Bland-Altman analysis (relative method bias 0.06-0.21, SD of bias 0.05-0.07). HPTLC densitometry could thereby serve as a valid and reliable tool for the rapid determination of the major lignans in sesame seed samples.

Topics: Chromatography, High Pressure Liquid; Densitometry; Dioxoles; Lignans; Seeds; Sesamum

Topics: Animals; Anti-Inflammatory Agents; Catechol O-Methyltransferase; Catechols; Cell Line; Cytochrome P-450 Enzyme System; Dioxoles; Glucuronidase; Glucuronides; Interferon-beta; Lignans; Macrophages; Mice; Molecular Structure; Nitric Oxide Synthase Type II

Ten sesame genotypes planted under two irrigation regimes of 60% and 90%, as the maximum allowable depletion (MAD), were used to investigate the effects of drought stress on certain quantitative and qualitative characters of sesame seeds with four contrasting coat colors. The polyphenolic components, sesamin, sesamolin, total flavonoid content (TFC), total phenolic content (TPC), radical scavenging activity (RSA), seed yield, and oil content of the seeds were also examined. Results revealed that drought decreased seed yield, oil content, sesamin, and quercetin but increased TFC, TPC, and RSA as well as most of polyphenolic components and sesamolin. The drought-tolerant genotypes including Markazi1 exhibited higher chlorogenic, ellagic, and p-coumaric acids as well as TFC, RSA, and rutin. While the dark-seeded sesame genotypes contained higher caffeic, ferulic, ellagic acids as well as TPC and RSA, the light-seeded ones were richer in sesamin and sesamolin as well as p-coumaric and gallic acids. The findings of the study provided basic information on the changes in some seed secondary metabolites when sesame was subjected to drought stress. The results also confirmed not only the presence of considerable amounts of antioxidants in sesame seeds but also differences in secondary metabolite levels among the sesame seeds with different seed coat colors.

Topics: Antioxidants; Dioxoles; Droughts; Flavonoids; Free Radical Scavengers; Genotype; Lignans; Phenols; Pigments, Biological; Polyphenols; Seeds; Sesamum

Accumulation of amyloid-β peptide is associated with Alzheimer's dementia. Previously, we reported that sesamin and sesamolin inhibited β-secretase activity in vitro, and each was transported to the serum and brain in mice after oral administration. However, the bioavailability of sesamin and sesamolin was poor in mice. In this study, we aimed to improve the bioavailability of sesamin and sesamolin. We found that the levels of sesamin and sesamolin in mouse serum and brain were higher after the administration of a mixture of sesame extract and turmeric oil (MST) than those after administering sesame extract alone. Serum sesamin and sesamolin contents in the MST-treated group were 23-fold and 15-fold higher, respectively, than those in the sesame extract-treated group. Brain sesamin and sesamolin contents in the MST-treated group were 14-fold and 11-fold higher, respectively, than those in the sesame extract-treated group. These results suggest that turmeric oil is an effective solvent to enhance the bioavailability of sesamin and sesamolin.

Topics: Administration, Oral; Animals; Biological Availability; Brain; Dioxoles; Lignans; Male; Mice; Molecular Conformation; Oils, Volatile; Solubility; Solvents

To study the role of asarinin on collagen-induced arthritis (CIA) and its treatment mechanism on dendritic cells (DCs) and T cells. Before the onset of arthritis, asarinin were given orally to CIA mouse. Macroscopic scoring and micrometer caliper measurement were used to assess arthritis. The occurrence of cartilage destruction and bone erosion were assessed by histology of knee. Sandwich enzyme-linked immunosorbent assay (ELISA) and PCR were used to assess the level of cytokines in hindpaw and arthritic joint. The CD11c MicroBeads were employed to isolate CD11c+ cells from the spleen. Quantitative PCR was used to determine DCs surface molecules of spleen. Macroscopic score and the frequency of arthritis were inhibited by asarinin. Swelling of hindpaws, inflammatory cell infiltration in the synovium, cartilage destruction, and bone erosion were delayed with asarinin. Asarinin treatment suppressed the expression of T helper type 1 (Th1) cytokines and increased the levels of Th2 cytokines (interleukin (IL)-10), transforming growth factor (TGF)-β and Foxp3 in the synovium and hindpaw, however T-bet mRNA levels in synovium decreased. Lower expression of toll-like receptor 9 (TLR9) and nuclear factor-kappaB (NF-κB) were found in DCs after asarinin treatment. There was no difference in the expression of intercellular cell adhesion molecule-1(ICAM-1), OX40-L, and 4-1BBL in spleen DCs between the asarinin group and model control group. Asarinin can treat CIA. TLR9/NF-κB pathway may be involved in the asarinin treatment of CIA by skewing the balance of Th1/Th2/regulatory T (Treg) to a Th2 type.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Cytokines; Dioxoles; Down-Regulation; Knee Joint; Lignans; Male; Mice, Inbred DBA; NF-kappa B; T-Lymphocytes, Regulatory; Th1 Cells; Th2 Cells; Toll-Like Receptor 9

Hippocampal oxidative stress and apoptosis of CA1 neurons play significant roles in the pathophysiology of diabetes-associated cognitive decline (DACD). The present study was aimed to elucidate the putative effects of sesamin, a major lignan of sesame seed, against DACD, and possible involvement of anti-oxidative and anti-apoptotic mechanisms.. Fifty adult male Wistar rats were randomly divided into control, control-sesamin (30 mg/kg/day), diabetic, diabetic-sesamin (30 mg/kg/day), and diabetic-insulin (6 IU/rat/day) groups. Diabetic rats were treated with sesamin (P.O.) or insulin (S.C.) for eight consecutive weeks. Cognitive performance was evaluated in a Morris Water Maze (MWM) test; in addition, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) concentrations were assayed in the hippocampus using assay kits. Moreover, hematoxylin-eosin (HE), TUNEL, and immunohistochemistry (IHC) stainings were conducted to evaluate histological changes, the apoptosis status and expression of pro- and anti-apoptotic proteins in the hippocampal CA1 neurons, respectively.. The results showed that diabetes reduced the spatial cognitive ability in MWM, which was accompanied by decrease in SOD, CAT, and GPx activities and increase in MDA level in the hippocampus. Additionally, diabetes resulted in neuronal loss, enhanced apoptotic index, elevated the expression of pro-apoptotic Bax protein, and decreased the expression of anti-apoptotic Bcl-2 protein in the hippocampal CA1 neurons. Interestingly, sesamin treatment improved all the above-mentioned deficits of diabetes at a comparable level with insulin therapy.. The results suggest that sesamin could be a promising potential therapeutic agent against DACD, possibly through its intertwined anti-hyperglycemic, anti-oxidative, and anti-apoptotic properties.

Topics: Animals; Antioxidants; Apoptosis; Cognitive Dysfunction; Diabetes Complications; Diabetes Mellitus, Experimental; Dioxoles; Glutathione Peroxidase; Hippocampus; Insulin; Lignans; Male; Malondialdehyde; Oxidative Stress; Protective Agents; Rats; Rats, Wistar; Reactive Oxygen Species; Superoxide Dismutase

Sesamin is a furofuran-type lignan that is found abundantly in seeds of Sesamum indicum (sesame) and has been widely accepted as a dietary supplement with positive effects on human health. The biological activity of sesamin in human cells and organs has been analysed extensively, although comparatively few studies show biological functions for sesamin in planta. Herein we screened sesamin-binding proteins (SBP) from sesame seedling extracts using sesamin-immobilized nano-beads. In subsequent peptide mass fingerprinting analyses, we identified a SBP, Steroleosin B, which is one of the membrane proteins found in oil bodies. In addition, pull-down assays and saturation transfer difference-nuclear magnetic resonance (STD-NMR) experiments demonstrated that sesamin binds directly to recombinant Steroleosin B in vitro. Finally, ectopic accumulations of sesamin and Steroleosin B in transgenic Arabidopsis thaliana plants induced severe growth defects including suppression of leaf expansion and root elongation. Collectively, these results indicate that sesamin influences tissue development in the presence of Steroleosin B.

Topics: Arabidopsis; Carrier Proteins; Dioxoles; Germination; Lignans; Plant Development; Plant Proteins; Plants, Genetically Modified; Proton Magnetic Resonance Spectroscopy; Seeds

BACKGROUND Osteoporosis is a common osteopathy, resulting in fractures, especially in elder people. Sesamin has many pharmacological effects, including supplying calcium. However, how sesamin might prevent osteoporosis is still under study. MATERIAL AND METHODS Bone marrow stromal cells (BMSCs) extracted from rat femur were induced for osteoblastic differentiation. Cell proliferation, alkaline phosphatase (ALP), osterix (OSX), SRY-box 9 (SOX9), runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), ß-catenin, low density lipoprotein receptor-related protein 5 (LRP5), and glycogen synthase kinase-3ß (GSK-3ß) levels in BMSCs were detected in the presence or absence of sesamin (1 μM or 10 µM). In addition, FH535 (1 μM) was used to silence Wnt/ß-catenin in vitro. Ovariectomized (OVX) rats were established and intragastrically administrated sesamin (80 mg/kg), and then the rat bones were analyzed by micro-computed tomography. Osteocalcin and collagen type I were measured in the rat femurs. RESULTS Sesamin had no influence on BMSC proliferation. Higher sesamin concentration promoted Wnt/ß-catenin activity and enhanced more expressions of ALP, OSX, SOX9, RUNX2, and OCN, gradually and significantly (P<0.05). Silencing Wnt/ß-catenin weakened the enhancement on RUNX2 and OCN expression. Sesamin (80 mg/kg) promoted bone structure in ovariectomized rats, and significantly enhanced osteocalcin and collage type I expression (P<0.05). CONCLUSIONS Sesamin promoted osteoblastic differentiation of rat BMSCs by regulating the Wnt/ß-catenin pathway, and improved rat bone structure. Sesamin could have therapeutic and preventive effects on osteoporosis.

Topics: Alkaline Phosphatase; Animals; beta Catenin; Bone and Bones; Cell Differentiation; Cell Proliferation; China; Collagen Type I; Dioxoles; Female; Lignans; Mesenchymal Stem Cells; Osteoblasts; Osteocalcin; Osteogenesis; Osteoporosis; Ovariectomy; Rats; Rats, Sprague-Dawley; Wnt Signaling Pathway

A new pair of sesamin-type lignan enantiomers (±)-morifolia A (1a/1b) together with eight known analogues (2-9) were isolated from the fruits of Morinda citrifolia. Their structures were established by spectroscopic data and the absolute configurations of 1a/1b were determined by ECD calculation. All compounds were examined for their inhibitory effects on the nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages, and compounds 1a, 1b, 2-4 and 7-9 exhibited pronounced inhibition with IC

Topics: Animals; Cell Line; Circular Dichroism; Dioxoles; Fruit; Inhibitory Concentration 50; Lignans; Lipopolysaccharides; Macrophages; Magnetic Resonance Spectroscopy; Mice; Molecular Structure; Morinda; Nitric Oxide; Stereoisomerism

Warfarin is a commonly used anticoagulant drug and is a derivate of coumarin. Cytochrome P450 2C9 (CYP2C9) plays the key role in transformation of coumarin and thus, influences determination of warfarin dosage. A number of factors including dietary compounds such as sesamin, caffeic acid and ferulic acids can regulate the activity of CYP2C9. The present study tested the hypothesis that sesamin, episesamin, caffeic acid and ferulic acid decreases the rate of warfarin 7-hydroxylation via inhibition of hepatic CYP2C9. The experiments were conducted on hepatic microsomes from human donors. It was demonstrated that the rate of 7-hydroxylation of warfarin was significantly decreased in the presence of sesamin in the range of concentrations from 5 to 500 nM, and was not affected by episesamin, caffeic acid and ferulic acid in the same range of concentrations. The kinetic analysis indicated non-competitive type of inhibition by sesamin with Ki = 202 ± 18 nM. In conclusion, the results of our in vitro study revealed that sesamin was able to inhibit formation of a major metabolite of warfarin, 7-hydroxywarfarin. The potentially negative consequences of the consumption of high amounts of sesamin-containing food or dietary supplements in warfarin-treated patients need to be further studied.

Topics: Anticoagulants; Caffeic Acids; Coumaric Acids; Dietary Supplements; Dioxoles; Female; Food; Humans; Hydroxylation; Inhibitory Concentration 50; Kinetics; Lignans; Male; Microsomes, Liver; Warfarin

　Sesamin, derived from sesame seeds, is known to have various biological effects. Since some of these effects appear to be derived from its metabolites, the elucidation of sesamin metabolism is essential to understanding the molecular mechanism of its effects. In addition, it is important to clarify drug-sesamin interactions in order to address safety concerns, as some food factors are known to affect drug metabolism. Our previous studies revealed that sesamin was sequentially metabolized by cytochrome P450 (CYP) and UDP-glucuronosyltransferase or sulfotransferase. Whereas sesamin metabolism is mainly mediated by CYP2C9 in human liver, sesamin causes a mechanism-based inhibition (MBI) of CYP2C9. However, we found that the metabolite-intermediate complex between CYP2C9 and sesamin was unstable, and the effects of sesamin appeared to be minimal. To confirm this assumption, in vivo studies using rats were conducted. After the administration of sesamin to rats for 3 d, diclofenac (an NSAID) was administered to measure the time course of plasma concentration of diclofenac. No significant differences were observed in the diclofenac C

Topics: Animals; Cytochrome P-450 CYP2C9; Cytochrome P-450 CYP2C9 Inhibitors; Diclofenac; Dioxoles; Drug Interactions; Humans; Lignans; Rats

Sesamin, a major lignan of sesame oil, has demonstrated anticancer properties. However, its anticancer effects on cervical cancer have not been studied. Here, we investigated the effects of sesamin on cervical cancer (HeLa) cell line and explored the underlying mechanisms.. HeLa cells were cultured with sesamin. CCK-8 and scratch wound test were applied to detect the proliferation and migration ability, while flow cytometry and TUNEL staining were applied to detect apoptosis. The expression of Bax and Bcl-2 was assessed by Western blotting. Further observe the ultrastructure using transmission electron microscopy (TEM) and detect the expression of caspase-12, GRP78, GADD153, IRE1α, p-IRE1α, JNK, p-JNK, LC3I/II and beclin-1. In addition, HeLa cells were treated with 3-MA (an autophagy inhibitor) and/or sesamin. Then detect the expression of LC3I/II and cell viability.. CCK-8 and scratch wound test revealed that sesamin inhibits HeLa cells proliferation and migration, while flow cytometry and TUNEL staining indicated that sesamin induces apoptosis in these cells. In sesamin group, the expression of Bax, caspase-12, GRP78, GADD153, p-IRE1α, p-JNK, LC3I/II and beclin-1 was up-regulated while Bcl-2 was down-regulated compared to control group. Further research revealed that sesamin also induces Hela cells autophagy and inhibition of autophagy increases cell viability of sesamin-treated HeLa cells.. Sesamin inhibits proliferation/migration of HeLa cells and induces ER stress-mediated apoptosis through IRE1α/JNK pathway, and that it activates autophagy and autophagic death in these cells, further validate the anticancer effect of sesamin.

Topics: Apoptosis; Autophagy; Cell Movement; Cell Proliferation; Dioxoles; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Female; Gene Expression Regulation, Neoplastic; HeLa Cells; Humans; Lignans; Neoplasm Proteins; Uterine Cervical Neoplasms

The aim of this study is to disclose the potential bioactive components of Cuscuta palaestina, a native parasitic natural plant of flora palaestina and to open direction towards new prospective application. GC-MS analysis identified 18 components in the methanolic extract of C. palaestina for the first time. The most appealing among them are Sesamin and two other phytosterols (Campesterol and Stigmasterol), all of which are documented in the scientific literature for their anticancer activity. Quantitation of Sesamin extracted from C. palaestina by HPLC-PDA with the use of three organic solvents showed that the Sesamin content in the methanolic extract was the highest. Following the disclosure of Sesamin presence in C. palaestina, we raised the question of whether it is produced naturally in C. palaestina or acquired from the host plant. The quantitation of Sesamin in C. palaestina was performed while being with five different host plants, and was compared with the amount of Sesamin in C. palaestina grown alone. The findings reveal that Sesamin is an endogenous secondary metabolite in C. palaestina. Thus, further studies are required to prove if C. palaestina can be used as an alternative source of anticancer phytochemicals, mainly Sesamin, and if proteins in the Sesamin production pathway could be valid biological targets for the development of novel and selective pesticides for control/ eradication of C. palaestina and maybe some other Cuscuta species. As well, the findings from this study raise a big question of whether inferring Sesamin production in C. palaestina could reduce its attack ability to host plants.

Topics: Calibration; Cuscuta; Dioxoles; Gas Chromatography-Mass Spectrometry; Lignans

The treatment of wood wastes of

Topics: Dioxoles; Gas Chromatography-Mass Spectrometry; Industrial Waste; Larix; Lignans; Molybdenum; Phenols; Phosphoric Acids; Plant Extracts; Quercus; Wood

Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized by β-amyloid (Aβ) plaques in the brain. At the present, there is no approved drug with a proven disease-modifying effect. Sesame seed (Sesame indicum) has long been known as a healthy food in Southeast Asian countries. Sesame lignans obtained from sesame seed possess antioxidant property that exhibit a variety of beneficial effects in various models. The objective of this study was to investigate the protective effects of sesame lignans including sesamin, sesamolin, and sesamol against Aβ toxicity in Caenorhabditis elegans (C. elegans) model of Aβ toxicity and to address whether these sesame lignans have a positive effect on lifespan extension. A transgenic C. elegans expressing human Aβ was used to investigate protective effects of sesame lignans against Aβ toxicity. Sesamin and sesamolin significantly alleviated Aβ-induced paralysis. The real-time PCR revealed that both sesamin and sesamolin did not affect the expression of Aβ transgene. However, we found that only sesamin inhibited Aβ oligomerization. These findings demonstrated that, among three sesame lignans tested, sesamin protected against Aβ toxicity by reducing toxic Aβ oligomers. Sesamin and sesamolin also significantly improved Aβ-induced defect in chemotaxis behavior and reversed the defect to normal. Moreover, sesamin prolonged median and mean lifespan of the wild type worm. On the other hand, sesamolin and sesamol failed to extend lifespan. These results offer valuable evidence for the future use of sesamin in the development of agents for the treatment of AD. It is also worth investigating the structure-activity relationship of lignan-related structures and their anti-Aβ toxicity activities in the future.

Topics: Amyloid beta-Peptides; Animals; Animals, Genetically Modified; Benzodioxoles; Caenorhabditis elegans; Chemotaxis; Dioxoles; Lignans; Longevity; Neurons; Paralysis; Phenols; Protein Multimerization; Transgenes

Acute kidney injury (AKI) is considered a major public health concern in today's world. Sepsis-induced AKI is large as a result of exposure to lipopolysaccharide (LPS) that is the major outer membrane component of Gram-negative bacteria. Sesamin is the main lignan of sesame seeds with multiple protective effects.. In this research, we tried to demonstrate the protective effect of sesamin pretreatment in LPS-induced mouse model of AKI.. LPS was injected at a single dose of 10 mg/kg (i.p.) and sesamin was given p.o. at doses of 25, 50, or 100 mg/kg, one hour prior to LPS.. Treatment of LPS-challenged mice with sesamin reduced serum level of creatinine and blood urea nitrogen (BUN) and returned back renal oxidative stress-related parameters including glutathione (GSH), malondialdehyde (MDA), and activity of catalase and superoxide dismutase (SOD). Moreover, sesamin alleviated inappropriate changes of renal nuclear factor-kappaB (NF-κB), toll-like receptor 4 (TLR4), cyclooxygenase-2 (COX2), tumor necrosis factor α (TNFα), interleukin-6, DNA fragmentation (an apoptotic index), and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). In addition, sesamin diminished magnitude of kidney tissue damage due to LPS.. In summary, sesamin could dose-dependently abrogate LPS-induced AKI via attenuation of renal oxidative stress, inflammation, and apoptosis.

Topics: Acute Kidney Injury; Animals; Antioxidants; Apoptosis; Cytokines; Dioxoles; Disease Models, Animal; Inflammation; Kidney Function Tests; Lignans; Lipopolysaccharides; Male; Mice, Inbred C57BL; Oxidative Stress

Topics: Alcohol Oxidoreductases; Asarum; Cloning, Molecular; Dioxoles; Eugenol; Gene Expression Profiling; Gene Expression Regulation, Plant; Gene Ontology; Lignans; Metabolic Networks and Pathways; Phylogeny; Plant Leaves; Plant Proteins; Plant Roots; Recombinant Proteins; Rhizome

Sesamin, a polyphenolic compound found in sesame seeds, has been reported to exert a variety of beneficial health effects. We have previously reported that sesamin increases the lifespan of Caenorhabditis elegans. In this study, we investigated the molecular mechanisms underlying the longevity effect of sesamin in C. elegans.. Starting from three days of age, Caenorhabditis elegans animals were fed a standard diet alone or supplemented with sesamin. A C. elegans genome array was used to perform a comprehensive expression analysis. Genes that showed differential expression were validated using real-time PCR. Mutant or RNAi-treated animals were fed sesamin, and the lifespan was determined to identify the genes involved in the longevity effects of sesamin.. The microarray analysis revealed that endoplasmic reticulum unfolded protein response-related genes, which have been reported to show decreased expression under conditions of SIR-2.1/Sirtuin 1 (SIRT1) overexpression, were downregulated in animals supplemented with sesamin. Sesamin failed to extend the lifespan of sir-2.1 knockdown animals and of sir-2.1 loss-of-function mutants. Sesamin was also ineffective in bec-1 RNAi-treated animals; bec-1 is a key regulator of autophagy, and is necessary for longevity induced by sir-2.1 overexpression. Furthermore, the heterozygotic mutation of daf-15, which encodes the target of rapamycin (TOR)-binding partner Raptor, abolished lifespan extension by sesamin. Moreover, sesamin did not prolong the lifespan of loss-of-function mutants of aak-2, which encodes the AMP-activated protein kinase (AMPK).. Sesamin extends the lifespan of C. elegans through several dietary restriction-related signaling pathways, including processes requiring SIRT1, TOR, and AMPK.

Topics: AMP-Activated Protein Kinases; Animals; Antioxidants; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Caloric Restriction; Dietary Supplements; Dioxoles; Food Additives; gamma-Cyclodextrins; Gene Expression Profiling; Gene Expression Regulation, Developmental; Gene Knockdown Techniques; Intrinsically Disordered Proteins; Lignans; Mutation; Oligonucleotide Array Sequence Analysis; RNA Interference; Sirtuins; Survival Analysis; TOR Serine-Threonine Kinases

Diabetes is a risk factor that increases the occurrence and severity of cardiovascular events. Cardiovascular complications are the leading cause of mortality of 75% of patients with diabetes >40 years old. Sesamin, the bioactive compound extracted from Sesamum indicum, is a natural compound that has diverse beneficial effects on hypoglycemia and reducing cholesterol. The aim of this study is to investigate sesamin effects to diabetes-inducing cardiac hypertrophy. In the present study bioinformatics analysis demonstrated cardiac hypertrophy signaling may be the most important pathway for upregulating genes in sesamin-treated groups. To verify the bioinformatics prediction, sesamin was used as the main bioactive compound to attenuate the impact of diabetes induced by streptozotocin (STZ) on cardiac function in a rat model. The results revealed that oral administration of sesamin for 4 weeks (100 and 200 mg/kg body weight) marginally improved blood glucose levels, body weight and significantly ameliorated the effects on heart rate and blood pressure in rats with type 1 diabetes relative to control rats. The QT interval of sesamin was also reduced relative to the control group. The findings indicated that sesamin has potential cardioprotective effects in the STZ-induced diabetes model. This suggested that this can be used as a novel treatment for patients with diabetes with cardiac dysfunction complication.

Topics: Administration, Oral; Animals; Blood Glucose; Blood Pressure; Body Weight; Cardiomegaly; Diabetes Mellitus, Experimental; Dioxoles; Electrocardiography; Heart; Heart Rate; Lignans; Male; Myocardium; Rats; Rats, Sprague-Dawley; Streptozocin

This study investigated the effects of asarinin on dopamine biosynthesis and 6-hydroxydopamine (6-OHDA)-induced cytotoxicity in rat adrenal pheochromocytoma (PC12) cells. Treatment with asarinin (25-50 μM) increased intracellular dopamine levels and enhanced L-DOPA-induced increases in dopamine levels. Asarinin (25 μM) induced cyclic AMP-dependent protein kinase A (PKA) signaling, leading to increased cyclic AMP-response element binding protein (CREB) and tyrosine hydroxylase (TH) phosphorylation, which in turn stimulated dopamine production. Asarinin (25 μM) also activated transient phosphorylation of extracellular signal-regulated kinase (ERK1/2) and Bad phosphorylation at Ser 112, both of which have been shown to promote cell survival. In contrast, asarinin (25 μM) inhibited sustained ERK1/2, Bax, c-Jun N-terminal kinase (JNK1/2) and p38 mitogen-activated protein kinase (p38MAPK) phosphorylation and caspase-3 activity, which were induced by 6-OHDA (100 μM). These results suggest that asarinin induces dopamine biosynthesis via activation of the PKA-CREB-TH system and protects against 6-OHDA-induced cytotoxicity by inhibiting the sustained activation of the ERK-p38MAPK-JNK1/2-caspase-3 system in PC12 cells.

Topics: Animals; Asarum; Cell Survival; Cells, Cultured; Dioxoles; Dopamine; Dose-Response Relationship, Drug; Lignans; Molecular Structure; Oxidopamine; PC12 Cells; Rats; Structure-Activity Relationship

Worldwide, the most recognized musculoskeletal degenerative disease is osteoarthritis (OA). Sesamin, a major abundant lignan compound present in Sesamun Indicum Linn, has been described for its various pharmacological effects and health benefits. However, the promoting effects of sesamin on chondrogenic differentiation have not yet been observed. Herein, the aim of this study was to investigate the effects of sesamin on cell cytotoxicity and the potent supporting effects on chondrogenic differentiation of human amniotic fluid-derived mesenchymal stem cells (hAF-MSCs). The results indicated that sesamin was not toxic to hAF-MSCs after sesamin treatment. When treating the cells with a combination of sesamin and inducing factors, sesamin was able to up-regulate the expression level of specific genes which play an essential role during the cartilage development process, including SOX9, AGC, COL2A1, COL11A1, and COMP and also simultaneously promote the cartilage extracellular protein synthesis, aggrecan and type II collagen. Additionally, histological analysis revealed a high amount of accumulated sGAG staining inside the porous scaffold in the sesamin co-treating group. In conclusion, the results of this study have indicated that sesamin can be considered a chondrogenic inducing factor and a beneficial dietary supplement for cartilage repair.

Topics: Amniotic Fluid; Antioxidants; Cell Differentiation; Cell Survival; Chondrogenesis; Dioxoles; Flow Cytometry; Gene Expression Regulation, Developmental; Humans; Lignans; Mesenchymal Stem Cells

The aim of the present study was to evaluate in vitro effects of dietary phytochemicals naringenin, quercetin, and sesamin on the activities of ethoxy- (EROD; CYP1A) and benzyloxy- (BROD; CYP3A) resorufin O-dealkylases after the exposure to the cocktail of persistent organic pollutants (POPs). CD-1 mice were exposed from weaning, through gestation and lactation to a defined mixture of POPs. Hepatic microsomes were prepared from their female offspring at postnatal day 42. Hepatic EROD and BROD activity were evaluated in the presence of quercetin, naringenin, and sesamin at nine concentrations from 5 to 100000 nM. EROD activity was strongly inhibited by quercetin with

Topics: Air Pollutants; Animals; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Cytochrome P450 Family 1; Dioxoles; Female; Flavanones; Lignans; Maternal Exposure; Mice; Microsomes, Liver; Pregnancy; Prenatal Exposure Delayed Effects; Quercetin

Numerous studies have reported on the health benefits of sesamin, a major lignin found in sesame (S. indicum) seeds. Recently, sesamin was shown to have the ability to promote chondroitin sulfate proteoglycan synthesis in normal human chondrocytes. This study assesses the anti-inflammatory effect of sesamin on proteoglycans production in 3D chondrocyte cultures.. To evaluate the effects of sesamin on IL-1β-treated human articular chondrocytes (HAC) pellets, the pellets were pre-treated with IL-1β then cultured in the presence of various concentrations of sesamin for 21 days. During that period, the expression of IL-1β, glycosaminoglycans (GAGs) content and Chondroitin sulfate proteoglycans (CSPGs) synthesis genes (ACAN, XT-1, XT-2, CHSY1 and ChPF) was measured. The GAGs accumulation in the extracellular matrix was determined on day 21 by histological analysis.. There was clear evidence that sesamin upregulated expression of all the CSPGs synthesis genes, in contrast to the down-regulation of IL-1β expression both in genes and in protein levels. The level of release and matrix accumulation of GAGs in IL-1β pre-treated HAC pellets in the presence of sesamin was recovered. These results correlate with the histological examination which showed that sesamin enhanced matrix CSPGs accumulation.. Sesamin enhances CSPGs synthesis, suppresses IL-1β expression and ameliorates IL-1β induced inflammation in human chondrocytes. Sesamin could have therapeutic benefits for treating inflammation in osteoarthritis.

Topics: Adult; Aggrecans; Cells, Cultured; Chondrocytes; Chondroitin Sulfate Proteoglycans; Dioxoles; Female; Glucuronosyltransferase; Humans; Interleukin-1beta; Lignans; Male; Middle Aged; Multifunctional Enzymes; N-Acetylgalactosaminyltransferases; Young Adult

Myocardial infarction is a devastating event, especially when reperfusion is not performed. The inflammatory response has been associated with the pathogenesis of left ventricular remodeling after myocardial infarction. This study focused on the anti-apoptotic and anti-inflammatory effects of sesamin on ligation of the left anterior descending artery in an experimental mouse model and the potential mechanism underlying the activation of JNK and NF-κB pathways. Mice with MI induced by surgical left anterior descending coronary artery ligation were treated with sesamin by gavage for 1 week. Results showed that after treatment with sesamin, MI-induced cardiac damage was alleviated significantly, indicated by the histopathological examination. The myocardial apoptosis in the border zone was dramatically reduced by sesamin, resulting from the altered expression of apoptosis factors. Moreover, treatment with sesamin also mitigated the inflammatory response, decreased expression of cytokines and the inactivation of NF-κB (nuclear factor κB) signaling. Sesamin decreased the levels of p-JNK protein, which in turn inactivated pro-apoptotic signaling events by restoring the balance between mitochondrial pro-apoptotic Bcl-2 and Bax proteins. Thus, our study suggests that sesamin could alleviate MI-induced cardiac dysfunction through decrease of myocardial apoptosis and inflammatory response.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Dioxoles; Disease Models, Animal; Humans; Lignans; Male; MAP Kinase Kinase 4; Mice; Myocardial Infarction; NF-kappa B; Plant Extracts; Sesamum; Signal Transduction

Topics: Animals; Apoptosis; Aquaporin 4; Blood-Brain Barrier; Brain Edema; Brain Injuries, Traumatic; Capillary Permeability; Caspase 3; Cell Line; Dioxoles; Disease Models, Animal; Endothelial Cells; Extracellular Signal-Regulated MAP Kinases; Lignans; Male; Mice, Inbred C57BL; Neuroprotective Agents; Occludin; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Time Factors; Zonula Occludens-1 Protein

Sesamin is a well-known antioxidant extracted from sesame seeds that exhibits various curative effects. The present study investigated whether sesamin would protect neuroblastoma SH-SY5Y cells against mechanical stretch injury-induced increases in reactive oxygen species (ROS) and apoptosis. Additionally, the mechanisms underlying these actives were investigated. Following exposure to mechanical stretch injury, cells were incubated for further investigations. Lactate dehydrogenase and Cell Counting Kit-8 assays were used to assess cell viability, and a terminal deoxynucleotidyl transferase dUTP nick end labeling assay and flow cytometric analysis were performed to evaluate changes in mitochondrial membrane potential (ΔΨm). Furthermore, intracellular levels of ROS production were measured by 20, 70-dichlorofluorescein diacetate staining, the mRNA levels of matrix metallopeptidase 9 (MMP-9) were evaluated using real-time polymerase chain reaction analysis, and the determinations had also been made on related proteins by Western blot analysis.. Exposure to mechanical stretch injury significantly decreased cell viability but this decrease was attenuated by pretreatment with sesamin (50 μM). Sesamin also significantly inhibited mechanical stretch injury-induced increases in intracellular ROS production, attenuated declines in ΔΨm, diminished the expressions of pro-apoptotic proteins, and decreased cell apoptosis. Stretch injury increased Bax and cleaved caspase 3 levels, enhanced the gene expression of MMP-9, increased the phosphorylation levels of Akt, p38, and JNK and decreased Bcl-2 levels in the cells. However, pretreatment with sesamin reduced the mechanical stretch injury-induced overexpression of MMP-9.. Sesamin protected SH-SY5Y cells against stretch injury by attenuating increases in ROS levels and suppressing apoptosis. Accordingly, sesamin seems to be a potentially therapeutic agent in the treatment of traumatic brain injury.

Topics: Antioxidants; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Cell Line, Tumor; Cell Survival; Dioxoles; DNA Fragmentation; Humans; Lignans; MAP Kinase Kinase 4; Matrix Metalloproteinase 9; Membrane Potential, Mitochondrial; Neurons; Neuroprotective Agents; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species

Sesamin is a major lignan in sesame seeds and oil. We previously demonstrated that sesamin induces chromosomal aberrations (CA) in Chinese hamster lung (CHL/IU) cells in the presence of a metabolic activation system (S9 mix), although no genotoxicity was detected in vivo. To clarify the mechanism of CA induction by sesamin, we identified its principal active metabolite. A mono-catechol derivative, [2-(3,4-methylenedioxyphenyl)-6-(3,4-dihydroxyphenyl)-3,7-dioxabi-cyclo[3.3.0]octane (SC-1)], was previously identified in culture medium when sesamin was incubated with S9 mix. In the present study, we show that SC-1 induces CA in CHL/IU cells but not in human hepatoblastoma (HepG2) cells. SC-1 was unstable in culture medium. Addition of glutathione (GSH) to the incubation mixture decreased the rate of decomposition and also suppressed induction of CA in CHL/IU cells. These results indicate that SC-1 itself may not contribute to the induction of CA. Two GSH adducts of SC-1 were identified when SC-1 was incubated with GSH, suggesting that SC-1 was converted to the semiquinone/quinone form and then conjugated with GSH in the culture medium. Sodium sulfite (a quinone-responsive compound) also suppressed CA induction by SC-1. These findings strongly suggest that SC-1 is oxidized to semiquinone/quinone derivatives extracellularly in culture medium, that these derivatives are responsible for the induction of CA in CHL/IU cells, and therefore that the positive results obtained with sesamin in in vitro CA tests using CHL/IU cells may not be relevant to the assessment of in vivo activity.

Topics: Animals; Bridged Bicyclo Compounds, Heterocyclic; Cell Culture Techniques; Chromosome Aberrations; Cricetinae; Cyclooctanes; Dioxoles; Dose-Response Relationship, Drug; Glutathione; Hep G2 Cells; Humans; Lignans; Liver; Liver Extracts; Lung

The promotional nature of sesamin on human osteoblast differentiation has been proven. Here, the effect of sesamin on human osteoclasts was investigated in terms of differentiation and function in M-CSF and RANKL induced human PBMCs. Sesamin treatment significantly decreased the number of differentiated osteoclasts observed by TRAP staining; however, sesamin inhibition did not result from the alteration of precursor cell proliferation. Sesamin did not decrease NFATc1 gene expression, which opposed the decreasing trend of CathK and TRAP expression. DC-STAMP, but not Atp6v0d2, also significantly decreased in the presence of 14 µM sesamin. Expressions of CCR2b and CCR4 as chemokine receptors were significantly down-regulated. Sesamin might mediate the inhibition of human osteoclast differentiation, the recruitment of precursor cells and F-actin formation. Decrease in the area of the resorption pits and the collagen released from the bone slices under sesamin treatment emphasized the inhibitory effects on both the differentiation and function of osteoclasts. Sesamin is a promising phytochemical agent inhibiting osteoclast differentiation and function.

Topics: Bone Marrow Cells; Bone Resorption; Cell Culture Techniques; Cell Differentiation; Cell Proliferation; Cells, Cultured; Dioxoles; Gene Expression; Healthy Volunteers; Humans; Lignans; Macrophage Colony-Stimulating Factor; Osteoclasts; Osteogenesis; RANK Ligand

Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic synovitis, cartilage degradation and bone deformities. Synovitis is the term for inflammation of the synovial membrane, an early stage of RA. The pathogenesis of the disease occurs through cytokine induction. The major cytokine that increases the severity of RA is TNF-α. Thus, inhibition of the TNF-α cascade is an effective way to diminish the progression of the disease. We are interested in investigating the difference between primary human synovial fibroblast (hSF) cells and SW982 as synovitis models induced by TNF-α and in monitoring their responses to sesamin as an anti-inflammatory phytochemical.. The designed experiments were performed in hSF cells or the SW982 cell line treated with 10 ng/ml TNF-α with or without 0.25, 0.5 or 1 μM sesamin. Subsequently, pro-inflammatory cytokine genes and proteins were measured in parallel with a study of associated signalling transduction involved in inflammatory processes, including NF-κB and MAPK pathways.. The results demonstrated that although hSF and SW982 cells responded to TNF-α induction in the same fashion, they reacted at different levels. TNF-α could induce IL-6, IL-8 and IL-1β in both cell types, but the levels in SW982 cells were much higher than in hSF cells. This characteristic was due to the different induction of MAPKs in each cell type. Both cell types reacted to sesamin in almost the same fashion. However, hSF cells were more sensitive to sesamin than SW982 cells in terms of the anti-RA effect.. The responses of TNF-α-induced hSF and SW982 were different at the signal transduction level. However, the two cell types showed almost the same reaction to sesamin treatment in terms of the end point of the response.

Topics: Arthritis, Rheumatoid; Cell Line; Cytokines; Dioxoles; Fibroblasts; Humans; Lignans; Models, Biological; Signal Transduction; Synovial Membrane; Synovitis; Tumor Necrosis Factor-alpha

Cardiac remodeling is associated with oxidative stress. Sesamin, a well-known antioxidant from sesamin seeds, have been used extensively as traditional health foods. However, there is little known about the effect of sesamin on cardiac remodeling. Therefore, the present study aimed to determine whether sesamin could protect against cardiac remodeling and to clarify potential molecular mechanisms.. The mice were subjected to either transverse aortic constriction (TAC) or sham surgery (control group). Beginning one week after surgery, the mice were oral gavage treated with sesamin (100mg·kg-1·day-1) or vehicle for 3 weeks. Cardiac hypertrophy was assessed by echocardiographic parameters, histological analyses and hypertrophic markers.. Sesamin alleviated cardiac hypertrophy, inhibited fibrosis and attenuated the inflammatory response. The increased production of reactive oxygen species, the activation of ERK1/2-dependent nuclear factor-κB and the increased level of Smad2 phosphorylation were observed in cardiac remolding model that were treated with sesamin. Furthermore, TAC induced alteration of Sirt3 and SOD2 was normalized by sesamin treatment. Finally, a selective Sirt3 inhibitor 3-TYP blocks all the protective role of sesamin, suggesting that a Sirt3-dependent effect of sesamin on cardiac remodeling.. Sesamin improves cardiac function and prevents the development of cardiac hypertrophy via Sirt3/ROS pathway. Our results suggest the protective effect of sesamin on cardiac remolding.

Topics: Animals; Antioxidants; Cardiomegaly; Dioxoles; Fibrosis; Heart; Inflammation; Lignans; Male; MAP Kinase Signaling System; Mice; Myocardium; Oxidative Stress; Reactive Oxygen Species; Signal Transduction; Sirtuin 3

(+)-Sesamin, (+)-sesamolin, and (+)-sesaminol glucosides are phenylpropanoid-derived specialized metabolites called lignans, and are rich in sesame (Sesamum indicum) seed. Despite their renowned anti-oxidative and health-promoting properties, the biosynthesis of (+)-sesamolin and (+)-sesaminol remained largely elusive. Here we show that (+)-sesamolin deficiency in sesame is genetically associated with the deletion of four C-terminal amino acids (Del4C) in a P450 enzyme CYP92B14 that constitutes a novel clade separate from sesamin synthase CYP81Q1. Recombinant CYP92B14 converts (+)-sesamin to (+)-sesamolin and, unexpectedly, (+)-sesaminol through an oxygenation scheme designated as oxidative rearrangement of α-oxy-substituted aryl groups (ORA). Intriguingly, CYP92B14 also generates (+)-sesaminol through direct oxygenation of the aromatic ring. The activity of CYP92B14 is enhanced when co-expressed with CYP81Q1, implying functional coordination of CYP81Q1 with CYP92B14. The discovery of CYP92B14 not only uncovers the last steps in sesame lignan biosynthesis but highlights the remarkable catalytic plasticity of P450s that contributes to metabolic diversity in nature.

Topics: Biosynthetic Pathways; Cytochrome P-450 Enzyme System; Dioxoles; Furans; Humans; Lignans; Molecular Structure; Mutation; Oxidation-Reduction; Oxidative Stress; Phylogeny; Plant Proteins; Sesamum

Epidemiological studies present the beneficial effects of dietary habits on prevention of aging-associated decline of brain function. Phytochemicals, the second metabolites of food, protect neuronal cells from cell death in cellular models of neurodegenerative disorders, and the neuroprotective activity has been ascribed to the anti-oxidant and anti-inflammatory functions. In this paper, the cellular mechanism of neuroprotection by phytochemicals was investigated, using the cellular model of mitochondrial apoptosis induced by PK11195, a ligand of outer membrane translocator protein, in SH-SY5Y cells. PK11195 induced mitochondrial membrane permeabilization with rapid transit production of superoxide (superoxide flashes) and calcium release from mitochondria, and activated apoptosis signal pathway. Study on the structure-activity relationship of astaxanthin, ferulic acid derivatives, and sesame lignans revealed that these phytochemicals inhibited mitochondrial membrane permeabilization and protected cells from apoptosis. Ferulic acid derivatives and sesame lignans inhibited or enhanced the mitochondrial pore formation and cell death by PK11195 according to their amphiphilic properties, not directly depending on the antioxidant activity. Regulation of pore formation at mitochondrial membrane is discussed as a novel mechanism behind neuroprotective activity of phytochemicals in aging and age-associated neurodegenerative disorders, and also behind dual functions of phytochemicals in neuronal and cancer cells.

Topics: Apoptosis; Calcium; Cations, Divalent; Cell Line, Tumor; Cell Survival; Coumaric Acids; Dioxoles; Humans; Hydrophobic and Hydrophilic Interactions; Isoquinolines; Lignans; Mitochondrial Membrane Transport Proteins; Mitochondrial Membranes; Neuroprotective Agents; Oxygen; Permeability; Phytochemicals; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Xanthophylls

Graphene oxide was fabricated by a simple method and applied to magnetic solid-phase extraction. In a pretreatment procedure before the sesamol, sesamin and sesamolin in sesame oil were detected by high performance liquid chromatography. Several parameters affecting the extraction efficiency were investigated, including the type and volume of desorption solvent, desorption time and the amount of sorbent. Under the optimized conditions, the detection limits of sesamol, sesamin, and sesamolin were 0.05μg/g, 0.02μg/g, and 0.02μg/g, respectively. The limits of quantification were all 0.2μg/g. The average recoveries of sesamol, sesamin, and sesamolin were 84.55%, 85.47%, 86.83%, respectively and their relative standard deviations were 1.23%, 1.33%, and 0.84%, respectively.

Topics: Benzodioxoles; Chromatography, High Pressure Liquid; Dioxoles; Graphite; Lignans; Magnetic Phenomena; Phenols; Sesame Oil; Solid Phase Extraction

Topics: Amides; Apigenin; Benzodioxoles; Catechin; Chromatography, High Pressure Liquid; Coumarins; Dioxoles; Flavonoids; Furans; Hesperidin; Hydroxybenzoates; Lignans; Limit of Detection; Plant Leaves; Powders; Reproducibility of Results; Seasons; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry; Zanthoxylum

Sesamin is a major lignan in sesame seeds and has various physiological effects. Although metabolism of sesamin by cytochrome P450 or intestinal microflora has been reported, little is known concerning the mass balance, pharmacokinetics, and tissue distribution of sesamin.. Sesamin was absorbed efficiently and distributed over the whole body. In particular, sesamin was highly distributed in the form of the metabolites in the liver and kidney. The results of this study are useful in elucidating the action mechanism of sesamin.

Topics: Administration, Intravenous; Administration, Oral; Animals; Bile; Carbon Radioisotopes; Dioxoles; Feces; Lignans; Male; Rats, Sprague-Dawley; Tissue Distribution

This study investigated the effects of (-)-sesamin on chronic electric footshock (EF) stress-induced anxiety disorders in mice. Mice were treated with (-)-sesamin (25 and 50 mg/kg) orally once a day for 21 days prior to exposure to EF stress (0.6 mA, 1 s every 5 s, 3 min). Mice treated with (-)-sesamin (25 and 50 mg/kg) exhibited less severe decreases in the number of open arm entries and time spent on open arms in the elevated plus-maze test and the distance traveled in the open field test following exposure to chronic EF stress. Similarly, mice treated with (-)-sesamin exhibited significantly less severe decreases in brain levels of dopamine, norepinephrine, and serotonin following exposure to chronic EF stress. Increases in serum levels of corticosterone and expression of c-Fos were also less pronounced in mice treated with (-)-sesamin (25 and 50 mg/kg). These results suggest that (-)-sesamin may protect against the effects of chronic EF stress-induced anxiety disorders by modulating dopamine, norepinephrine, and serotonin levels, c-Fos expression, and corticosterone levels.

Topics: Animals; Anti-Anxiety Agents; Antioxidants; Anxiety Disorders; Biogenic Monoamines; Brain; Chronic Disease; Corticosterone; Dioxoles; Lignans; Male; Mice; Mice, Inbred ICR; Stress, Psychological; Treatment Outcome

Interrelated effects of γ-linolenic acid (GLA) and sesamin, a sesame lignan, on hepatic fatty acid synthesis and oxidation were examined. Rats were fed experimental diets supplemented with 0 or 2 g/kg sesamin (1:1 mixture of sesamin and episesamin) and containing 100 g/kg of palm oil (saturated fat), safflower oil rich in linoleic acid, or oil of evening primrose origin containing 43% GLA (GLA oil) for 18 days. In rats fed sesamin-free diets, GLA oil, compared with other oils, increased the activity and mRNA levels of various enzymes involved in fatty acid oxidation, except for some instances. Sesamin greatly increased these parameters, and the enhancing effects of sesamin on peroxisomal fatty acid oxidation rate and acyl-CoA oxidase, enoyl-CoA hydratase and acyl-CoA thioesterase activities were more exaggerated in rats fed GLA oil than in the animals fed other oils. The combination of sesamin and GLA oil also synergistically increased the mRNA levels of some peroxisomal fatty acid oxidation enzymes and of several enzymes involved in fatty acid metabolism located in other cell organelles. In the groups fed sesamin-free diets, GLA oil, compared with other oils, markedly reduced the activity and mRNA levels of various lipogenic enzymes. Sesamin reduced all these parameters, except for malic enzyme, in rats fed palm and safflower oils, but the effects were attenuated in the animals fed GLA oil. These changes by sesamin and fat type accompanied profound alterations in serum lipid levels. This may be ascribable to the changes in apolipoprotein-B-containing lipoproteins.

Topics: Acyl-CoA Oxidase; Animals; Dietary Fats, Unsaturated; Dietary Sucrose; Dietary Supplements; Dioxoles; Enoyl-CoA Hydratase; Fatty Acids; gamma-Linolenic Acid; Gene Expression Regulation, Enzymologic; Hyperlipidemias; Hypolipidemic Agents; Lignans; Linoleic Acids; Lipids; Liver; Male; Oenothera biennis; Oxidation-Reduction; Palm Oil; Peroxisomes; Plant Oils; Rats, Sprague-Dawley; Safflower Oil; Thiolester Hydrolases

The role of inflammation and oxidative stress is critical during onset of metabolic disorders and this has been sufficiently established in literature. In the present study, we evaluated the effects of sesamol and sesamin, two important bioactive molecules present in sesame oil, on the generation of inflammatory and oxidative stress factors in LPS injected rats. Sesamol and sesamin lowered LPS induced expression of cPLA

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Arachidonate 5-Lipoxygenase; Benzodioxoles; Biomarkers; Dietary Supplements; Dioxoles; Glutathione Transferase; Hepatitis; Inflammation Mediators; Leukotriene Antagonists; Leukotrienes; Lignans; Lipid Peroxidation; Lipopolysaccharides; Liver; Male; Oxidative Stress; Phenols; Phospholipases A2, Cytosolic; Rats, Wistar; Receptors, Leukotriene B4; Sesame Oil

Mammalian lignans or enterolignans are metabolites of plant lignans, an important category of phytochemicals. Although they are known to be associated with estrogenic activity, cell signaling pathways leading to specific cell functions, and especially the differences among lignans, have not been explored. We examined the estrogenic activity of enterolignans and their precursor plant lignans and cell signaling pathways for some cell functions, cell cycle and chemokine secretion. We used DNA microarray-based gene expression profiling in human breast cancer MCF-7 cells to examine the similarities, as well as the differences, among enterolignans, enterolactone and enterodiol, and their precursors, matairesinol, pinoresinol and sesamin. The profiles showed moderate to high levels of correlation (R values: 0.44 to 0.81) with that of estrogen (17β-estradiol or E2). Significant correlations were observed among lignans (R values: 0.77 to 0.97), and the correlations were higher for cell functions related to enzymes, signaling, proliferation and transport. All the enterolignans/precursors examined showed activation of the Erk1/2 and PI3K/Akt pathways, indicating the involvement of rapid signaling through the non-genomic estrogen signaling pathway. However, when their effects on specific cell functions, cell cycle progression and chemokine (MCP-1) secretion were examined, positive effects were observed only for enterolactone, suggesting that signals are given in certain directions at a position closer to cell functions. We hypothesized that, while estrogen signaling is initiated by the enterolignans/precursors examined, their signals are differentially and directionally modulated later in the pathways, resulting in the differences at the cell function level.

Topics: 4-Butyrolactone; Cell Cycle; Dioxoles; Estrogens; Furans; Gene Expression Profiling; Humans; Lignans; MCF-7 Cells; Oligonucleotide Array Sequence Analysis; Signal Transduction

Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders in elders. Sesamin is a lignan compound and the active constituent of sesame oil with antioxidant and anti-inflammatory properties. This study was carried out to explore the mechanisms underlying sesamin effect against unilateral striatal 6-hydroxydopamine (6-OHDA) model of PD. Intrastriatal 6-OHDA-lesioned rats were pretreated with sesamin at doses of 10 or 20mg/kg/day for one week. Sesamin at a dose of 20mg/kg attenuated motor imbalance in narrow beam test, lowered striatal level of malondialdehyde (MDA) and reactive oxygen species (ROS), improved superoxide dismutase (SOD) activity, lowered striatal caspase 3 activity and α-synuclein expression, attenuated glial fibrillary acidic protein (GFAP) immunoreactivity, depressed nigral neuronal apoptosis, and prevented damage of dopaminergic neurons using tyrosine hydroxylase (TH) immunohistochemistry. These findings reveal the reversal effect of sesamin in 6-OHDA model of PD via attenuation of apoptosis, astrogliosis, oxidative stress, and down-regulation of α-synuclein.

Topics: Animals; Apoptosis; Astrocytes; Behavior, Animal; Caspase 3; Dioxoles; Gliosis; Lignans; Male; Malondialdehyde; Neostriatum; Neuroprotective Agents; Oxidative Stress; Oxidopamine; Parkinson Disease, Secondary; Postural Balance; Rats; Rats, Wistar; Reactive Oxygen Species; Superoxide Dismutase

To investigate the protective effect of sesamin on myocardial ischemia reperfusion injury in rats, and to study the possible mechanism.. 50 SD rats were randomly divided into control group, sham operated group, model group, high-dose sesamin group( 160 mg / kg) and low-dose sesamin group( 80 mg / kg),with 10 rats in each group. Rats in sesamin groups were administered intragastrically with sesamin for 7 d. Then all rats except those in sham operated group were subjected to myocardial ischemia-myocardial ischemia reperfusion injury model by coronary artery ligation for 40 min and subsequent reperfusion for 120 min. Serum cardiac troponin Ⅰ( c TnⅠ) and lactate dehydrogenase( LDH),levels of total antioxidant capacity( TAOC) and nitric oxide( NO) in serum and myocardial tissues,Caspase-3 activity in myocardial tissues were detected by colorimetric assay. Cardiomyocyte apoptosis was evaluated by TUNEL assay. Phosphorylation level of endothelial nitric oxide synthase( eNOS) and Protein kinase B( Akt), protein expression of superoxide dismutase( SOD) in cardiac tissue were determined by Western blot.. Pretreatment with sesamin significantly ameliorated myocardial injury in rats which induced myocardial ischemia and reperfusion injury by reduced levels of serum c TnⅠand LDH( P <0. 05 or P < 0. 01). Supplementation with sesamin resulted in a significant increasing of total antioxidant capacity and NO level in serum and myocardial tissues and cardiomyocyte apoptosis( P < 0. 05 or P < 0. 01),and remarkable decrease the Caspase-3 activity in myocardial tissues and cardiomyocyte apoptosis( P < 0. 05 or P < 0. 01). Sesamin significantly up-regulated the protein expression of SOD in cardiac tissues, and the levels of phosphorylated eNOS and Akt increased notably( P < 0. 05 or P < 0. 01).. Pretreatment with sesamin effectively ameliorated myocardial ischemia reperfusion injury in rats, and the mechanism might be related to enhancing its antioxidant capacity and the activation of Akt / eNOS signaling pathway and subsequent increase of NO synthesis and suppression of cardiac myocyte apoptosis.

Topics: Animals; Apoptosis; Dioxoles; Heart; L-Lactate Dehydrogenase; Lignans; Myocardial Reperfusion Injury; Myocardium; Nitric Oxide Synthase Type III; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Signal Transduction

Sesamin is known for its role in antioxidant, antiproliferative, antihypertensive, and neuroprotective activities. However, little is known about the role of sesamin in the development of emotional disorders. Here we investigated persistent inflammatory pain hypersensitivity and anxiety-like behaviors in the mouse suffering chronic pain.. Chronic inflammatory pain was induced by hind paw injection of complete Freund's adjuvant (CFA). Levels of protein were detected by Western blot.. Administration of sesamin could induce anxiolytic activities but had no effect on analgesia. In the basolateral amygdala, a structure involving the anxiety development, sesamin attenuated the up-regulation of NR2B-containing N-methyl-d-aspartate receptors, GluR1 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor as well as phosphorylation of GluR1 at Ser831 (p-GluR1-Ser831), and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII-alpha) in the hind paw CFA-injected mice. In the same model, we found that the sesamin blocked the down-regulation of gamma-aminobutyric acid A (GABAA-alpha-2) receptors.. Our findings show that sesamin reduces anxiety-like behaviors induced by chronic pain at least partially through regulating the GABAergic and glutamatergic transmission in the amygdala of mice.

Topics: Animals; Anti-Anxiety Agents; Anxiety; Basolateral Nuclear Complex; Behavior, Animal; Chronic Pain; Dietary Supplements; Dioxoles; Disease Models, Animal; Freund's Adjuvant; Hot Temperature; Hyperalgesia; Lignans; Male; Mice, Inbred C57BL; Nerve Tissue Proteins; Neuralgia; Neuritis; Neurons; Neuroprotective Agents; Phosphorylation; Pressure; Protein Processing, Post-Translational

The purpose of this study was the isolation of metalloproteinases MMP-1 and MMP-9 inhibitors from the chloroform extract of the Eleutherococcus divaricatus roots. Using GC-MS, (1)H and (13)C NMR, HMQC, HMBC, COSY and DEPT, (+)-sesamin has been identified as a new anti-MMP inhibitor. We report for the first time that (+)-sesamin inhibited MMP-1 and MMP-9 activity in 40% and 17%, respectively. The high inhibitory potential has been shown by ursolic acid (90.9% and 89.8% for MMP-1 and MMP-9). In the PAMPA test, the Pe value for sesamin was established as 17.4 × 10(-6) cm/s, that for ursolic acid as 30.0 × 10(- 6) cm/s. Verapamil and theophylline were used as a positive and negative control (Pe 42.1 and 2.9 × 10(-6) cm/s). To our best knowledge, no information was available on this activity of sesamin and other compounds. These studies provide a biochemical basis for the regulation of MMP-1 and MMP-9 by E. divaricatus compounds.

Topics: Dioxoles; Eleutherococcus; Gas Chromatography-Mass Spectrometry; Lignans; Matrix Metalloproteinase 1; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Plant Roots; Solubility; Theophylline; Triterpenes; Ursolic Acid; Verapamil

In 2009, swine flu (H1N1) had spread significantly to levels that threatened pandemic influenza. There have been many treatments that have arisen for patients since the WHO first reported the disease. Although some progress in controlling influenza has taken place during the last few years, the disease is not yet under control. The development of new and less expensive anti-influenza drugs is still needed. Here, we show that sesamin from the seeds of the Thai medicinal plant Sesamum indicum has anti-inflammatory cytokines in human peripheral blood mononuclear cells (PBMCs) induced by 2009 influenza virus type A H1N1. In this study, the combinatorial screening method combined with the computational approach was applied to investigate the new molecular binding structures of sesamin against the 2009 influenza virus type A H1N1 (p09N1) crystallized structure. Experimental methods were applied to propose the mechanisms of sesamin against cytokine production from H1N1-induced human PBMC model. The molecular dynamics simulation of sesamin binding with the p09N1 crystallized structure showed new molecular binding structures at ARG118, ILE222, ARG224, and TYR406, and it has been proposed that sesamin could potentially be used to produce anti-H1N1 compounds. Furthermore, the mechanisms of sesamin against cytokine production from influenza type A H1N1-induced PBMCs by ELISA and signaling transduction showed that sesamin exhibits the ability to inhibit proinflammatory cytokines, IL-1β and TNF-α, and to enhance the activity of the immune cell cytokine IL-2 via downregulating the phosphorylated JNK, p38, and ERK1/2 MAPK signaling pathways. This information might very well be useful in the prevention and treatment of immune-induced inflammatory disorders.

Topics: Animals; Crystallography, X-Ray; Dioxoles; Humans; Inflammation; Influenza A Virus, H1N1 Subtype; Influenza, Human; Interleukin-1beta; Interleukin-2; Leukocytes, Mononuclear; Lignans; Models, Molecular; Molecular Dynamics Simulation; Orthomyxoviridae Infections; Signal Transduction; Swine; Swine Diseases; Tumor Necrosis Factor-alpha

Recent studies suggested that TLR4 signaling pathways played an important role in the development of LPS-induced acute lung injury (ALI). Sesamin, a sesame lignan exacted from sesame seeds, has been shown to exhibit significant anti-inflammatory activity. The purpose of this study was to investigate the anti-inflammatory effects of sesamin on LPS-induced ALI in mice. Mice ALI model was induced by intratracheal instillation of LPS. Sesamin was given 1 h after LPS challenge. Our results showed that sesamin inhibited LPS-induced lung pathological change, edema, and myeloperoxidase (MPO) activity. Sesamin suppressed LPS-induced inflammatory cytokines TNF-α, IL-6, and IL-1β production. Furthermore, sesamin inhibited LPS-induced TLR4 expression and NF-κB activation. In conclusion, the results of this study indicated that sesamin protected against LPS-induced ALI by inhibition of TLR4 signaling pathways.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Dioxoles; Edema; Enzyme Activation; Interleukin-1beta; Interleukin-6; Lignans; Lipopolysaccharides; Lung; Male; Mice; Mice, Inbred BALB C; NF-kappa B; Peroxidase; Signal Transduction; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Establishing therapeutic agents for the treatment of allergic diseases is an important focus of human health research. Sesamin, a lignan in sesame oil, exhibits a diverse range of pharmacological properties. However, to the best of our knowledge, the effect of sesamin on mast cell‑mediated allergic responses has not yet been investigated. Thus, the aim of the present study was to investigate the effect of sesamin on mast cell‑mediated allergic responses and the underlying mechanisms by which it produces this effect. In rats, oral administration of sesamin inhibited passive cutaneous anaphylaxis. Sesamin exposure attenuated immunoglobulin E‑induced histamine release from rat peritoneal mast cells, which was indicated to be mediated by the modulation of intracellular calcium. In human mast cells, sesamin reduced the stimulatory effects of phorbol 12‑myristate 13‑acetate and calcium ionophore A23187 on the production and secretion of pro‑inflammatory cytokines, including tumor necrosis factor‑α and interleukin‑6. The inhibitory effect of sesamin on pro‑inflammatory cytokine production was dependent on nuclear factor κ‑light‑chain‑enhancer of activated B cells (NF‑κB) and p38 mitogen‑activated protein kinase (MAPK). The present study demonstrates that sesamin inhibits mast cell‑derived inflammatory allergic reactions by blocking histamine release, and pro‑inflammatory cytokine production and secretion. In addition, the findings indicate that the effect of sesamin is mediated by its effect on p38 MAPK/NF‑κB signaling. Furthermore, the in vivo and in vitro anti‑allergic effects of sesamin reported in the present study suggest that it is a promising therapeutic agent for the treatment of inflammatory allergic diseases.

Topics: 2,4-Dinitrophenol; Animals; Calcium; Cell Line; Cell Survival; Cytokines; Dioxoles; Enzyme Activation; Histamine Release; Humans; Hypersensitivity; Immunoglobulin E; Inflammation Mediators; Lignans; Male; Mast Cells; Mice, Inbred ICR; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Passive Cutaneous Anaphylaxis; Peritoneum; Rats, Sprague-Dawley

A preparative separation method using consecutive sample injection centrifugal partition chromatography (CPC) was developed to obtain sesamin and sesamolin from defatted sesame meal extracts. A two-phase solvent system consisting of n-hexane-ethyl acetate-methanol-water (8:2:8:2, v/v) was applied in reversed-phase mode (descending mode). Preliminary experiments with an SCPC-100 (column volume: 100mL) were performed to select the appropriate two-phase solvent system and sample injection times; these parameters were then used with an SCPC-1000 (column volume: 1000mL) in a 10-fold scale-up preparative run. A sample containing 3g of crude extract was consecutively injected four times onto the SCPC-1000, which yielded 328mg of sesamin and 168mg of sesamolin. These compounds were analyzed by high-performance liquid chromatography and determined to have purities of 95.6% and 93.9%, respectively. Sesamin and sesamolin (30μM) increased antioxidant response element (ARE) luciferase activity 2.6-fold and 1.9-fold, respectively.

Topics: Centrifugation; Chromatography, Liquid; Dioxoles; Hep G2 Cells; Humans; Lignans; Plant Extracts; Sesamum

Intervertebral disc (IVD) degeneration contributes to most spinal degenerative diseases, while treatment inhibiting IVD degeneration is still in the experimental stage. Sesamin, a bioactive component extracted from sesame, has been reported to exert chondroprotective and anti-inflammatory effects. Here, we analyzed the anti-inflammatory and anti-catabolic effects of sesamin on rat IVD in vitro and ex vivo. Results show that sesamin significantly inhibits the lipopolysaccharide (LPS)-induced expression of catabolic enzymes (MMP-1, MMP-3, MMP-13, ADAMTS-4, ADAMTS-5) and inflammation factors (IL-1β, TNF-α, iNOS, NO, COX-2, PGE2) in a dose-dependent manner in vitro. It is also proven that migration of macrophages induced by LPS can be inhibited by treatment with sesamin. Organ culture experiments demonstrate that sesamin protects the IVD from LPS-induced depletion of the extracellular matrix ex vivo. Moreover, sesamin suppresses LPS-induced activation of the mitogen-activated protein kinase (MAPK) pathway through inhibiting phosphorylation of JNK, the common downstream signaling pathway of LPS and IL-1β, which may be the potential mechanism of the effects of sesamin. In light of our results, sesamin protects the IVD from inflammation and extracellular matrix catabolism, presenting positive prospects in the treatment of IVD degenerative diseases.

Topics: Animals; Cell Movement; Cell Survival; Cells, Cultured; Cyclooxygenase 2; Dinoprostone; Dioxoles; Enzyme Activation; Extracellular Matrix; Inflammation; Interleukin-1beta; Intervertebral Disc; Intervertebral Disc Degeneration; JNK Mitogen-Activated Protein Kinases; Lignans; Lipopolysaccharides; Macrophages; MAP Kinase Signaling System; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Nucleus Pulposus; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; RNA, Messenger; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

The study explored the protective effect of sesamin against lipid-induced renal injury and hyperlipidemia in a rat model. An animal model of hyperlipidemia was established in Sprague-Dawley rats. Fifty-five adult Sprague-Dawley rats were divided into five groups. The control group was fed a standard diet, while the other four groups were fed a high-fat diet for 5 weeks to induce hyperlipidemia. Three groups received oral sesamin in doses of 40, 80, or 160 mg/(kg·day). Seven weeks later, the blood lipids, renal function, antioxidant enzyme activities, and hyperoxide levels in kidney tissues were measured. The renal pathological changes and expression levels of collagen type IV (Col-IV) and α-smooth muscle actin (α-SMA) were analyzed. The administration of sesamin improved the serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, apolipoprotein-B, oxidized-low-density lipoprotein, and serum creatinine levels in hyperlipidemic rats, while it increased the high-density lipoprotein cholesterol and apolipoprotein-A levels. Sesamin reduced the excretion of 24-h urinary protein and urinary albumin and downregulated α-SMA and Col-IV expression. Moreover, sesamin ameliorated the superoxide dismutase activity and reduced malondialdehyde levels in kidney tissue. Sesamin could mediate lipid metabolism and ameliorate renal injury caused by lipid metabolism disorders in a rat model of hyperlipidemia.

Topics: Actins; Animals; Collagen Type IV; Diet, High-Fat; Dietary Fats; Dioxoles; Dose-Response Relationship, Drug; Dyslipidemias; Gene Expression Regulation; Kidney Diseases; Lignans; Molecular Structure; Oxidative Stress; Rats; Rats, Sprague-Dawley

Diabetic retinopathy (DR) is the common cause of diabetic vascular complications that leads to the blindness in the working age population throughout the world. Free radicals mediated oxidative stress and inflammation play a significant role in pathophysiology of DR. To find a new and safe drug to treat DR is still challenging and for that purpose the natural compounds may be therapeutic agents. Here we show that sesamin (SES), which is the main component of sesame seed and its oil, and has been reported as potent antioxidant and neuroprotective, could be a therapeutic agent in DR. In the present study, we investigated protective effect of SES in Streptozotocin (STZ) induced DR in mice. The mice were divided into three groups (Control, DR and DR+SES) for the study. After two weeks post-diabetic establishment, mice were treated with SES (30mg/kg BW, i.p, alternate day) for four weeks. Mice body weight and blood glucose level were measured from each group. The microglial activation of retina was determined by immunohistochemistry analysis by using Iba-1 as a microglia marker. Retinal mRNA levels of Iba-1, tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS) and Intercellular Adhesion Molecule 1 (ICAM-1) were examined by qRT-PCR. The level of iNOS protein expression was examined by immunoblotting. Together these data demonstrate that SES treatment lowered the progression of diabetic retinal injury by: 1) decreasing blood glucose level, 2) suppressing microglia activation, 3) reducing retinal TNF-α and ICAM-1 levels and 4) quenching iNOS expression. In conclusion, the results suggest that SES treatment may be of therapeutic benefit in reducing the progression of DR by ameliorating hyperglycemia and inflammation in diabetic retina.

Topics: Analysis of Variance; Animals; Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Blood Glucose; Body Weight; Calcium-Binding Proteins; Diabetic Retinopathy; Dioxoles; Disease Models, Animal; Intercellular Adhesion Molecule-1; Lignans; Mice; Microfilament Proteins; Microglia; Nitric Oxide Synthase Type II; Retina; RNA, Messenger; Streptozocin; Tumor Necrosis Factor-alpha; Up-Regulation

Furofuran lignans such as sesamin have been recognized as promising antidiabetic agents as they possess curative as well as preventive effects toward diabetes complications. However, to date the structure-activity relationship has not been investigated due to the lack of a practical synthetic route capable of producing diverse furofuran lignans. Herein, we first introduced a single-step synthesis of these compounds starting from samin (4). Reaction of samin with a variety of electron-rich phenolics under acidic conditions afforded a total of 23 diverse furofuran lignans. On examination their inhibitions against α-glucosidase and free radicals, lignans having a free hydroxy group showed considerably enhanced inhibition, compared with their corresponding starter 4 and related lignans sesamin (1) and sesamolin (3). In addition, the mechanism underlying the α-glucosidase inhibition of a particular active lignan (epi -6) was verified to be mixed manner between competitive and noncompetitive inhibition.

Topics: alpha-Glucosidases; Animals; Dioxoles; Free Radicals; Glycoside Hydrolase Inhibitors; Hypoglycemic Agents; Lignans; Rats

Rheumatoid arthritis (RA) is an autoimmune disease associated with chronic inflammatory arthritis. TNF-α and OSM are pro-inflammatory cytokines that play a key role in RA progression. Thus, reducing the effects of both cytokines is practical in order to relieve the progression of the disease. This current study is interested in sesamin, an active compound in sesame seeds. Sesamin has been shown to be a chondroprotective agent in osteoarthritis models. Here, we have evaluated a porcine cartilage explant as a cartilage degradation model related to RA induced by TNF-α and/or OSM in order to investigate the effects of sesamin on TNF-α and OSM in the cartilage degradation model.. A porcine cartilage explant was induced with a combination of TNF-α and OSM (test group) or IL-1β and OSM (control group) followed by a co-treatment of sesamin over a long-term period (35 days). After which, the tested explants were analyzed for indications of both the remaining and the degradation aspects using glycosaminoglycan and collagen as an indicator.. The combination of TNF-α and OSM promoted cartilage degradation more than either TNF-α or OSM alone and was comparable with the combination of IL-1β and OSM. Sesamin could be offering protection against cartilage degradation by reducing GAGs and collagen turnover in the generated model.. Sesamin might be a promising agent as an alternative treatment for RA patients. Furthermore, the generated model revealed itself to be an impressive test model for the analysis of phytochemical substances against the cartilage degradation model for RA. The model could be used to test for the prevention of cartilage degradation in other biological agents induced with TNF-α and OSM as well.

Topics: Animals; Arthritis, Rheumatoid; Cartilage; Dioxoles; Immunohistochemistry; Lignans; Models, Biological; Oncostatin M; Protective Agents; Swine; Tumor Necrosis Factor-alpha

Sesamin is one of the major lignans found in sesame oil. Although some microbial metabolites of sesamin have been identified, sesamin-metabolic pathways remain uncharacterized at both the enzyme and gene levels. Here, we isolated microorganisms growing on sesamin as a sole-carbon source. One microorganism showing significant sesamin-degrading activity was identified as Sinomonas sp. no. 22. A sesamin-metabolizing enzyme named SesA was purified from this strain and characterized. SesA catalyzed methylene group transfer from sesamin or sesamin monocatechol to tetrahydrofolate (THF) with ring cleavage, yielding sesamin mono- or di-catechol and 5,10-methylenetetrahydrofolate. The kinetic parameters of SesA were determined to be as follows: Km for sesamin = 0.032 ± 0.005 mM, Vmax = 9.3 ± 0.4 (μmol⋅min(-1)⋅mg(-1)), and kcat = 7.9 ± 0.3 s(-1) Next, we investigated the substrate specificity. SesA also showed enzymatic activity toward (+)-episesamin, (-)-asarinin, sesaminol, (+)-sesamolin, and piperine. Growth studies with strain no. 22, and Western blot analysis revealed that SesA formation is inducible by sesamin. The deduced amino acid sequence of sesA exhibited weak overall sequence similarity to that of the protein family of glycine cleavage T-proteins (GcvTs), which catalyze glycine degradation in most bacteria, archaea, and all eukaryotes. Only SesA catalyzes C1 transfer to THF with ring cleavage reaction among GcvT family proteins. Moreover, SesA homolog genes are found in both Gram-positive and Gram-negative bacteria. Our findings provide new insights into microbial sesamin metabolism and the function of GcvT family proteins.

Topics: Dioxoles; Kinetics; Lignans; Micrococcaceae; Mutation; Soil Microbiology; Substrate Specificity

Topics: Chromatography, Reverse-Phase; Countercurrent Distribution; Dioxoles; Lignans; Sesame Oil; Sesamum; Tandem Mass Spectrometry

Nonalcoholic fatty liver disease (NAFLD) is defined by a nonalcohol relevant pathological accumulation of fat in the liver. Previous studies have shown that sesamin exerts antioxidant effects and improves lipid metabolism of the fatty liver. In this study, we hypothesized that sesamin improves lipid homeostasis of Sprague-Dawley rats fed a high-fat diet (HFD) by regulating the expression of genes related to de novo lipogenesis and β-oxidation. We induced NAFLD in rats with HFD and examined the effect of sesamin in vivo. The results showed that HFD rats accumulated total cholesterol and triacylglycerols in the liver and developed inflammation, as evidenced by the elevation of interleukin-6 and tumor necrosis factor-α in the liver and serum. Sesamin attenuated the disease progression by improving the blood lipid profile in a dose-dependent manner. Sesamin reduced the serum levels of total cholesterol, triacylglycerols, low-density lipoprotein cholesterol, and free fatty acid, whereas it increased the level of high-density lipoprotein cholesterol. Meanwhile, sesamin increased the activities of hepatic glutathione peroxidase and superoxide dismutase while reducing the level of malonaldehyde and cytochrome P450 2E1. Furthermore, higher doses of sesamin reduced the expression of liver X receptor α and its downstream target genes, whereas it upregulated the peroxisome proliferator-activated receptor α-mediated signaling. These findings suggest that sesamin attenuates diet-induced dyslipidemia and inflammation of NAFLD in rats via mechanisms regulated by liver X receptor α and peroxisome proliferator-activated receptor α.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cytochrome P-450 CYP2E1; Diet, High-Fat; Dioxoles; Dyslipidemias; Hypolipidemic Agents; Inflammation; Interleukin-6; Lignans; Lipid Metabolism; Lipids; Lipogenesis; Liver; Liver X Receptors; Male; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Phytotherapy; Plant Extracts; PPAR alpha; Rats, Sprague-Dawley; Sesamum; Tumor Necrosis Factor-alpha

This study investigated the effects of (-)-sesamin on memory deficits induced by chronic electric footshock (EF)-induced stress in mice. Mice were treated with (-)-sesamin (25 and 50mg/kg, p.o., daily for 21day) prior to chronic EF stress (0.6mA, 1s every 5s for 3min, daily for 21day). Transfer retention latencies in the elevated plus maze test and N-methyl-d-aspartate (NMDA) receptor (type 1) phosphorylation in the hippocampus increased with chronic EF stress, and they were reduced by treatment with (-)-sesamin at both doses. Phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cyclic AMP-responsive element binding protein (CREB), which were reduced by chronic EF stress, were increased by treatment with (-)-sesamin. Retention latencies in the passive avoidance test and dopamine levels in the substantia nigra-striatum were also reduced by chronic EF stress, and similarly recovered with (-)-sesamin treatment. These results suggest that (-)-sesamin ameliorates the effects of chronic EF stress-induced spatial and habit learning memory deficits by modulating both NMDA receptor and dopaminergic neuronal systems.

Topics: Animals; Avoidance Learning; Corpus Striatum; Cyclic AMP Response Element-Binding Protein; Dioxoles; Dopamine; Electroshock; Hippocampus; Lignans; Male; Maze Learning; Memory Disorders; Mice, Inbred ICR; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Phosphorylation; Reaction Time; Receptors, N-Methyl-D-Aspartate; Spatial Memory; Stereoisomerism; Stress, Physiological

The present study investigated the effects of (-)-sesamin on motor and memory deficits in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model of Parkinson's disease (PD) with l-3,4-dihydroxyphenylalanine (l-DOPA). MPTP-lesioned (30mg/kg/day, 5days) mice showed deficits in memory including habit learning memory and spatial memory, which were further aggravated by daily treatment with 25mg/kg l-DOPA for 21days. However, daily treatment with (-)-sesamin (25 and 50mg/kg) for 21days ameliorated memory deficits in an MPTP-lesioned mouse model of PD treated with l-DOPA (25mg/kg). Both (-)-sesamin doses reduced decreases in the retention latency time in the passive avoidance test, latency to fall of rotarod test and distance traveled in the open field test, and attenuated decreases in tyrosine hydroxylase (TH)-immunopositive cells, dopamine, and its metabolites in the substantia nigra-striatum. (-)-Sesamin reduced increases in the retention transfer latency time in the elevated plus-maze test and N-methyl-d-aspartate receptor (NMDAR) expression and reduced decreases in the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cyclic AMP-response element binding protein (CREB) in the hippocampus. In contrast, daily treatment with 10mg/kg l-DOPA for 21days ameliorated memory deficits in MPTP-lesioned mice, and this effect was further improved by treatment with (-)-sesamin (25 and 50mg/kg). These results suggest that (-)-sesamin protects against habit learning memory deficits by activating the dopamine neuronal system, while spatial memory deficits are decreased by its modulatory effects on the NMDAR-ERK1/2-CREB system. Accordingly, (-)-sesamin may act as an adjuvant phytonutrient for motor and memory deficits in patients with PD receiving l-DOPA.

Topics: Animals; Antiparkinson Agents; Avoidance Learning; Corpus Striatum; Dioxoles; Dopamine; Dose-Response Relationship, Drug; Levodopa; Lignans; Male; Memory; Memory Disorders; Mice, Inbred C57BL; Motor Activity; Nootropic Agents; Parkinsonian Disorders; RNA, Messenger; Substantia Nigra

Sesamin, a bioactive component extracted from sesame, has been reported to exert anti-inflammatory and anti-oxidant effects. In this study, we evaluated the anti-inflammatory effects of sesamin on IL-1β-stimulated human osteoarthritis chondrocytes and investigated the possible mechanism. Results demonstrated that sesamin treatment significantly inhibited PGE2 and NO production induced by IL-1β. Sesamin inhibited MMP1, MMP3, and MMP13 production in IL-1β-stimulated chondrocytes. Sesamin also inhibited IL-1β-induced phosphorylation of NF-κB p65 and IκBα. Meanwhile, sesamin was found to up-regulate the expression of Nrf2 and HO-1. However, Nrf2 siRNA reversed the anti-inflammatory effects of sesamin. In conclusion, our results suggested that sesamin showed anti-inflammatory effects in IL-1β-stimulated chondrocytes by activating Nrf2 signaling pathway.

Topics: Anti-Inflammatory Agents; Cell Survival; Cells, Cultured; Chondrocytes; Dinoprostone; Dioxoles; Dose-Response Relationship, Drug; Heme Oxygenase-1; Humans; Interleukin-1beta; Lignans; Matrix Metalloproteinases, Secreted; Middle Aged; NF-E2-Related Factor 2; NF-KappaB Inhibitor alpha; Nitric Oxide; Osteoarthritis, Knee; Phosphorylation; RNA Interference; Signal Transduction; Transcription Factor RelA; Transfection

Amyloid beta-protein (Aβ) is involved in the pathogenesis of Alzheimer's disease (AD). Aβ induces free radical production in neuronal cells, leading to oxidative stress and up-regulation of c-Jun N-terminal kinases (JNK), extracellular-signal-regulated kinases (ERK), p38 mitogen-activated protein kinase (MAPK) pathways and pro-apoptotic Bax expression. Sesamin has been shown to have protection to several models of neurodegenerative diseases by its antioxidant and anti-inflammatory properties. In the present study, we examined the neuroprotective effect of a sesamin derivative, 3-bis (3-methoxybenzyl) butane-1,4-diol (BBD) on Aβ1-42 induced cytotoxicity of PC12 cells. Aβ1-42 induced lipid peroxidation, calcium, reactive oxygen species from the PC12 cells. The effect of BBD on these harmful factors and the related signaling pathways were examined by biochemical and western blot assays. The result showed that BBD protected PC12 cells from Aβ1-42 induced cytotoxicity with the increased cell viability and acetylcholine release, and the decreased lactate dehydrogenase, malondialdehyde and calcium release. BBD significantly reduced Aβ-induced JNK, ERK, p38 MAPK pathways and Bax expression in PC12 cells. Therefore the neuroprotective effect of BBD on Aβ-induced cytotoxicity was involved with antioxidant and anti-inflammatory effects. The result would help the development of new CNS drug for protection of AD.

Topics: Amyloid beta-Peptides; Animals; Butylene Glycols; Cell Survival; Dioxoles; Lignans; MAP Kinase Signaling System; Neuroprotective Agents; PC12 Cells; Peptide Fragments; Rats

Activation of vascular smooth muscle cells (VSMC), a key event in the pathogenesis of atherosclerosis, is triggered by inflammatory stimuli such as tumour necrosis factor-alpha (TNF-α) causing a mitogenic VSMC response. The polyphenol (+)-episesamin (ES) was shown to counteract TNF-α-induced effects, for example in macrophages. Aiming for novel therapeutic options, we here investigated whether ES protects VSMC from TNF-α-induced growth and migration, which both contribute to the onset and progression of atherosclerosis.. Human and murine VSMC were treated with combinations of ES and TNF-α. Expressions of mRNA were analyzed by RT-PCR. Enzymatic activities and proliferation were determined by specific substrate assays. Cell signalling was analyzed by Western blot and reporter gene assays. Migration was assessed by wound healing assays.. ES at 1-10 μm reduced basal and TNF-α-induced VSMC proliferation and migration due to impaired activation of extracellular signal-regulated kinases (ERK)1/2, Akt (protein kinase B), nuclear factor-kappa B (NF-ĸB) and vascular cell adhesion molecule (VCAM)-1. This was accompanied by reduced expression and secretion of matrix metalloproteinases (MMP)-2/-9, which are known to promote VSMC migration. Specific inhibitors of Akt, NF-ĸB and MMP-2/-9 reduced TNF-α-induced VSMC proliferation, confirming ES-specific effects. Besides, ES reduced TNF-α- and H₂O₂ -induced oxidative stress and in parallel induces anti-inflammatory haem oxygenase (HO)-1 expression.. ES interferes with inflammation-associated VSMC activation and subsequent decreased proliferation and migration due to anti-oxidative properties and impaired activation of NF-ĸB, known contributors to atherogenesis. These results suggest ES as a complemental treatment of VSMC specific vascular diseases such as atherosclerosis.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cell Line; Cell Movement; Cell Proliferation; Dioxoles; Dose-Response Relationship, Drug; Enzyme Activation; Gelatinases; Humans; Lignans; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; NF-kappa B; Oxidative Stress; Proto-Oncogene Proteins c-akt; RNA, Messenger; Signal Transduction; Tumor Necrosis Factor-alpha

Diverse risk factors for diabetes can induce oxidative stress, leading to pancreatic beta cell damage and insulin secretion dysfunction. In the present study, we evaluated the effect of sesamin on streptozotocin (STZ) induced apoptosis in INS-1 cells and the possible mechanisms implicated. After preincubation with indicated concentrations of sesamin (0.1, 1.0 and 10.0μmol/l) for 24h, INS-1 cells were exposed to STZ (3mmol/l) for 12h. Sesamin effectively improved STZ induced cell damage as determined by MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide] assay and insulin secretion capacity, and suppressed STZ induced cell apoptosis as evaluated by flow cytometry using annexin V and propidium iodide double staining. Western blot analysis demonstrated that sesamin markedly suppressed STZ induced nuclear factor kappa B (NF-κB) activation, with Bax protein down-regulated and Bcl-2 protein up-regulated significantly. Preincubation with sesamin resulted in an evident enhancement of total antioxidant capacity in INS-1 cells, accompanied by a significant reduction of intracellular reactive oxygen species and malondialdehyde, an end product of lipid peroxidation. Taken together, these findings suggested that sesamin was capable of suppressing STZ induced INS-1 cell apoptosis, which might be ascribed, at least partly, to the inhibition of NF-κB activation and subsequent regulation of Bcl-2 family protein expression. This study would provide a potential target for treatment of diabetes with sesamin as well as other antioxidants.

Topics: Animals; Antioxidants; Apoptosis; bcl-2-Associated X Protein; Cell Line; Cell Survival; Dioxoles; Gene Expression Regulation; Insulin; Insulin Secretion; Insulin-Secreting Cells; Intracellular Space; Lignans; Malondialdehyde; NF-kappa B; Oxidative Stress; Proto-Oncogene Proteins c-bcl-2; Rats; Reactive Oxygen Species; Signal Transduction; Streptozocin

1. This study examined hepatic cytochrome P450 (CYP450) response to dietary sesamin in combination with different n-6/n-3 fatty acid ratios in fish diet. Over a period of 4 months, fish were fed seven different experimental diets an n-6/n-3 FA ratio of either 0.5 or 1.0 in combination with two sesamin levels: low sesamin = 1.16 g/kg feed and high sesamin = 5.8 g/kg feed. Control diets did not contain sesamin. 2. The CYP450-associated activities of ethoxyresorufin O-deethylase (EROD), 7-benzyloxy-4-trifluoromethylcoumarin O-debenzylation (BFCOD), pentoxyresorufin O-depentylase (PROD), coumarin hydroxylase (COH), methoxyresorufin O-deethylase (MROD) and p-nitrophenol hydroxylase (PNPH) were significantly induced by dietary sesamin in a dose-related manner. 3. Expressions of the genes CYP1A1, CYP1A3, CYP3A, AhR1α, AhR2β, AhR2δ and PXR involved in the regulation of CYP450 activities, was not the primary source of this induction.

Topics: Animals; Cytochrome P-450 Enzyme System; Dioxoles; Fish Oils; Gene Expression Regulation; Lignans; Liver; Plant Oils; Salmo salar; Xenobiotics

Sesame seed is rich in sesamin. The present study was to (i) investigate the plasma cholesterol-lowering activity of dietary sesamin and (ii) examine the interaction of dietary sesamin with the gene expression of sterol transporters, enzymes, receptors, and proteins involved in cholesterol metabolism. Thirty hamsters were divided into three groups fed the control diet (CON) or one of two experimental diets containing 0.2% (SL) and 0.5% (SH) sesamin, respectively, for 6 weeks. Plasma total cholesterol (TC) levels in hamsters given the CON, SL, and SH diets were 6.62 ± 0.40, 5.32 ± 0.40, and 5.00 ± 0.44 mmol/L, respectively, indicating dietary sesamin could reduce plasma TC in a dose-dependent manner. Similarly, the excretion of total fecal neutral sterols was dose-dependently increased with the amounts of sesamin in diets (CON, 2.65 ± 0.57; SL, 4.30 ± 0.65; and SH, 5.84 ± 1.27 μmol/day). Addition of sesamin into diets was associated with down-regulation of mRNA of intestinal Niemann-Pick C1 like 1 protein (NPC1L1), acyl-CoA:cholesterol acyltransferase 2 (ACAT2), microsomal triacylglycerol transport protein (MTP), and ATP-binding cassette transporters subfamily G members 5 and 8 (ABCG5 and ABCG8). Results also showed that dietary sesamin could up-regulate hepatic cholesterol-7α-hydroxylase (CYP7A1), whereas it down-regulated hepatic 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase and liver X receptor alpha (LXRα). It was concluded that the cholesterol-lowering activity of sesamin was mediated by promoting the fecal excretion of sterols and modulating the genes involved in cholesterol absorption and metabolism.

Topics: Animals; Anticholesteremic Agents; ATP-Binding Cassette Transporters; Biological Transport; Carrier Proteins; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Cricetinae; Dioxoles; Down-Regulation; Humans; Hypercholesterolemia; Intestinal Mucosa; Intestines; Lignans; Liver X Receptors; Male; Mesocricetus; Orphan Nuclear Receptors; Sterol O-Acyltransferase; Sterol O-Acyltransferase 2

We compared the physiological activities of sesame seeds rich in lignans from three varieties (Gomazou, Maruhime and Maruemon), and those from a conventional cultivar (Masekin) in rats. The sum of the values of fat-soluble lignans (sesamin and sesamolin) in seeds of Gomazou, Maruhime and Maruemon varieties was approximately double the value in Masekin. Seeds from Maruemon contained fat-soluble lignan most exclusively as sesamin while other varieties contained sesamin and sesamolin at about a 2:1 ratio. After a 16 d experiment, sesame seeds, added at 200 g/kg to the experimental diets, increased the activity and mRNA levels of fatty acid oxidation enzymes. Increases were stronger with seeds rich in lignans than with seeds from Masekin. In contrast, sesame seeds lowered the activity and mRNA levels of lipogenic enzymes. However, sesame seeds from all the varieties were comparable in affecting these parameters. Serum triacylglycerol concentrations were lower in rats fed diets containing sesame seeds rich in lignans than in those fed a diet free of sesame seeds or a diet containing seeds from the Masekin variety. Serum malondialdehyde (a marker of lipid peroxidation) was lower in rats fed diets containing sesame seeds rich in lignans than in those fed a sesame seed-free diet or Masekin diet. It is apparent that sesame seeds rich in lignans, irrespective of lignan composition, more profoundly affect hepatic fatty acid oxidation and serum triacylglycerol levels and possibly attenuate oxidative stress. Therefore, consumption of sesame seeds rich in lignans hopefully results in physiological activity to promote health.

Topics: Animals; Dioxoles; Fatty Acids; Lignans; Lipogenesis; Liver; Male; Malondialdehyde; Oxidation-Reduction; Oxidative Stress; Rats, Sprague-Dawley; Seeds; Sesamum; Solubility; Triglycerides

Sesamin and sesamolin are the major oil-soluble lignans present in sesame seed, having a wide range of biological functions beneficial to human health. Understanding sesame domestication history using sesamin synthase gene expression could enable delineation of the sesame putative progenitor. This report examined the functional expression of sesamin synthase (CYP81Q1) during capsule maturation (0-40 days after flowering) in three wild Sesamum species and four sesame cultivars. Among the cultivated accessions, only S. indicum (CO-1) exhibited transcript abundance of sesamin synthase along with high sesamin content similar to S. malabaricum, while the other cultivated sesame showed low expression. The sesamin synthase expression analysis, coupled with quantification of sesamin level, indicates that sesamin synthase was not positively favoured during domestication. The sesamin synthase expression pattern and lignan content, along with phylogenetic analysis suggested a close relationship of cultivated sesame and the wild species S. malabaricum. The high genetic identity between the two species S. indicum and S. malabaricum points towards the role of the putative progenitor S. malabaricum in sesame breeding programmes to broaden the genetic base of sesame cultivars. This study emphasises the need to investigate intraspecific and interspecific variation in the primary, secondary and tertiary gene pools to develop superior sesame genotypes.

Topics: Base Sequence; Biosynthetic Pathways; Dioxoles; Gene Expression; Genotype; Lignans; Molecular Sequence Data; Phylogeny; Seeds; Sequence Analysis, DNA; Sesamum; Species Specificity

The objective of this study was to study the mechanism of the anti-rejection effect of Asarinin in rats that underwent cardiac allograft implantation.. Hearts from Wistar rats were transplanted into the abdominal cavity of Sprague Dawley rats (SD rats) 64 SD rats received either cyclosporin A (CsA), Asarinin, or demi-dose of cyclosporine A and Asarinin through oral administration. On the seventh day post-transplantation, the expression of Toll-like receptor 4 (TLR4), chemokine (C-X-C motif) receptor 3 (CXCR3) in myocardium, and the level of interleukin (IL)-12 in the peripheral blood were analyzed 7 days after transplantation.. The survival time in 3 groups (CsA group, Asarinin group, and semi-dose CsA group) prolonged (P < .01), the microscope myocardial histopathology in 3 groups (CsA group, Asarinin group and semi-dose CsA group) relieved, the expression of TLR4 and CXCR3 in 3 groups was significantly decreased (P < .01) when compared with the control group. The level of IL-12 decreased remarkably (P < .05) in the 3 groups when compared with the control group.. The combined data suggested that Asarinin decreased peripheral blood concentration of IL-12 and inhibited the expression of TLR4 and CXCR3, which means Asarinin may have a role on TLR4 pathway and produced prolongation of allograft heart survival.

Topics: Allografts; Animals; Antioxidants; Cyclosporine; Dioxoles; Graft Rejection; Graft Survival; Heart Transplantation; Immunosuppressive Agents; Interleukin-12; Lignans; Male; Models, Animal; Myocardium; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptors, CXCR3; Toll-Like Receptor 4; Transplantation, Homologous

This study investigated the effect of sesamin on myocardial fibrosis in spontaneously hypertensive rats (SHRs) and the possible mechanisms involved. Twenty-eight male SHRs were randomly allocated to SHR group, Ses160 group (sesamin 160 mg/kg), Ses80 group (sesamin 80 mg/kg) and Cap30 group (captopril 30 mg/kg). Seven male WKY rats were used as control. Sesamin and captopril were administered intragastrically for 12 weeks. Captopril significantly reduced systolic blood pressure and angiotensin II (Ang II) levels in SHRs, accompanied by a marked attenuation of left ventricular hypertrophy (LVH) and collagen deposition (P <0.05 or P <0.01). Though sesamin had no significant influence on Ang II levels, and the hypotensive effect was also significantly inferior to that of captopril (P <0.05 or P <0.01), however, the improvement of LVH and collagen deposition was similar to that in captopril group. Sesamin markedly reduced transforming growth factor-β1 (TGF-β1) content in cardiac tissues, with Smad3 phosphorylation decreased and Smad7 protein expression increased notably (P <0.05 or P <0.01). Protein expression of type I collagen and type III collagen, target genes of Smad3, was down-regulated markedly by sesamin (P <0.05 or P <0.01). In addition, sesamin significantly increased total antioxidant capacity and superoxide dismutase protein in cardiac tissues (P <0.05 or P <0.01), while the expression of NADPH oxidase subunit p47phox and malondialdehyde content were reduced markedly (P <0.05 or P <0.01). In vitro studies also demonstrated that sesamin was able to suppress Ang II induced phosphorylation of Smad3 and secretion of TGF-β1 and type I and type III collagen in cultured rat cardiac fibroblasts. These data suggest that sesamin is capable of attenuating hypertensive myocardial fibrosis through, at least partly, suppression of TGF-β1/Smad signaling pathway.

Topics: Angiotensin II; Animals; Antioxidants; Blood Pressure; Collagen Type I; Collagen Type III; Dioxoles; Fibroblasts; Fibrosis; Heart Ventricles; Lignans; Male; Malondialdehyde; Myocardium; NADPH Oxidases; Organ Size; Phosphorylation; Rats, Inbred SHR; Signal Transduction; Smad3 Protein; Smad7 Protein; Superoxide Dismutase; Systole; Transforming Growth Factor beta1

Sesamin, a lipid-soluble lignan, is one of the major constituents of sesame. Previous studies have reported that sesamin induces growth inhibition in human cancer cells, particularly prostate cancer cells. In the present study, we mainly explored the mechanism underlying the protective effect of sesamin on prostate cancer cell proliferation and invasion induced by lipopolysaccharide (LPS). We found that the proliferation of PC3 cells, as determined using the MTT assay, and the expression of cyclin D1, COX-2, Bcl-2 and survivin proteins elevated by LPS were distinctly inhibited by sesamin in a dose-dependent manner. Meanwhile, the ability of PC3 cell invasion, as determined using the Transwell assay and the expression of matrix metalloproteinase 9 (MMP-9), intercellular adhesion molecule-1 (ICAM-1) and vascular endothelial growth factor (VEGF) proteins increased by LPS were obviously reduced by sesamin in a dose-dependent manner. In addition, the accumulation of TGF-α and interleukin-6 (IL-6) production induced by LPS in the culture supernatant was found to be decreased dose-dependently with sesamin pretreatment in PC3 cells using the enzyme-linked immunosorbent assay (ELISA) kit. Furthermore, phosphorylation of the p38 protein and nuclear factor (NF)-κB activity in the PC3 cells were enhanced by LPS and further inhibited with sesamin, SB203580 pretreatment or p38-siRNA transfection, respectively. Sesamin or SB203580 pretreatment obviously inhibited PC3 cells-derived tumor growth induced by LPS in vivo. Taken together, these results suggest that the potential ability of sesamin to downregulate the secretion of cytokines and the expression of cell proliferative- and invasive-related gene products induced by LPS was shown to be via the p38 mitogen-activated protein kinase (p38-MAPK) and NF-κB signaling pathways, which may be one of the mechanisms of the anticancer activity of this sesamin agent in prostate cancer cells.

Topics: Cell Line, Tumor; Cell Proliferation; Cytokines; Dioxoles; Gene Expression Regulation, Neoplastic; Humans; Imidazoles; Lignans; Lipopolysaccharides; Male; Neoplasm Invasiveness; Neoplasm Proteins; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Prostatic Neoplasms; Pyridines; Signal Transduction

Sesamin has been described to exert anti-oxidant and anti-inflammatory properties. In present study, we investigated the potential effects and mechanisms of sesamin on lipopolysaccharide (LPS)-induced fulminant hepatic failure (FHF) in d-galactosamine (D-GalN)-sensitized mice. Our results showed that pretreatment with sesamin dose-dependently improved LPS/D-GalN-induced mortality and liver injury as indicated by reduced serum levels of aminotransferases and alleviated pathological damage as well as hepatocyte apoptosis in mice. Additionally, sesamin markedly attenuated LPS/D-GalN-induced adhesion molecules expression, and decreased neutrophils recruitment. Furthermore, sesamin inhibited LPS-induced tumor necrosis factor-alpha (TNF-α) production, p38 mitogen-activated protein kinases (MAPK) and NF-κB activation, and Toll like receptor (TLR) 4 expression in mice and in RAW264.7 macrophage cells. In summary, these results demonstrate that sesamin protects mice from LPS-induced FHF and the molecular mechanisms may down-regulate the expression of TLR4, block MAPK and NF-κB activation, decrease the production of TNF-α.

Topics: Animals; Antioxidants; Cell Line; Dioxoles; Galactosamine; Lignans; Lipopolysaccharides; Liver; Liver Failure, Acute; Male; Mice; Mice, Inbred BALB C; Protective Agents; Signal Transduction; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

There is considerable interest in dietary lignans since they have been shown to have antioxidant, estrogenic and lipid-lowering activity in humans. In this study, the fluorescent excitation and emission spectra of seven lignans were characterized and their relative fluorescent intensities compared. The lignans were found to have similar excitation (286.6 ± 2.5 nm, X ± SD) and emission (320.1 ± 6.4 nm) maxima; however, their fluorescence intensities on a molar basis decreased in the following order: asarinin, sesamin, sesamolin, seco-isolariciresinol, seco-isolariciresinol diglucoside and matairesinol. Enterolactone, a mammalian lignan conversion product, and sesamol, an antioxidant found in sesame oil, also exhibited significant fluorescence excitation and emission intensities. A high-performance liquid chromatographic method using photodiode array (PDA) and fluorescent detection was developed for the analysis of the individual lignans. Analysis was performed on a reversed phase C-18 column with methanol-water (70:30, v/v) as the mobile phase. With fluorescent detection, the limits of quantitation (LOQ) was 0.1 ng or 2.82 nmol for sesamin and asarinin, 2.70 nmol for sesamolin, 2.76 nmol for seco-isolariciresinol, 1.45 nmol for seco-isolariciresinol diglucoside, 2.79 nmol for matairesinol and 0.5 ng or 1.67 nmol for enterolactone. With PDA detection, the LOQ was a 1000-fold less sensitive than with fluorescent detection.

Topics: Benzodioxoles; Chromatography, High Pressure Liquid; Dioxoles; Lignans; Phenols; Sensitivity and Specificity; Spectrometry, Fluorescence

The plant growth regulatory activity of furofuran lignan (7,9':7',9-diepoxylignan) was evaluated by employing optically pure synthesized (+)- and (-)-enantiomers. (+)-Sesamin possessing a 3,4-methylenedioxy group on the aromatic rings and 7-aryl structure showed growth promotion activity against lettuce roots (EC50 = 0.50 mM); on the other hand, growth inhibitory activity was observed against lettuce shoots (EC50 = 0.38 mM). Against ryegrass shoots, (-)-sesamolin, which has 3,4-methylenedioxy groups on the aromatic rings and a 7-acetal structure, was effective in showing growth inhibitory activity (EC50 = 0.23 mM). Different activity levels were observed between (+)- and (-)-enantiomers. It was assumed that the 3,4-methylenedioxy group on the aromatic ring was more potent for the plant growth regulatory activity.

Topics: Dioxoles; Lactuca; Lignans; Lolium; Molecular Structure; Plant Growth Regulators; Plant Roots; Plant Shoots; Stereoisomerism

Dietary prevention has been known to reduce breast cancer risk. Sesamin is one of the major components in sesame seeds and has been widely studied and proven to have anti-proliferation and anti-angiogenic effects on cancer cells. In this study, the influence of sesamin was tested in the human breast cancer MCF-7 cell line for cell viability (MTT assay) and cell cycling (flow cytometry). Results showed that sesamin dose-dependently (1, 10 and 50 μM) reduced the cell viability and increased LDH release and apoptosis (TUNEL assay). In addition, there was a significant increase of sub-G1 phase arrest in the cell cycle after sesamin treatment. Furthermore, sesamin increased the expression of apoptotic markers of Bax, caspase-3, and cell cycle control proteins, p53 and checkpoint kinase 2. Taken together, these results suggested that sesamin might be used as a dietary supplement for prevention of breast cancer by modulating apoptotic signal pathways and inhibiting tumor cell growth.

Topics: Antioxidants; Apoptosis; Blotting, Western; Breast Neoplasms; Cell Cycle Checkpoints; Cell Proliferation; Checkpoint Kinase 2; Dioxoles; Female; Humans; Lignans; Tumor Cells, Cultured

The blood pressure lowering effect of sesamin has been demonstrated to be associated with the increase in vascular nitric oxide (NO) biological activity by our previous studies and others. The present study was designed to explore the underlying mechanisms involved in the effect of sesamin on aortic NO bioactivity in spontaneously hypertensive rats (SHRs).. Sesamin was orally administered for 8 consecutive weeks in SHRs. Systolic blood pressure (SBP) was measured using the tail-cuff method. The aortas were isolated and in vitro vascular reactivity studies were performed. Superoxide anion production in carotid arteries was assessed by dihydroethidium fluorescence staining. The protein expression of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (P-eNOS), dihydrofolate reductase (DHFR), nicotinamide adenine dinucleotide phosphate oxidase subunit p47phox, and copper, zinc superoxide dismutase (Cu/Zn-SOD) in aortas was detected by Western blotting. The dimeric form of eNOS in aortas was determined by low-temperature sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Aortic level of nitrotyrosine and activities of antioxidant enzymes, namely, total SOD (T-SOD), glutathione peroxidase (GPx) and catalase were also detected.. In SHRs, sesamin treatment reduced SBP, improved vascular relaxation induced by acetylcholine and enhanced aortic NO bioactivity. Sesamin treatment enhanced NO biosynthesis in SHR aortas was due to upregulated P-eNOS and suppressed eNOS uncoupling, and the latter effect might be attributed to decreased nitrotyrosine and upregulated DHFR. Sesamin also reduced the NO oxidative inactivation and decreased the superoxide anion production through downregulation of p47(phox) and amelioration of eNOS uncoupling. In addition, sesamin treatment did not alter the levels of GPx and catalase activity but obviously reduced the compensatory elevated T-SOD activity and Cu/Zn-SOD protein expression.. Chronic treatment with sesamin could reduce hypertension and improve endothelial dysfunction through enhancement of NO bioactivity in SHR aortas.

Topics: Animals; Antihypertensive Agents; Antioxidants; Aorta; Blood Pressure; Blotting, Western; Dioxoles; Down-Regulation; Electrophoresis, Polyacrylamide Gel; Endothelium, Vascular; Hypertension; Lignans; Male; Nitric Oxide; Nitric Oxide Synthase Type III; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Superoxide Dismutase; Up-Regulation

Advanced glycation end products (AGEs), the direct modulators of β-cells, have been shown to cause insulin-producing β-cell dysfunction and apoptosis through increase of intracellular reactive oxygen species (ROS) production. Sesamin has been demonstrated to possess antioxidative activity. This study was designed to investigate whether sesamin protects against AGEs-evoked β-cell damage via its antioxidant property. The effects of sesamin were examined in C57BL/6J mice and MIN6 cell line. In in vivo studies, mice were intraperitoneally injected with AGEs (120 mg/kg) and orally treated with sesamin (160 mg/kg) for four weeks. Intraperitoneal glucose tolerance and insulin releasing tests were performed. Insulin content, ROS generation and β-cell apoptosis in pancreatic islets were also measured. In in vitro studies, MIN6 cells were pretreated with sesamin (50 or 100 μM) and then exposed to AGEs (200 mg/L) for 24 h. Insulin secretion, β-cell death, ROS production as well as expression and activity of NADPH oxidase were determined. Sesamin treatment obviously ameliorated AGE-induced β-cell dysfunction and apoptosis both in vivo and in vitro. These effects were associated with decreased ROS production, down-regulated expression of p67(phox) and p22(phox), and reduced NADPH oxidase activity. These results suggest that sesamin protects β-cells from damage caused by AGEs through suppressing NADPH oxidase-mediated oxidative stress.

Topics: Animals; Antioxidants; Apoptosis; Cells, Cultured; Dioxoles; Glycation End Products, Advanced; Insulin; Insulin Secretion; Insulin-Secreting Cells; Lignans; Mice; Mice, Inbred C57BL; NADPH Oxidases; Oxidative Stress; Reactive Oxygen Species

Sesamin is naturally occurring lignan from sesame oil with putative antioxidant property. The present study was designed to investigate the protective role of sesamin against carbon tetrachloride induced oxidative liver injury. Male Wistar albino rats (180-200 g) were divided in to 5 groups (n=6). Hepatotoxicity was induced by the administration of CCl4 (0.1 ml/100 g bw., 50% v/v with olive oil) intraperitoneally. Sesamin was administered in two different dose (5 and 10 ml/kg bw) to evaluate the hepatoprotective activity. Sesamin significantly reduced the elevated serum liver marker enzymes (P<0.0001). Reduction of TBARS (P<0.01 and P<0.001) followed by enhancement of GSH., SOD and catalase (P<0.0001) in liver homogenate in sesamin treated groups shows the amelioration of oxidative stress induced by CCl4. Histopathological report also supported the hepatoprotection offered by sesamin. Sesamin effects in both the dose were in comparable to reference standard drug silymarin. From these above findings it has been concluded that sesamin ameliorate the oxidative liver injury in terms of reduction of lipid peroxidation and enhancement of liver antioxidant enzymes.

Topics: Animals; Antioxidants; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Dioxoles; Disease Models, Animal; Lignans; Lipid Peroxidation; Male; Oxidative Stress; Rats; Rats, Wistar

Sesamin, an active ingredient of Asiasarum heterotropoides, is known to exhibit many bioactive functions, but the effect thereof on vascular smooth muscle cell (VSMC) proliferation remains poorly understood. Hence, we explored the antiproliferative action of sesamin on VSMCs and the underlying mechanism thereof, focusing on possible effects of sesamin on cell cycle progression. Sesamin significantly inhibited platelet-derived growth factor (PDGF)-induced VSMC proliferation (inhibition percentage at 1, 5, and 10 μM sesamin was 49.8 ± 22.0%, 74.6 ± 19.9%, and 87.8 ± 13.0%, respectively) in the absence of cytotoxicity and apoptosis, and PDGF-induced DNA synthesis; and arrested cell cycle progression in the G0/G1-to-S phase. Sesamin potently inhibited cyclin D1 and CDK4 expression, pRb phosphorylation, and expression of the proliferating cell nuclear antigen (PCNA); and upregulated p27(KIP1), p21(CIP1), and p53. The results thus indicate that the antiproliferative effect of sesamin on PDGF-stimulated VSMCs is attributable to arrest of the cell cycle in G0/G1 caused, in turn, by upregulation of p27(KIP1), p21(CIP1), and p53, and inhibition of cyclin E-CDK2 and cyclin D1-CDK4 expression.

Topics: Animals; Aorta; Cell Cycle; Cell Proliferation; Cell Survival; Cyclin-Dependent Kinase Inhibitor p21; Cyclin-Dependent Kinase Inhibitor p27; Dioxoles; Lignans; Myocytes, Smooth Muscle; Phosphorylation; Platelet-Derived Growth Factor; Rats; RNA, Small Interfering; Signal Transduction; Up-Regulation

To observe the effect of sesamin (Ses) on pulmonary vascular remodeling in rats with monocrotaline ( MCT)-induced pulmonary hypertension (PH).. Totally 48 male Sprague-Dawley (SD) rats were fed adaptively for one week and then divided into the normal control group, the MCT group, the MCT +Ses (50 mg x kg(-1)) group and the MCT + Ses (100 mg x kg(-1)) group, with 12 rats in each group. The PH rat model was induced through the subcutaneous injection with MCT(60 mg x kg(-1)). After the administration for four weeks, efforts were made to measure the right ventricular systolic pressure( RVSP) and mean pulmonary artery pressure (mPAP) through right jugular vein catheterization, and isolate right ventricle( RV) and left ventricle( LV) +septum (S) and measure their length to calculate RV/ ( LV + S) and ratio of RV to tibial length. Pathologic changes in arterioles were observed by HE staining. Masson's trichrome stain was used to demonstrate changes in collagen deposition of arterioles. The alpha-smooth muscle actin (alpha-SMA) expression in pulmonary arteries was measured by immunohistochemisty. The total antioxidative capacity (T-AOC) and malondialdehyde (MDA) content in pulmonary arteries were determined by the colorimetric method. The protein expressions of collagen I, NOX2 and NOX4 were analyzed by Real-time PCR and Western blot.. After the administration for 4 weeks, Ses could attenuate RVSP and mPAP induced by MCT, RV/ (LV + S) and ratio of RV to Tibial length, alpha-SMA and collagen I expressions and remodeling of pulmonary vessels and right ventricle. Meanwhile, Ses could obviously inhibit the expressions of NOX2, NOX4 and MDA content and increase T-AOC.. Sesamin could ameliorate pulmonary vascular remodeling induced by monocrotaline in PH rats. Its mechanism may be related to expressions of NOX2 and NOX4 expression and reduction in oxidative stress injury.

Topics: Animals; Dioxoles; Disease Models, Animal; Drugs, Chinese Herbal; Humans; Hypertension, Pulmonary; Lignans; Lung; Male; Membrane Glycoproteins; Monocrotaline; NADPH Oxidase 2; NADPH Oxidase 4; NADPH Oxidases; Pulmonary Artery; Rats; Rats, Sprague-Dawley; Vascular Remodeling

Sesamolin and sesamin are representative lignans found in sesame seed. The present study was designed to demonstrate the anti-cancer activity of sesamolin achieved by increasing the expression level of NKG2D ligands on Raji cells, which are derived from Burkitt's lymphoma. The anti-cancer activity of sesamolin was also compared with that of sesamin. The cytolysis activity of NK cells against Raji was elevated by the pretreatment of sesamolin on Raji, but not by sesamin. We found that higher NKG2D ligand expression increased the sensitivity of sesamolin-treated Raji to NK cell lysis, resulting from a more active ERK signaling pathway. Our results provide evidence that targeting the ERK signaling pathway may enhance the antitumor activity of lignans and that there is a potential immunotherapeutic value for cancer treatment.

Topics: Antineoplastic Agents; Burkitt Lymphoma; Cell Line, Tumor; Cytotoxicity, Immunologic; Dioxoles; Humans; Killer Cells, Natural; Lignans; MAP Kinase Signaling System; Molecular Targeted Therapy; NK Cell Lectin-Like Receptor Subfamily K; Seeds; Sesamum; Up-Regulation

What is the central question of this study? Our aim was to examine whether sesamin can prevent a decline in exercise capacity in high-fat diet-induced diabetic mice. Our hypothesis was that maintenance of mitochondrial function and attenuation of oxidative stress in the skeletal muscle would contribute to this result. What is the main finding and its importance? The new findings are that sesamin prevents the diabetes-induced decrease in exercise capacity and impairment of mitochondrial function through the inhibition of NAD(P)H oxidase-dependent oxidative stress in the skeletal muscle. Sesamin may be useful as a novel agent for the treatment of diabetes mellitus.. We previously reported that exercise capacity and skeletal muscle mitochondrial function in diabetic mice were impaired, in association with the activation of NAD(P)H oxidase. It has been reported that sesamin inhibits NAD(P)H oxidase-induced superoxide production. Therefore, we examined whether the antioxidant sesamin could prevent a decline in exercise capacity in mice with high-fat diet (HFD)-induced diabetes. C57BL/6J mice were fed a normal diet (ND) or HFD, then treated or not with sesamin (0.2%) to yield the following four groups: ND, ND+Sesamin, HFD and HFD+Sesamin (n = 10 each). After 8 weeks, body weight, fat weight, blood glucose, insulin, triglyceride, total cholesterol and fatty acid were significantly increased in HFD compared with ND mice. Sesamin prevented the increases in blood insulin and lipid levels in HFD-fed mice, but did not affect the plasma glucose. Exercise capacity determined by treadmill tests was significantly reduced in HFD mice, but almost completely recovered in HFD+Sesamin mice. Citrate synthase activity was significantly decreased in the skeletal muscle of HFD mice, and these decreases were also inhibited by sesamin. Superoxide anion and NAD(P)H oxidase activity were significantly increased in HFD mice compared with the ND mice and were ameliorated by sesamin. Sesamin prevented the decline in exercise capacity in HFD-induced diabetic mice via maintenance of mitochondrial function, fat oxidation and attenuation of oxidative stress in the skeletal muscle. Our data suggest that sesamin may be useful as a novel agent for the treatment of diabetes mellitus.

Topics: Animals; Body Weight; Cell Line; Diabetes Mellitus, Experimental; Diet, High-Fat; Dioxoles; Exercise Tolerance; Lignans; Male; Mice, Inbred C57BL; Mitochondria, Muscle; Muscle, Skeletal; NADPH Oxidases; Oxidative Stress; Physical Conditioning, Animal; Superoxides

Sesamin, a major lignan derived from sesame seeds, has been reported to have many benefits and medicinal properties. However, its protective effects against fluoride-induced injury in kidney of fish have not been clarified. Previously we found that fluoride exposure caused damage and apoptosis in the kidneys of the common carp, Cyprinus carpio. In this study, the effects of sesamin on renal oxidative stress and apoptosis in fluoride-exposed fish were determined. The results showed that sesamin alleviated significantly fluoride-induced renal damage and apoptosis of carp in a dose-dependent manner, indicated by the histopathological examination and ultrastructural observation. Moreover, treatment with sesamin also inhibited significantly fluoride-induced remarkable enhancement of reactive oxygen species (ROS) production and oxidative stress, such as the increase of lipid peroxidation level and the depletion of intracellular reduced glutathione (GSH) level in kidney. To explore the underlying mechanisms of sesamin action, we found that activities of caspase-3 were notably inhibited by treatment with sesamin in the kidney of fluoride-exposed fish. Sesamin decreased the levels of p-JNK protein in kidney, which in turn inactivated pro-apoptotic signaling events by restoring the balance between mitochondrial pro- and anti-apoptotic Bcl-2 and Bax proteins and by decreasing the release of mitochondrial cytochrome c in kidney of fluoride-exposed fish. JNK was also involved in the mitochondrial extrinsic apoptotic pathways of sesamin effects against fluoride-induced renal injury by regulating the levels of p-c-Jun, necrosis factor-alpha (TNF-α) and Bak proteins. These findings indicated that sesamin could protect kidney against fluoride-induced apoptosis by the oxidative stress downstream-mediated change in the inactivation of JNK signaling pathway. Taken together, sesamin plays an important role in maintaining renal health and preventing kidney from toxic damage induced by fluoride.

Topics: Animals; Apoptosis; Carps; Caspase 3; Dioxoles; Fluorides; Glutathione; Kidney; Lignans; Lipid Peroxidation; MAP Kinase Signaling System; Mitochondria; Oxidative Stress; Phosphates; Reactive Oxygen Species; Signal Transduction; Water Pollutants, Chemical

The aim of this study was to verify the authenticity of sesame oils using combined analysis of stable isotope ratio, (1)H NMR spectroscopy, and fatty acid profiles of the oils. Analytical data were obtained from 35 samples of authentic sesame oils and 29 samples of adulterated sesame oils currently distributed in Korea. The orthogonal projection to latent structure discriminant analysis technique was used to select variables that most effectively verify the sesame oil authenticity. The variables include δ(13)C value, integration values of NMR peaks that signify the CH3 of n-3 fatty acids, CH2 between two C═C, protons from sesamin/sesamolin, and 18:1n-9, 18:3n-3, 18:2t, and 18:3t content values. The authenticity of 65 of 70 blind samples was correctly verified by applying the range of the eight variables found in the authentic sesame oil samples, suggesting that triple analysis is a useful approach to verify sesame oil authenticity.

Topics: Carbon Isotopes; Dioxoles; Fatty Acids; Lignans; Magnetic Resonance Spectroscopy; Sesame Oil

Leishmaniasis is a neglected tropical disease caused by Leishmania parasitic protozoa, which currently lacks efficient treatment. Natural products have shown promise as a potential source for antiprotozoal drugs. This work focuses on the antileishmanial potential of Sassafras albidum (Lauraceae) bark extract. The crude bark extract of S. albidum showed excellent antileishmanial activity with an IC50 value less than 12.5 μg/mL against promastigotes of L. amazonensis. The chloroform stem bark extract of S. albidum was subjected to preparative column chromatography. Five compounds were isolated, purified by recrystallization, and identified as sesamin, spinescin, β-sitosterol, hexatriacontanal, and 1-triacontanol. Antileishmanial and cytotoxic screening were performed on these compounds. Sesamin exhibited the best activity against L. amazonensis with an IC50 of 15.8 μg/mL and was not cytotoxic to mouse macrophage cells (CC50 > 100 μg/mL).

Topics: Dioxoles; Fatty Alcohols; Leishmania; Lignans; Microbial Sensitivity Tests; Plant Extracts; Sassafras; Sitosterols; Trypanocidal Agents

Sesamin (Ses) from Sesamun indicum seeds has potent antioxidants and anti-inflammatory effects.. This study focused on the antioxidant and anti-inflammatory effects of Ses on Carbon tetrachloride (CCl4)-induced hepatic fibrosis in experimental rats and the potential mechanism underlying the activation of NF-kB pathway.. Hepatic fibrosis was induced by interaperitoneally (i.p.) administered with 20% CCl4 in corn oil (2 mL/kg for 8 weeks) in rats. After 8 weeks, activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) were checked. The levels of protein carbonyls and antioxidant enzymes such as superoxide dismutase (SOD) and GSH-Px were determined after Ses administration. H&E and Masson's trichrome staining for histopathological changes of liver tissues were observed. Western blotting was used to detect expression of IL-6, cyclooxygenase-2 (COX-2), and NF-kB activation. Finally, the levels of hydroxyproline in liver tissues were also determined.. Ses decreased the release of liver enzymes - ALT, AST, and TBIL, reduced protein carbonyls, attenuated the reduction of SOD and GSH-Px activities induced by CCl4 in the liver tissue. It also significantly reduced the levels IL-6 and COX-2 in the liver caused by CCl4 by inhibition of NF-kB activation. Histological results indicated that Ses significantly improved the pathological lesions of liver fibrosis.. Ses exerted hepatoprotective effects possibly due to the antioxidant effect and suppressing the NF-kB activation.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Carbon Tetrachloride Poisoning; Dioxoles; Lignans; Liver Cirrhosis; Male; Rats; Rats, Sprague-Dawley

Sesamin (SM) and episesamin (ESM) are constituents of sesame seeds, which are used in health foods and considered to have various beneficial effects in the prevention of lifestyle-related diseases. P-Glycoprotein (P-gp) is an ATP-binding cassette transporter involved in drug absorption in the human gastrointestinal tract. A recent report indicated that SM influences P-gp-mediated drug transport. In the present study, we investigated whether SM and ESM inhibit P-gp in vitro, using Caco-2 cells and the typical P-gp substrates rhodamine123 (Rho123) and fexofenadine. SM and ESM showed no effect on accumulation of these compounds, indicating that SM and ESM do not influence P-gp function. In addition, an in vivo study using Rho123 indicated that SM and ESM do not affect absorption of P-gp substrates. Overall, these results suggest that health foods containing SM and ESM are unlikely to interact with P-gp substrates.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1; Biological Transport; Caco-2 Cells; Dioxoles; Drug Interactions; Food-Drug Interactions; Humans; Intestinal Absorption; Lignans; Male; Plant Extracts; Rats, Wistar; Rhodamine 123; Seeds; Sesamum; Terfenadine

To investigate the effect of serum containing sesamin on angiotension II (Ang II)-induced apoptosis in rat cardiomyocytes and the possible mechanisms.. H9c2 rat cardiomyocytes were preincubated with serum containing sesamin or blank serum for 12 h, followed by incubation with Ang II for 24 h. Cell viability was assessed by MTT assay and cell apoptosis was evaluated by flow cytometric analysis. Protein expression of BCL-2, BAX, Caspase-3, p47phox and superoxide dismutase (SOD) was determined by Western blot analysis. Levels of intracellular reactive oxygen species (ROS), total antioxidant capacity (T-AOC) and malondialdehyde (MDA) were measured colorimetrically.. Preincubation with serum containing sesamin significantly improved cell viability and suppressed cell apoptosis in H9c2 rat cardiomyocytes exposed to Ang II (P < 0.05 or P < 0.01), with the expression of BAX, Caspase-3 and p47phox protein down-regulated and BCL-2 and SOD protein up-regulated markedly (P < 0.05 or P < 0.01). The levels of T-AOC were effectively increased in serum containing sesamin groups, while the levels of intracellular ROS and MDA contents were decreased significantly (P < 0.05 or P < 0.01). Control serum had no influence on the above mentioned measurements.. Sesamin is capable of suppressing Ang II-induced apoptosis in H9c2 rat cardiomyocytes, which might be derived, at least partly, from amelioration of oxidative stress, regulation of BAX/BCL-2 protein expression and suppression of Caspase-3 protein expression.

Topics: Angiotensin II; Animals; Antioxidants; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Cell Line; Cell Survival; Dioxoles; Lignans; Malondialdehyde; Myocytes, Cardiac; Oxidative Stress; Proto-Oncogene Proteins c-bcl-2; Rats; Reactive Oxygen Species; Superoxide Dismutase

In order to provide the basis for quality standard and processing principle of processed Asari Radix et Rhizoma, an HPLC fingerprint of processed Asari Radix et Rhizoma was established and the contents of methyl eugenol and asarinin were determined.. The analytical column was Agligent Tc-C18 (250 mm x 4. 6 mm, 5 µm); A mixture of acetonitrile-0. 2% acetic acid solution was used as the mobile phase with gradient elution at the flow rate of 1. 0 mL/min. The wavelength was set at 285 nm and the column temperature was 30 °C.. The fingerprint of processed Asari Radix et Rhizoma was established. The asarinin peak was taken as the reference peak. 22 common peaks were assigned, and two peaks were confirmed by comparing with the reference standards. The difference of components was not significant among the various processed products except ginger, honey and fried coke products, but the contents of effective constituents were different among the processed products. The retention rate of methyl eugenol in processed products was in a descending order as follows: wine > vinegar > liquorice > alkali-vinegar > fried coke > rice water system > honey > ginger > salt system > alkali. Methyl eugenol was increased 10% ~ 20% with wine processing and retained more than 95% with vinegar. The retention rate of asarinin in processed products was in declining as: rice water system > liquorice > alkali-vinegar > honey > salt system > wine > ginger > vinegar > alkali > fried coke. The processing techniques increased the content of asarinin except the alkali and fried coke products, and asarinin was increased more than 35% with rice water, alkali-vinegar or liquorice processing.. The method is accurate and reliable, which can be used for the quality control of processed products of Asari Radix et Rhizoma.

Topics: Asarum; Chromatography, High Pressure Liquid; Dioxoles; Drugs, Chinese Herbal; Eugenol; Lignans; Plant Roots; Quality Control; Rhizome

A rapid, sensitive and selective liquid chromatography-tandem mass spectrometry was developed to determine two epimeric furofuran lignans (sesamin and asarinin) simultaneously from Asarum heterotropoides extract in rat plasma. Simple protein precipitation with acetonitrile was performed to extract analytes by using alantolactone as an internal standard. Chromatographic separation was achieved using a DIKMA Diamonsil C18 analytical column (4.6 mm × 150 mm, i.d., 5 µm) by isocratically eluting with a mobile phase consisting of methanol/5 mM ammonium acetate/formic acid (75:25:0.1, v/v/v) at a flow rate of 0.8 mL/min. Tandem mass spectrometric detection with an electrospray ionization interface was performed by multiple reaction monitoring in positive ionization mode. This method was validated according to specificity, sensitivity, linearity, intra- and inter-day precision (<10.7%) and accuracy (<2.3%) and recovery and stability in a concentration range of 25.0-15 000 ng/mL for sesamin and 5.00-3 000 ng/mL for asarinin. This method has been successfully applied in a pharmacokinetic study of A. heterotropoides extract containing sesamin and asarinin after this extract was orally administrated in rats.

Topics: Animals; Asarum; Chromatography, Liquid; Dioxoles; Lignans; Male; Plant Extracts; Rats; Rats, Wistar; Reproducibility of Results; Tandem Mass Spectrometry

A (1)H NMR-based metabolomics approach was used to explore the impact of dietary sesamin on the liver and white muscle metabolic profile of Atlantic salmon (Salmo salar). Fish were fed diets containing different n-6/n-3 fatty acid ratios (V0.5 or V1) and sesamin contents [without (S0), low (SL) 1.16 g/kg feed, and high (SH) 5.8 g/kg feed] for 4 months. Liver and white muscle extracts of aqueous polar and chloroform lipid phases were collected. Multivariate data analyses (PCA and OPLS-DA) of liver chloroform phase showed that high levels of sesamin affected the metabolic profile impartially of the n-6/n-3 ratio. In the aqueous phase, the metabolome of liver and white muscle were affected in fish fed an n-6/n-3 ratio of 1.0 and 0.5, respectively. With high inclusion of sesamin, the levels of several metabolites (e.g. glucose, glycogen, leucine, valine, creatine, carnitine, lactate, nucleosides) were increased. These metabolites are mainly associated with energy metabolism, suggesting that high sesamin inclusion affects liver and white muscle metabolism in fish. This is consistent with lower body weights found in fish fed high sesamin content.

Topics: Animals; Dioxoles; Lignans; Liver; Magnetic Resonance Spectroscopy; Metabolomics; Muscles; Salmo salar

Oxidative stress caused by doxorubicin (DOX) is believed to be a major underlying molecular mechanism of DOX-induced cardiotoxicity. Sesamin (Ses), an active component extracted from sesame seeds, exhibits antioxidative and anti-inflammatory effects. In the present study, possible protective mechanisms of Ses on DOX-induced cardiotoxicity were investigated in rats and cultured H9C2 cells. We demonstrated that Ses exhibits a significant protective effect on cardiac tissue in animal and cell models of DOX-induced cardiac injury. Moreover, Ses can ameliorate DOX-induced oxidative stress and mitochondrial damage. Further studies suggested that Ses is able to up-regulate the protein expression of Mn-SOD in normal rats and to restore the decreased expression of Mn-SOD in DOX-induced cardiac injury rats. Exposure to Ses or DOX alone slightly increased the protein expression of Sirt1; however, a more remarkable increase in Sirt1 protein level was detected in the Ses+DOX group. Treatment with a pan-sirtuin inhibitor (nicotinamide) or a Sirt1-specific inhibitor (EX-527) partially antagonised the effect of Ses on DOX-induced mitochondrial damage and completely abolished the effect of Ses on Mn-SOD expression. These findings indicate that the protective mechanisms of Ses on DOX-induced cardiotoxicity are involved in the alleviation of oxidative stress injury and Mn-SOD dysfunction, partially via the activation of Sirt1.

Topics: Animals; Antibiotics, Antineoplastic; Antioxidants; Dioxoles; Doxorubicin; Heart; Lignans; Male; Myocytes, Cardiac; Oxidative Stress; Rats; Rats, Sprague-Dawley; Sirtuin 1; Superoxide Dismutase

Sesamin (Ses), one of the major lignan derived from sesame seeds, has been reported to have many benefits and medicinal properties. However, its protective effects against carbon tetrachloride (CCl4) induced injury in liver have not been clarified. The aim of the present study was to investigate the hepatoprotective effects of sesamin on oxidative stress and apoptosis in mice exposed to CCl4. Our data showed that sesamin significantly prevented CCl4-induced hepatotoxicity in a dose-dependent manner, indicated by both diagnostic indicators of liver damage (serum aminotransferase activities) and histopathological analysis. Moreover, CCl4-induced profound elevation of reactive oxygen species (ROS) production and oxidative stress, as evidenced by increasing of lipid peroxidation level and depleting of the total antioxidant capacity (TAC) in liver, were suppressed by treatment with sesamin. Furthermore, TUNEL assay showed that CCl4-induced apoptosis in mouse liver was significantly inhibited by sesamin. In exploring the underlying mechanisms of sesamin action, we found that activities of caspase-3 were markedly inhibited by the treatment of sesamin in the liver of CCl4 treated mice. Sesamin increased expression levels of phosphorylated Jun N-terminal kinases (JNK) in liver, which in turn inactivated pro-apoptotic signaling events restoring the balance between mitochondrial pro- and anti-apoptotic Bcl-2 proteins and decreasing the release of mitochondrial cytochrome c in liver of CCl4 treated mice. JNK was also involved in the mitochondrial extrinsic apoptotic pathways of sesamin effects against CCl4 induced liver injury by regulating the expression levels of phosphorylated c-Jun proteins, necrosis factor-alpha (TNF-α) and Bak. In conclusion, these results suggested that the inhibition of CCl4-induced apoptosis by sesamin is due at least in part to its anti-oxidant activity and its ability to modulate the JNK signaling pathway.

Topics: Animals; Apoptosis; Carbon Tetrachloride; Caspase 3; Chemical and Drug Induced Liver Injury; Dioxoles; Enzyme Activation; Lignans; Liver; Male; MAP Kinase Kinase 4; Mice; Mice, Inbred ICR; Oxidative Stress; Phosphorylation; Reactive Oxygen Species

Osteoarthritis (OA) is a degenerative joint disease that progressively causes a loss of joint functions and the impaired quality of life. The most significant event in OA is a high degree of degradation of articular cartilage accompanied by the loss of chondroitin sulfate-proteoglycans (CS-PGs). Recently, the chondroprotective effects of sesamin, the naturally occurring substance found in sesame seeds, have been proved in a rat model of papain-induced osteoarthritis. We hypothesized that sesamin may be associated with possible promotion of the biosynthesis of CS-PGs in human articular chondrocytes. The aim of the study was to investigate the effects of sesamin on the major CS-PG biosynthesis in primary human chondrocyte. The effects of sesamin on the gene expression of the PG core and the CS biosynthetic enzymes as well as on the secretion of glycosaminoglycans (GAGs) in monolayer and pellet culture systems of articular chondrocytes. Sesamin significantly increased the GAGs content both in culture medium and pellet matrix. Real-time-quantitative PCR showed that sesamin promoted the expression of the genes encoding the core protein (ACAN) of the major CS-PG aggrecan and the biosynthetic enzymes (XYLT1, XYLT2, CHSY1 and CHPF) required for the synthesis of CS-GAG side chains. Safranin-O staining of sesamin treated chondrocyte pellet section confirmed the high degree of GAG accumulation. These results were correlated with an increased level of secreted GAGs in the media of cultured articular chondrocytes in both culture systems. Thus, sesamin would provide a potential therapeutic strategy for treating OA patients.

Topics: Adolescent; Adult; Aggrecans; Cartilage, Articular; Cells, Cultured; Chondrocytes; Chondroitin Sulfate Proteoglycans; Dioxoles; Gene Expression Regulation; Glucuronosyltransferase; Glycosaminoglycans; Humans; Lignans; Middle Aged; Multifunctional Enzymes; N-Acetylgalactosaminyltransferases; Pentosyltransferases; UDP Xylose-Protein Xylosyltransferase; Young Adult

The mechanisms underlying the preferential retention of a single compound (α-tocopherol (αT)) of the eight vitamin E compounds in the body are incompletely understood. We hypothesized that vitamin E metabolism and not the hepatic α-tocopherol transfer protein (TTP) is responsible for the discrimination against non-αT congeners.. TTP knockout and wild-type mice (n = 12/group) were fed equimolar concentrations of αT and γ-tocopherol (γT; 50 mg/kg diet each) alone or together with sesamin (2 g/kg diet) for 6 wk. Inhibition of vitamin E metabolism with sesamin, but not TTP knockout, increased γT tissue concentrations. TTP-expressing and TTP-free cells were incubated with equimolar concentrations of αT and γT (25 μmol/L each) with or without sesamin (2 μmol/L). The preferential degradation of γT independently of TTP expression was confirmed and a decrease in the production of the metabolite γ-carboxyethyl hydroxychromanol (CEHC) with increasing TTP expression revealed. Displacing γT from TTP in these cells by incubation with increasing αT concentrations enhanced the secretion of γ-CEHC in TTP-transfected cells, suggesting that TTP might protect γT from β-oxidation.. We conclude that vitamin E metabolism and not TTP controls γT concentrations in vivo and observed an interaction of TTP with vitamin E metabolism that results in reduced production of the metabolite γ-CEHC.

Topics: alpha-Tocopherol; Animals; Carrier Proteins; Chromans; Dioxoles; Female; gamma-Tocopherol; Hep G2 Cells; Humans; Lignans; Liver; Mice; Mice, Knockout; Mixed Function Oxygenases; Oxidation-Reduction; Propionates

Thirteen cold-pressed oils (Japanese quince seed, black caraway, flaxseed, rapeseed, hemp, peanut, sunflower, pumpkin, hazelnut, poppy, walnut, almond and sesame oil) manufactured by the same company over a 2-year period (2011-12) were assessed for lipophilic compounds. The presence of sesamin and sesamolin, two characteristic lignans of sesame oil, were detected in all tested plant oils. Both lignans were identified by NP-HPLC/FLD/DAD and confirmed by a RP-UPLC-ESI/MS(n) method. The lowest amount of sesamin and sesamolin was found for Japanese quince seed oil (0.10 and 0.27 mg/100 g), and the highest, excluding sesame oil, for almond oil (36.21 and 105.42 mg/100 g, respectively). The highly significant correlation between sesamolin and sesamin concentrations was found in all samples tested (r = 0.9999; p < 0.00001). These results indicate contamination of cold-pressed oils from the same source. This investigation highlights the fact that increasing the range of products manufactured by the same company can contribute to a lesser regard for the quality of the final product. Moreover, less attention paid to the quality of final product can be related to the health risks of consumers especially sensitive to allergens. Therefore, proper cleaning of processing equipment is needed to prevent cross-contact of cold-pressed oils.

Topics: Chromatography, Liquid; Dioxoles; Lignans; Plant Oils; Spectrometry, Mass, Electrospray Ionization

Stroke is one of the leading causes of neuronal death. Sesamin is known for neuroprotection by its antioxidant and anti-inflammatory properties but it lacks blood-brain barrier (BBB) activity. A panel of sesamin derivatives was screened and 3-bis (3-methoxybenzyl) butane-1,4-diol (BBD) was selected for high BBB activity and tested for its neuroprotective effect.. The focal cerebral ischemia of Sprague-Dawley rats and hypoxia models of murine BV-2 microglia or PC12 cells under oxygen/glucose deprivation were used for in vivo and in vitro test, respectively. Lipid peroxidation and superoxide dismutase (SOD) activity from the ischemic brain were tested and reactive oxygen species (ROS), cytokine production, prostaglandin (PGE2) and related signaling pathways from hypoxic cells were examined by ELISA or Western blot assay, respectively.. BBD showed a protective effect when given 90 min after the focal cerebral ischemia. It also reduced lipid peroxidation and preserved SOD activity from the ischemic brain. The mechanism of BBD was further confirmed by attenuating ROS, cytokine production, and PGE2 release from hypoxic BV-2 or PC12 cells. BBD significantly reduced hypoxia-induced c-Jun N-terminal kinases (JNK) and modulated AKT-1 and caspase-3 (survival and apoptotic pathways) in BV-2 cells, and inhibited hypoxia-induced JNK and cyclooxygenase-2 activation in PC12 cells.. The neuroprotective effect of BBD on ischemia/hypoxia models was involved with antioxidant and anti-inflammatory effects. The result would help the development of new CNS drug for protection of ischemia/hypoxia injury.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Blood-Brain Barrier; Brain Ischemia; Butylene Glycols; Cell Hypoxia; Dioxoles; Humans; Lignans; Lipid Peroxidation; Mice; Microglia; Neurons; Neuroprotective Agents; Rats; Reactive Oxygen Species; Signal Transduction; Superoxide Dismutase

Nutritional control has been proposed as a potential therapy for slowing the senescence of immune function and decreasing mortality. This study investigated whether sesamin could modify host defense systems and extend the lifespan of the nematode Caenorhabditis elegans.. Nematodes were fed standard food (the bacterium Escherichia coli strain OP50) supplemented with various doses of sesamin/γ-cyclodextrin inclusion compounds starting from young adulthood. The mean lifespan, muscle function, lipofuscin accumulation, protein carbonyl content, and stress resistance of the worms were examined. Then, C. elegans mutants harboring loss-of-function lesions in longevity- and host defense-related signaling pathways were supplemented with sesamin to identify the genes involved in the longevity effects.. Worms supplemented with sesamin displayed higher locomotion and prolongevity and produced offspring at levels similar to unsupplemented control animals. The growth curves of nematodes were similar to those of controls, suggesting that sesamin did not induce prolongevity effects through dietary restriction. Notably, sesamin made the worms more resistant to infection by Legionella pneumophila and more resistant to oxidative stressors such as paraquat and hydrogen peroxide and prolonged the lifespan of a mev-1 mutant that produces abundant superoxide anions. However, the accumulation of protein carbonyls and lipofuscin was similar in sesamin-exposed and control worms, suggesting that sesamin is unlikely to work simply as an antioxidant. Sesamin supplementation failed to extend the lifespan of loss-of-function mutants of daf-2, daf-16, pmk-1, and skn-1.. Sesamin enhances the host defense of C. elegans and increases the average lifespan via activation of both skn-1 (encoding a component of the p38 MAPK pathway) and daf-16 (encoding a component of the IGF-1 pathway).

Topics: Administration, Oral; Animals; Antioxidants; Caenorhabditis elegans; Dioxoles; Escherichia coli; gamma-Cyclodextrins; Insulin-Like Growth Factor I; Legionella pneumophila; Lignans; Longevity; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Protein Carbonylation; Salmonella enterica; Signal Transduction

(-)-Sesamin is a lignan present in sesam oil and a number of medicinal plants. It exerts various pharmacological effects, such as prevention of hyperlipidemia, hypertension, and carcinogenesis. Moreover, (-)-sesamin has chemopreventive and anticancer activity in vitro and in vivo. Multidrug resistance (MDR) of tumors leads to fatal treatment outcome in many patients and novel drugs able to kill multidrug-resistant cells are urgently needed. P-glycoprotein (MDR1/ABCB1) is the best known ATP-binding cassette (ABC) drug transporter mediating MDR. ABCB5 is a close relative to ABCB1, which also mediates MDR. We found that the mRNA expressions of ABCB1 and ABCB5 were not related to the 50% inhibition concentrations (IC50) for (-)-sesamin in a panel of 55 cell lines of the National Cancer Institute, USA. Furthermore, (-)-sesamin inhibited ABCB1- or ABCB5-overexpressing cells with similar efficacy than their drug-sensitive parental counterparts. In addition to ABC transporter-mediated MDR, we attempted to identify other molecular determinants of (-)-sesamin resistance. For this reason, we performed COMPARE and hierarchical cluster analyses of the transcriptome-wide microarray-based mRNA expression of the NCI cell panel. Twenty-three genes were identified, whose mRNA expression correlated with the IC50 values for (-)-sesamin. These genes code for proteins of different biological functions, i.e. ribosomal proteins, components of the mitochondrial respiratory chain, proteins involved in RNA metabolism, protein biosynthesis, or glucose and fatty acid metabolism. Subjecting this set of genes to cluster analysis showed that the cell lines were assembled in the resulting dendrogram according to their responsiveness to (-)-sesamin. In conclusion, (-)-sesamin is not involved in MDR mediated by ABCB1 or ABCB5 and may be valuable to bypass chemoresistance of refractory tumors. The microarray expression profile, which predicted sensitivity or resistance of tumor cells to (-)-sesamin consisted of genes, which do not belong to the classical resistance mechanisms to established anticancer drugs.

Topics: ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cell Line, Tumor; Cluster Analysis; Dioxoles; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Gene Expression Profiling; HEK293 Cells; Humans; Lignans; Neoplasms; Phytotherapy; Plant Extracts

Artemisia gorgonum (Asteraceae) is an endemic plant to the Cape Verde islands and plays an important role in traditional medicine. The chloroform extract of the plant aerial parts afforded six sesquiterpene lactones, two methoxylated flavonoids, two lignans, and one tetracyclic triterpene, which were isolated by chromatographic methods and their structure established by physical and spectroscopic techniques. The cytotoxic activity of the three major constituents, namely, arborescin, artemetin, and sesamin, was evaluated on neuroblastoma (SH-SY5Y), hepatocarcinoma (HepG2), and nontumoral bone marrow stromal (S17) cell lines. The application of different concentrations of the compounds significantly decreased tumor cells viability at different extents, especially at the highest concentrations tested. Arborescin is the most promising compound as it was able to reduce tumoral cell viability with an IC50 significantly lower (229-233 μM; p < 0.01) than that of S17 cells (445 μM). Arborescin and artemetin were less toxic to nontumoral cells than the antitumoral drug tested, etoposide. Our results indicate that arborescin has a significant cytotoxic activity in vitro, more pronounced on the cancer cell lines, confirming A. gorgonum as a source of potential antitumoral molecules.

Topics: Animals; Antineoplastic Agents, Phytogenic; Artemisia; Cell Line; Cell Line, Tumor; Dioxoles; Flavonoids; Humans; Lignans; Mice; Plant Components, Aerial; Plant Extracts; Sesquiterpenes, Guaiane

Topical preparations of Anemopsis californica have been used by Native American tribes in the southwestern United States and northern Mexico to treat inflammation and infections. We report results of bioassay-guided isolation conducted on a sample of A. californica roots. The furofuran lignans sesamin (1) and asarinin (2) were isolated and shown to have MIC values ranging from 23 to 395 µM against five different species of environmental nontuberculous mycobacteria. These findings are significant given that these bacteria can cause skin, pulmonary, and lymphatic infections. Crude A. californica extracts were analyzed by liquid chromatography-mass spectrometry, and it was determined that sesamin and asarinin were extracted at relatively high levels from the roots (1.7-3.1 g/kg and 1.1-1.7 g/kg, respectively), but at lower levels from the leaves (0.13 g/kg for both compounds). Our findings suggest that the majority of activity of crude A. californica root extracts against nontuberculous mycobacteria can be attributed to the presence of sesamin and asarinin. This paper is the first to report the isolation of these compounds from a member of the Saururaceae family, and the first to describe their activity against nontuberculous mycobacteria.

Topics: Anti-Bacterial Agents; Bacteria; Dioxoles; Lignans; Microbial Sensitivity Tests; Plant Extracts; Plant Roots; Saururaceae

Topics: Chemical and Drug Induced Liver Injury; Dioxoles; Humans; Lignans

In this study, we investigated the potential anti-inflammatory and antioxidative effects of sesamin on acute liver injury. Lead (Pb) causes oxidative damage and enhances the effects of low-dose lipopolysaccharide (LPS), inducing acute hepatic injury in rats.. Male Sprague-Dawley rats were given intraperitoneal injections of Pb acetate (5 mg/kg) and LPS (50 μg/kg) to induce liver injury, and we tested the effects of oral administration of sesamin (10 mg/kg) on liver damage. To assess the extent of acute hepatic injury in the rats, we measured the anti-inflammatory and antioxidant markers and relevant signaling pathways: serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), C-reactive protein (CRP), reactive oxygen species (ROS), tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, nitric oxide (NO), and cyclooxygenase-2 (COX-2), inducible NO synthase (iNOS) levels, mitogen-activated protein kinases (MAPKs), c-Fos, and GADD45β.. Sesamin significantly decreased the serum AST, ALT, and CRP levels in the rat model. In the Pb and LPS-stressed rats, sesamin administration reduced the serum levels of TNF-α, IL-1, IL-6, NO, and ROS generation, and liver tissue expressions of c-Jun N-terminal kinase (JNK), p38 MAPK, GADD45β, COX-2, and iNOS.. Collectively, these results demonstrate that sesamin is associated with antioxidant and anti-inflammatory activity. The observed effect of scavenging of ROS and NO and inhibiting the production of proinflammatory cytokines may be achieved through the suppression of COX-2, iNOS, and MAPK pathways in the acute hepatic injury rats.

Topics: Acute Disease; Animals; Chemical and Drug Induced Liver Injury; Dioxoles; Lignans; Lipopolysaccharides; Male; Organometallic Compounds; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Tumor Necrosis Factor-alpha

Allergic asthma is a lifelong airway condition that affects people of all ages. In recent decades, asthma prevalence continues to increase globally, with an estimated number of 250,000 annual deaths attributed to the disease. Although inhaled corticosteroids and β-adrenergic receptor agonists are the primary therapeutic avenues that effectively reduce asthma symptoms, profound side effects may occur in patients with long-term treatments. Therefore, development of new therapeutic strategies is needed as alternative or supplement to current asthma treatments. Sesamin is a natural polyphenolic compound with strong anti-oxidative effects. Several studies have reported that sesamin is effective in preventing hypertension, thrombotic tendency, and neuroinflammation. However, it is still unknown whether sesamin can reduce asthma-induced allergic inflammation and airway hyperresponsiveness (AHR). Our study has revealed that sesamin exhibited significant anti-inflammatory effects in ovalbumin (OVA)-induced murine asthma model. We found that treatments with sesamin after OVA sensitization and challenge significantly decreased expression levels of interleukin-4 (IL-4), IL-5, IL-13, and serum IgE. The numbers of total inflammatory cells and eosinophils in BALF were also reduced in the sesamin-treated animals. Histological results demonstrated that sesamin attenuated OVA-induced eosinophil infiltration, airway goblet cell hyperplasia, mucus occlusion, and MUC5AC expression in the lung tissue. Mice administered with sesamin showed limited increases in AHR compared with mice receiving vehicle after OVA challenge. OVA increased phosphorylation levels of IκB-α and nuclear expression levels of NF-κB, both of which were reversed by sesamin treatments. These data indicate that sesamin is effective in treating allergic asthma responses induced by OVA in mice.

Topics: Active Transport, Cell Nucleus; Allergens; Animals; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bronchoalveolar Lavage Fluid; Cytokines; Dioxoles; Eosinophils; Immunoglobulin E; Lignans; Lung; Male; Mice, Inbred BALB C; Mucus; NF-kappa B; Th2 Cells

Sesame oil is widely consumed as nutritious food, cooking oil, and in pharmaceuticals and food. In this study, the antinociceptive and anti-inflammatory properties of the sesame oil and sesamin were investigated. The sesame oil and sesamin reduced the number of abdominal contortions at the doses 100, 200, or 400 mg/kg. The first and second phases of the time paw licking were inhibited by sesame oil and sesamin (100, 200, or 400 mg/kg). After 90 min of treatment, sesame oil and sesamin increased the reaction time on a hot plate (200 or 400 mg/kg). Considering the tail-immersion assay, the sesame oil and sesamin produced significant effect after 60 min at the doses of 100, 200, or 400 mg/kg. After 4 h of application of the carrageenan, the sesame oil and sesamin were effective against the paw edema. The exudate volume and leucocyte migration were also reduced by sesame oil and sesamin. These results suggest that sesamin is one of the active compounds found in sesame oil and justify the antinociceptive and anti-inflammatory properties of this product.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Carrageenan; Dioxoles; Edema; Formaldehyde; Inflammation; Lignans; Male; Mice; Nociception; Pain; Pleurisy; Rats; Rats, Wistar; Sesame Oil; Toxicity Tests, Acute

Foam cells formation as a result of the uncontrolled cytophagy of modified cholesterol by macrophages plays a key role in the occurrence and development of atherosclerosis. Sesamin is an active constituent of Sesamum indicum which has been shown to possess multiple pharmacological activities. In this work, we investigated the effects of sesamin on foam cell formation and cholesterol efflux in RAW264.7 macrophages. Sesamin dose-dependently inhibited the enhanced cholesterol accumulation elicited by oxidized low-density lipoprotein cholesterol (oxLDL) in RAW264.7 cells. Treatment with sesamin (10 μM) significantly enhanced cholesterol efflux mediated by high-density lipoprotein (HDL). Realtime quantitative PCR and luciferase assays showed that sesamin significantly increased the mRNA levels of PPARγ, LXRα, and ABCG1, and increased the transcriptional activity of PPARγ. The stimulating effect of sesamin on cholesterol efflux was substantially inhibited by the co-treatment with GW9662, a potent inhibitor of PPARγ. These results suggest that sesamin is a new inhibitor of foam cell formation that may stimulate cholesterol efflux through upregulation of the PPARγ-LXRα-ABCG1 pathway.

Topics: Animals; Biological Transport; Cell Line; Cholesterol; Dioxoles; Lignans; Macrophages; Mice

Airway fibrosis, which is a crucial pathological condition occurring in various types of pulmonary disorders, is characterized by accumulation and activation of fibroblast cells, deposition of extracellular matrix (ECM) proteins, and increase of airway basement membrane. Transforming growth factor beta 1 (TGF-β1) is the principal profibrogenic cytokine that is responsible for fibrotic responses. In the present study, we aimed to investigate the antifibrotic effects of the natural polyphenolic compound, sesamin, on TGF-β1-induced fibroblast proliferation and activation, epithelial-mesenchymal transition (EMT), and ovalbumin (OVA)-induced airway fibrosis in vivo. We found that sesamin attenuated TGF-β1-induced proliferation of cultured lung fibroblasts. Sesamin inhibited TGF-β1-stimulated expression of alpha smooth muscle actin (α-SMA), suggesting that sesamin plays an inhibitory role in fibroblast activation. Sesamin blocked upregulation of the mesenchymal markers (fibronectin and vimentin) and downregulation of the epithelial marker (E-cadherin), indicating an inhibitory effect on TGF-β1-induced EMT in A549 cells. TGF-β1-induced Smad3 phosphorylation was also significantly reduced by sesamin in both cultured fibroblast and A549 cells. In the airway fibrosis induced by OVA in mice, sesamin inhibited the accumulation of α-SMA-positive cells and expression of collagen I in the airway. Histological studies revealed that sesamin protected against subepithelial fibrosis by reducing myofibroblast activation and collagen accumulation in the ECM. OVA-induced thickening of basement membrane was significantly alleviated in animals receiving sesamin treatments. These results suggest a therapeutic potential of sesamin as an antifibrotic agent.

Topics: Actins; Animals; Basement Membrane; Cell Line; Cell Proliferation; Collagen Type I; Dioxoles; Down-Regulation; Epithelial-Mesenchymal Transition; Extracellular Matrix Proteins; Fibroblasts; Fibrosis; Humans; Lignans; Lung Diseases; Mice; Mice, Inbred C57BL; Respiratory Mucosa; Signal Transduction; Smad3 Protein; Transforming Growth Factor beta1

Recent studies have demonstrated that side population (SP) cells isolated from various cancer cell lines and primary tumors possess stem cell-like properties. Sesamin, a food-derived agent, possesses anti-cancer activities both in vitro and in vivo. The present study was designed to determine whether sesamin also have effects on cancer stem-like SP cells from gallbladder cancer (GBC).. In this study, we sorted SP cells by flow cytometry. SP cells were cultured and treated with sesamin. Tumor-sphere formation, colony formation, Matrigel invasion and tumorigenic potential were determined. Expression of nuclear NF-κB, IL-6, p-Stat3, Twist, E-cadherin and Vimentin was measured by Western blot, immunofluorescence staining or RT-PCR analysis. Nuclear NF-κB activity and IL-6 protein level were assessed with ELISA. Xenograft tumors were generated in nude mice.. After treated with sesamin, SP cells differentiated into cells expressing the epithelial marker (E-cadherin). Sesamin effectively affected SP cells stem cell-like characteristics (i.e., tumor-sphere formation, colony-formation, Matrigel invasion), weakened the drug-resistance of SP cells and inhibited tumor growth both in vitro and in vivo. Treatment with sesamin significantly reduced the expression of nuclear NF-κB, IL-6, p-Stat3, Twist and Vimentin (a mesenchymal marker) in SP cells. Nuclear NF-κB activity and IL-6 level were also decreased after treatment with sesamin.. Food-derived sesamin directs the epithelial differentiation of cancer stem-like SP cells from GBC, which is associated with attenuation of NF-κB-IL-6-Stat3-Twist signal pathway.

Topics: Analysis of Variance; Animals; Cadherins; Carcinoma; Cell Differentiation; Cell Line, Tumor; Dioxoles; Female; Gallbladder Neoplasms; Humans; Interleukin-6; Lignans; Mice; Mice, Nude; Neoplastic Stem Cells; NF-kappa B; Side-Population Cells; Signal Transduction; Xenograft Model Antitumor Assays

To study the chemical constituents of Pattra Medicine Euodia lepta in Xishuangbanna of Yunnan Province.. The chemical constituents were isolated and purified by chromatographic techniques, and identified by NMR, MS and other spectral methods.. In 60% ethanol extract from the stems,and 95% ethanol extract from the leaves, six compounds and two compounds were isolated and identified as pachypodol( 1) ,3-(3-methyl-but-2-enyl )umbelliferone(2),7-demethylsuberosin (3),beta-sitosterol (4),3,7-dimethoxy kaempferol(5), euolitrine(6), sesamin(7) and p-O-geranyl coumaric acid(8), respectively.. Compound 7 is obtained from Euodia genus for the first time,and compound 8 is obtained from domestic Euodia lepta for the first time.

Topics: China; Coumaric Acids; Dioxoles; Evodia; Furocoumarins; Lignans; Plant Leaves; Plant Stems; Sitosterols

Chemokines play important roles in the pathogenesis of asthmatic inflammation. Sesamin, a class of phytoestrogen isolated from sesame seed Sesamum indicum, is recently regarded as an anti-inflammatory agent. However, the effects of sesamin on asthma-related chemokines are unknown. To this end, we investigated the effects of sesamin on the expression interferon-γ-inducible protein-10 (IP-10/CXCL10), macrophage-derived chemokine (MDC/CCL22), growth-related oncogene-α (GRO-α/CXCL1) and tumor necrosis factor (TNF)-α in human monocytes.. Cells were pretreated with sesamin before lipopolysaccharide (LPS) stimulation. IP-10, MDC, GRO-α and TNF-α were measured by ELISA. Involved receptors and intracellular signaling were investigated by receptor antagonists, pathway inhibitors, western blotting and chromatin immunoprecipitation.. Sesamin suppressed LPS-induced MDC in THP-1 and human primary monocytes. Sesamin suppressed LPS-induced IP-10 in THP-1 cells, but not human primary monocytes. Sesamin had no effects on LPS-induced GRO-α and TNF-α expression in THP-1 and human primary monocytes. The suppressive effect of sesamin on MDC was reversed by the estrogen receptor (ER) and peroxisomal proliferator-activated receptor (PPAR)-α antagonists. Sesamin suppressed LPS-induced phosphorylation of mitogen-activated protein kinase (MAPK)-p38 and nuclear factor kappa B (NFκB)-p65. Sesamin suppressed histone H3/H4 acetylation in the MDC promoter region.. Sesamin suppressed LPS-induced MDC expression via the ER, the PPAR-α, the MAPK-p38 pathway, the NFκB-p65 pathway and the epigenetic regulation. Sesamin may have therapeutic potential in preventing and treating asthma.

Topics: Anti-Inflammatory Agents; Asthma; Cell Line, Tumor; Chemokine CCL22; Chemokine CXCL1; Chemokine CXCL10; Dioxoles; Epigenesis, Genetic; Histones; Humans; Lignans; Lipopolysaccharides; Monocytes; p38 Mitogen-Activated Protein Kinases; Phosphorylation; PPAR alpha; Promoter Regions, Genetic; Receptors, Estrogen; Seeds; Sesamum; Signal Transduction; Transcription Factor RelA; Tumor Necrosis Factor-alpha

Sesaminol triglucoside is a major lignin in sesame meal and has a methylenedioxyphenyl group and multiple functions in vivo. As a tetrahydrofurofuran type lignan, sesaminol triglucoside is metabolized to mammalian lignans. This investigation studies the effect of sesaminol triglucoside and its tetrahydrofuranoid metabolites (sesaminol, 2-episesaminol, hydroxymethyl sesaminol-tetrahydrofuran, enterolactone, and enterodiol) on gene expression in primary rat hepatocytes using a DNA microarray. Sesame lignans significantly affected the expression of xenobiotic-induced transcripts of cytochrome P450, solute carrier (SLC), and ATP-binding cassette (ABC) transporters. Changes in gene expression were generally greater in response to metabolites with methylenedioxyphenyl moieties (sesaminol triglucoside, sesaminol, and 2-episesaminol) than to the tetrahydrofuranoid metabolites (hydroxymethyl sesaminol-tetrahydrofuran, enterolactone, and enterodiol). Tetrahydrofuran lignans, such as sesaminol triglucoside, sesamin, hydroxymethyl sesaminol-tetrahydrofuran, and sesaminol changed the expression of ABC transporters.

Topics: 4-Butyrolactone; Animals; ATP-Binding Cassette Transporters; Cytochrome P-450 Enzyme System; Dioxoles; Furans; Gene Expression; Gene Expression Profiling; Glucosides; Hepatocytes; Inactivation, Metabolic; Lignans; Liver; Mammals; Plant Extracts; Rats, Sprague-Dawley; Seeds; Sesamum

To investigate the protective effect of sesamin against cadmium chloride (CdCl2)-induced cardiotoxicity in rats.. Fifty male Wistar rats were randomly assigned to five groups: control group, CdCl2 group, and low-, middle-, and high-dose sesamin groups. The control group was given normal saline. The CdCl2 group and sesamin groups were intraperitoneally injected with CdCl2 (5 mg/kg×2 d), and the low-, middle-, and high-dose sesamin groups were given 20, 40, and 80 mg/kg sesamin, respectively. All treatments lasted for four weeks. ECG was measured by a physiological recorder, and serum myocardial enzyme levels were determined by biochemical assay. The heart was weighed, and heart tissues were used in histopathological examination and determination of malondialdehyde (MDA) level.. Compared with the control group, the CdCl2 group showed significantly higher levels of serum CK and CK-MB, an increased heart coefficient, significant ST-segment elevation, and higher level of MDA in myocardial tissue (P < 0.05). Histopathological analysis showed edema of myocardial tissues and cells, myocardial fibers disorder, karyopyknosis, and uneven or deep staining of nuclear chromatin. Different doses of sesamin relieved the myocardial pathological changes induced by CdCl2, and high-dose sesamin was the most effective. The middle- and high-dose sesamin groups showed significantly reduced serum CK and CK-MB levels compared with the CdCl2 group (P < 0.05). The heart coefficient of the high-dose sesamin group (0.19±0.01%) was significantly lower than that of the CdCl2 group (0.21±0.01%) (P < 0.05). Myocardial MDA levels of the three sesamin groups (42.32±4.65, 36.71±5.34, and 33.12±4.62 nmol/mg pro, respectively) were all significantly lower than that of the CdCl2 group (55.87±3.65 nmol/mg pro) (P < 0.05).. Sesamin can relieve myocardial injury induced by CdCl2, and one possible mechanism is the enhancement of antioxidant capacity of myocardial tissue.

Topics: Animals; Cadmium Chloride; Creatine Kinase, MB Form; Dioxoles; Heart; Lignans; Male; Malondialdehyde; Myocardium; Rats; Rats, Wistar

Sesamin is a major component in lignans of sesame seed oil, known to possess potent anti-oxidative capacity. In this study, the variation of heme oxygenase (HO)-1, a kind of anti-oxidative enzyme, by sesamin in murine macrophage cell line RAW 264.7 cells was investigated. Lipopolysaccharide (LPS; 10μg/ml) exposure tended to increase HO-1 protein expression. Co-treatment with 100μM sesamin for 12h up-regulated the HO-1 protein level increased by LPS; however, HO-1 mRNA was unaffected. Sesamin delayed the reversal, by the protein synthesis inhibitor cycloheximide (1μM), of the LPS-induced increase of HO-1 protein level. Meanwhile, sesamin suppressed LPS-induced expression of inducible nitric oxide (NO) synthase (iNOS) protein and associated NO release. LPS-induced increase of iNOS protein expression was also reversed by cycloheximide, which was not affected by sesamin, unlike HO-1. To clarify the mechanisms that underlie the up-regulation of HO-1 protein level by sesamin, the human embryonic kidney (HEK) 293T cell line transfected with Flag-tagged HO-1 was used. A proteasome inhibitor, MG-132 (10μM), stabilized HO-1 protein in HEK 293T cells. Co-treatment with sesamin decreased ubiquitinated HO-1 protein accumulation by MG-132. However, sesamin did not affect the proteasome activity. These findings suggest that sesamin disturbs the degradation of HO-1 protein through inhibiting its ubiquitination, resulting in HO-1 protein up-regulation.

Topics: Animals; Cell Line; Dioxoles; HEK293 Cells; Heme Oxygenase-1; Humans; Lignans; Macrophages; Membrane Proteins; Mice; Sesame Oil; Ubiquitination; Up-Regulation

Stroke is a severe neurological disorder characterized by the abrupt loss of blood circulation into the brain resulting into wide ranging brain and behavior abnormalities. The present study was designed to evaluate molecular mechanism by which sesamin (SES) induces neuroprotection in mouse model of ischemic stroke. The results of this study demonstrate that SES treatment (30 mg/kg bwt) significantly reduced infarction volume, lipid per-oxidation, cleaved-caspase-3 activation, and increased GSH activity following MCAO in adult male mouse. SES treatment also diminished iNOS and COX-2 protein expression, and significantly restored SOD activity and protein expression level in the ischemic cortex of the MCAO animals. Furthermore, SES treatment also significantly reduced inflammatory and oxidative stress markers including Iba1, Nox-2, Cox-2, peroxynitrite compared to placebo MCAO animals. Superoxide radical production, as studied by DHE staining method, was also significantly reduced in the ischemic cortex of SES treated compared to placebo MCAO animals. Likewise, downstream effects of superoxide free radicals i.e. MAPK/ERK and P38 activation was also significantly attenuated in SES treated compared to placebo MCAO animals. In conclusion, these results suggest that SES induces significant neuroprotection, by ameliorating many signaling pathways activated/deactivated following cerebral ischemia in adult mouse.

Topics: Animals; Brain Ischemia; Dioxoles; Disease Models, Animal; Encephalitis; Infarction, Middle Cerebral Artery; Lignans; Male; Mice; Mice, Inbred C57BL; Microglia; Neuroprotective Agents; Oxidative Stress; Signal Transduction; Stroke

Foam cell formation resulting from disrupted macrophage cholesterol efflux, which is triggered by PPARγ1 and LXRα, is a hallmark of atherosclerosis. Sesamin and sesame oil exert anti-atherogenic effects in vivo. However, the exact molecular mechanisms underlying such effects are not fully understood.. This study examines the potential effects of sesamin (0, 25, 50, 75, 100 μM) on PPARγ1 and LXRα expression and transcriptional activity as well as macrophage cholesterol efflux.. PPARγ1 and LXRα expression and transcriptional activity are assessed by luciferase reporter assays. Macrophage cholesterol efflux is evaluated by ApoAI-specific cholesterol efflux assays.. The 50 μM, 75 μM, and 100 μM concentrations of sesamin up-regulated the expression of PPARγ1 (p<0.001, p<0.001, p<0.001, respectively) and LXRα (p=0.002, p<0.001, p<0.001, respectively) in a concentration-dependent manner. Moreover, 75 μM and 100 μM concentrations of sesamin led to 5.2-fold (p<0.001) and 6.0-fold (p<0.001) increases in PPAR transcriptional activity and 3.9-fold (p<0.001) and 4.2-fold (p<0.001) increases in LXR transcriptional activity, respectively, in a concentration- and time-dependent manner via MAPK signaling. Consistently, 50 μM, 75 μM, and 100 μM concentrations of sesamin improved macrophage cholesterol efflux by 2.7-fold (p<0.001), 4.2-fold (p<0.001), and 4.2-fold (p<0.001), respectively, via MAPK signaling.. Our findings shed light on the molecular mechanism(s) underlying sesamin’s anti-atherogenic effects, which seem to be due, at least in part, to its ability to up-regulate PPARγ1 and LXRα expression and transcriptional activity, improving macrophage cholesterol efflux. We anticipate that sesamin may be used as a therapeutic agent for treating atherosclerosis.

Topics: Animals; Anticholesteremic Agents; Cells, Cultured; CHO Cells; Cholesterol; Cricetinae; Cricetulus; Dioxoles; Lignans; Liver X Receptors; Macrophages, Peritoneal; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; Orphan Nuclear Receptors; PPAR gamma; Signal Transduction; Transfection; Up-Regulation

Sesamin is one of the major lignans in sesame seeds with antihyperlipidemic, antioxidative and antihypertensive activities. The aim of this study was to examine the effects of sesamin on arterial function in spontaneously hypertensive rats (SHRs).. SHRs were orally administered sesamin (40, 80 and 160 mg·kg(-1)·d(-1)) for 16 weeks. After the rats were killed, thoracic aortas were dissected out. The vasorelaxation responses of aortic rings to ACh and nitroprusside were measured. The expression of eNOS and NADPH oxidase subunits p47(phox) and p22(phox) in aortas were detected using Western blotting and immunohistochemistry. Aortic nitrotyrosine was measured with ELISA. The total antioxidant capacity (T-AOC) and MDA levels in aortas were also determined.. The aortic rings of SHRs showed significantly smaller ACh-induced and nitroprusside-induced relaxation than those of control rats. Treatment of SHRs with sesamin increased both the endothelium-dependent and endothelium-independent relaxation of aortic rings in a dose-dependent manner. In aortas of SHRs, the level of T-AOC and the expression of nitrotyrosine, p22(phox) and p47(phox) proteins were markedly increased, while the level of MDA and the expression of eNOS protein were significantly decreased. Treatment of SHRs with sesamin dose-dependently reversed these biochemical and molecular abnormalities in aortas.. Long-term treatment with sesamin improves arterial function in SHR through the upregulation of eNOS expression and downregulation of p22(phox) and p47(phox) expression.

Topics: Animals; Aorta, Thoracic; Dioxoles; Down-Regulation; Hypertension; Lignans; Male; NADPH Oxidases; Nitric Oxide Synthase Type III; Organ Culture Techniques; Protein Subunits; Random Allocation; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Up-Regulation

Thirteen compounds belonging to different classes of alkaloids (1-9) and lignans (10-13), isolated from the methanol extract of roots of the African medicinal plant Zanthoxylum capense, were assayed for their ability as apoptosis inducers in HCT116 colon carcinoma cells. The cytotoxicity of these compounds was evaluated in HCT116 colon carcinoma cells by the MTS assay. Out of the tested compounds, three benzophenanthridine alkaloids (1, 4, and 7), a dibenzyl butyrolactone lignan (10), and two 2-arylbenzofuran neolignans (12 and 13) displayed significant cytotoxicity to HCT116 cells, confirmed by the Guava ViaCount viability assay. The selected compounds (1, 4, 7, 10, 12, and 13) were further tested for apoptosis induction activity in HCT116 cells, by evaluation of nuclear morphology following Hoechst staining, and by caspase-3 like activity assays. Morphologic evaluation of HCT116 nuclei following Hoechst staining and fluorescence microscopy revealed that compounds 1, 4, 7, 10, 12, and 13 induced apoptosis in HCT116 colon carcinoma cells, producing similar, or higher, apoptosis levels when compared with 5-fluorouracil (5-FU), the cornerstone cytotoxic used in colon cancer treatment for several decades. In fact, HCT116 cells developed morphological changes characteristic of apoptosis, including chromatin condensation, nuclear fragmentation and formation of apoptotic bodies. Importantly, compounds 4 and 13 at 20 μM were the most promising in this study, inducing respectively ∼11- and 7-fold increases in apoptotic cells as compared to vehicle control, whereas 5-FU increased apoptosis by ∼2-fold. Apoptosis induction for compounds 4 and 13 was further confirmed by caspase-3-like activity assays, which showed respectively ∼2- and 1.5-fold increases in caspase-3-like activity compared to vehicle control. These results suggested that specific benzophenanthridine alkaloids and 2-arylbenzofuran neolignans isolated from Zanthoxylum capense show strong anticancer activity in HCT116 colon carcinoma cells.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Benzophenanthridines; Dioxoles; Drug Screening Assays, Antitumor; HCT116 Cells; Humans; Indole Alkaloids; Lignans; Plants, Medicinal; Quinazolines; Quinolines; Zanthoxylum

Silica gel column chromatography combined with high performance counter-current chromatography (HPCCC) was employed for the separation of potential anti-tumor compounds from a petroleum ether fraction of a crude extract of Zanthoxylum ailanthoides Sieb. & Zucc. This traditional Chinese medicine was recently found to display high inhibitory activity against A-549 human cancer cells in vitro and Lewis lung cancer in vivo. A 75% aqueous ethanol extract of the stem bark of Z. ailanthoides was fractionated with petroleum ether, ethyl acetate and n-butanol. In this paper, the petroleum ether fraction was pre-separated by silica gel column chromatography with a petroleum ether-ethyl acetate gradient. Two fractions were further separated and purified by HPCCC using n-hexane-ethyl acetate-methanol-water (3:1:2:1, v/v) and petroleum-ethyl acetate-methanol-water (8:6:7:7, v/v). Finally, coumarins and lignans including luvangetin, xanthyletin, hinokinin and asarinin were isolated and identified by MS, (1)H and (13)C NMR. In total, 56mg of xanthyletin (1), 140mg of hinokinin (2), 850mg of luvangetin (3) and 74mg of asarinin (4) were obtained from approximately 50g of petroleum ether extract, in 96.0%, 94.0%, 99.0% and 94.0% purity, respectively, as determined by HPLC. The separation method proved to be efficient, especially for those minor components.

Topics: 4-Butyrolactone; Antineoplastic Agents, Phytogenic; Benzodioxoles; Cell Line, Tumor; Cell Survival; Coumarins; Countercurrent Distribution; Dioxoles; Humans; Lignans; Plant Bark; Silica Gel; Zanthoxylum

We have shown that intake of sesame seed and its lignan increases vitamin E concentrations and decreases urinary excretion levels of vitamin E metabolites in male Wistar rats, suggesting inhibition of vitamin E catabolism by sesame lignan. The aim of this study was to examine whether dietary sesame seed also increased vitamin K concentrations, because its metabolic pathway is similar to that of vitamin E. To test the effect of sesame lignan on vitamin K concentrations, male Wistar rats were fed a control diet or a diet with 0.2% sesamin (a sesame lignan) for 7 d in experiment 1. Liver phylloquinone (PK), menaquinone-4 (MK-4), and γ-tocopherol were greater in rats fed sesamin than in control rats. To test the effect of sesame seed on vitamin K concentrations, male Wistar rats were fed a control diet or a diet with 1, 5, or 10% sesame seed for 3 d in experiment 2. Liver and kidney PK and γ-tocopherol but not MK-4 were greater in rats fed sesame seed than in control rats, although differences in dietary amounts of sesame seed did not affect the PK concentrations. For further confirmation of the effect of sesame seed, male Wistar rats were fed a control diet or a diet with 20% sesame seed for 40 d in experiment 3. Kidney, heart, lung, testis, and brain PK and brain MK-4 were greater in rats fed sesame seed than in control rats. The present study revealed for the first time, to our knowledge, that dietary sesame seed and sesame lignan increase not only vitamin E but also vitamin K concentrations in rat tissues.

Topics: Animals; Brain; Diet; Dioxoles; gamma-Tocopherol; Heart; Kidney; Lignans; Liver; Lung; Male; Rats; Rats, Wistar; Seeds; Sesamum; Testis; Vitamin K 1; Vitamin K 2

Endothelial protein C receptor (EPCR) plays a pivotal role in augmenting Protein C activation by the thrombin-thrombomodulin complex. The activity of EPCR is markedly changed by ectodomain cleavage and release as the soluble protein (sEPCR). The EPCR shedding is mediated by the tumor necrosis factor-α converting enzyme (TACE). Epi-sesamin (ESM), from the roots of Asarum siebodlii, is known to exhibit anti-allergic and anti-fungal activities. However, little is known about the effects of ESM on EPCR shedding.. We investigated this issue by monitoring the effects of ESM on phorbol-12-myristate 13-acetate (PMA), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and cecal ligation and puncture (CLP)-mediated EPCR shedding.. Data showed that ESM induced potent inhibition of PMA, TNF-α, IL-1β, and CLP-induced EPCR shedding, likely through suppression of TACE expression. In addition, treatment with ESM resulted in a reduction of PMA-stimulated phosphorylation of p38, extracellular regulated kinases (ERK) 1/2, and c-Jun N-terminal kinase (JNK).. Given these results, ESM should be viewed as a candidate therapeutic agent for treatment of various severe vascular inflammatory diseases via inhibition of EPCR shedding.

Topics: Animals; Anti-Inflammatory Agents; Antigens, CD; Cells, Cultured; Dioxoles; Endothelial Protein C Receptor; Human Umbilical Vein Endothelial Cells; Humans; Interleukin-1beta; Lignans; Male; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; Receptors, Cell Surface; Sepsis; Tetradecanoylphorbol Acetate; Tumor Necrosis Factor-alpha

Sesamin, one of the most abundant lignans in sesame seeds, has been shown to exhibit various pharmacological effects. The aim of this study was to elucidate whether sesamin promotes cell cycle arrest and induces apoptosis in HepG2 cells and further to explore the underlying molecular mechanisms. Here, we found that sesamin inhibited HepG2 cell growth by inducing G2/M phase arrest and apoptosis. Furthermore, sesamin suppressed the constitutive and interleukin (IL)-6-induced signal transducer and activator of transcription 3 (STAT3) signalling pathway in HepG2 cells, leading to regulate the downstream genes, including p53, p21, cyclin proteins and the Bcl-2 protein family. Our studies showed that STAT3 signalling played a key role in sesamin-induced G2/M phase arrest and apoptosis in HepG2 cells. These findings provided a molecular basis for understanding of the effects of sesamin in hepatocellular carcinoma tumour cell proliferation. Therefore, sesamin may thus be a potential chemotherapy drug for liver cancer.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Carcinoma, Hepatocellular; Cell Cycle; Cell Cycle Checkpoints; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Dioxoles; Gene Expression Regulation, Neoplastic; Hep G2 Cells; Humans; Interleukin-6; Lignans; Liver Neoplasms; Phytotherapy; Plant Extracts; Seeds; Sesamum; Signal Transduction; STAT3 Transcription Factor; Tumor Suppressor Protein p53

Two impurities in the natural vitamin E extracted from oil deodorizer distillate were separated and characterized by high-performance liquid chromatography (HPLC), gas chromatography-mass spectrometry (GC-MS) and Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS). The impurities were purified and collected by normal-phase HPLC. The accurate masses were determined using FTICR-MS and fragmentation behavior was studied by GC-MS. The results showed that the impurities had identical MS spectra and similar electron impact (EI) fragmentation patterns. Based on the spectra, the structures of the two impurities were proposed as the enantiomers of sesamin. The presented method is rapid and effective, and can be applied for the food safety to the vitamin E manufacturing industry.

Topics: Chromatography, High Pressure Liquid; Dioxoles; Gas Chromatography-Mass Spectrometry; Lignans; Vitamin E

Sesamin (SM) and epi-sesamin (ESM) were isolated from Asarum sieboldii and their anticoagulant activities were examined by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT), and the activities of cell-based thrombin and activated factor X (FXa). In addition, the effects of SM and ESM on the expression of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were tested in tumor necrosis factor-α (TNF-α) activated human umbilical vein endothelial cells (HUVECs). Treatment with ESM, but not SM, resulted in significantly prolonged aPTT and PT and inhibition of the activities of thrombin and FXa, and ESM inhibited production of thrombin and FXa in HUVECs; and ESM inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. In accordance with these anticoagulant activities, ESM elicited anticoagulant effects in mice. In addition, treatment with ESM, but not SM, resulted in the inhibition of TNF-α-induced production of PAI-1, and treatment with ESM resulted in a significant reduction of the PAI-1 to t-PA ratio. Of particular interest, inhibition of the anticoagulant activity by ESM was more potent than that by SM, likely due to differences between their three-dimensional structures. Collectively, ESM possesses antithrombotic activities and offers a basis for the development of a novel anticoagulant.

Topics: Animals; Asarum; Bleeding Time; Blood Coagulation; Blood Coagulation Tests; Cysteine Endopeptidases; Dioxoles; Female; Fibrin; Fibrinolysis; Fibrinolytic Agents; Human Umbilical Vein Endothelial Cells; Humans; Lignans; Mice; Mice, Inbred ICR; Neoplasm Proteins; Plasminogen Activator Inhibitor 1; Platelet Aggregation; Polymerization; Structure-Activity Relationship; Thrombin; Tissue Plasminogen Activator

To study the chemical constituents of Zanthoxyli Cortex.. The chemical constituents were isolated and purified by silica gel and HP-20, MCI gel, Sephadex LH -20 column chromatography, RP-18 and PTLC. Their structures were elucidated by the analysis of spectral data and chemical properties.. Ten compounds were isolated from EtOAc extract and their structures were identified as: asarinin (I), fargesin (II), eudesmin (III), (1R, 2R, 5R, 6S)-2-(3,4-dimethoxyphenyl)-6-(3,4-dihydroxyphenyl)-3,7-dioxabicyclo[3.3.0]-octane(IV), dimethoxysamin(V), rel-(1R,5R,6S)-6-(3,4-dimethoxyphen-yl)-3,7-dioxabicyclo-[3.3.0]-octan-2-one(VI), Magnone A(VII), beta-sitoste-rol( VIII), beta-armyrin(IX), beta-amyrone(X).. These compounds isolated from Zanthoxyli Cortex's Ethyl acetate extract are all known compounds. Fargesin(II) and beta-amyrone(X) are isolated from Zanthoxyli Cortex for the first time.

Topics: Acetates; Benzodioxoles; Dioxoles; Furans; Lignans; Magnetic Resonance Spectroscopy; Plant Bark; Plant Extracts; Rutaceae; Triterpenes

Dietary sesamin (1:1 mixture of sesamin and episesamin) decreases fatty acid synthesis but increases fatty acid oxidation in rat liver. Dietary α-lipoic acid lowers hepatic fatty acid synthesis. These changes can account for the serum lipid-lowering effect of sesamin and α-lipoic acid. It is expected that the combination of these compounds in the diet potentially ameliorates lipid metabolism more than the individual compounds. We therefore studied the combined effect of sesamin and α-lipoic acid on lipid metabolism in rats.. Male Sprague-Dawley rats were fed diets supplemented with 0 or 2 g/kg sesamin and containing 0 or 2.5 g/kg α-lipoic acid for 22 days.. Sesamin and α-lipoic acid decreased serum lipid concentrations and the combination of these compounds further decreased the parameters in an additive fashion. These compounds reduced the hepatic concentration of triacylglycerol, the lignan being less effective in decreasing this value. The combination failed to cause a stronger decrease in hepatic triacylglycerol concentration. The combination of sesamin and α-lipoic acid decreased the activity and mRNA levels of hepatic lipogenic enzymes in an additive fashion. Sesamin strongly increased the parameters of hepatic fatty acid oxidation enzymes. α-Lipoic acid antagonized the stimulating effect of sesamin of fatty acid oxidation through reductions in the activity of some fatty acid oxidation enzymes and carnitine concentration in the liver. This may account for the failure to observe strong reductions in hepatic triacylglycerol concentration in rats given a diet containing both sesamin and α-lipoic acid.

Topics: Animals; Appetite Depressants; Carnitine; Dietary Supplements; Dioxoles; Fatty Acids; Gene Expression Regulation, Enzymologic; Hypolipidemic Agents; Lignans; Lipid Metabolism; Lipogenesis; Lipolysis; Liver; Male; Organ Size; Rats; Rats, Sprague-Dawley; RNA, Messenger; Thioctic Acid; Triglycerides; Weight Gain

Obesity and its associated health risks still demand for effective therapeutic strategies. Drugs and compositions derived from Oriental medicine such as green tea polyphenols attract growing attention. Previously, an extract from the Japanese spice bush Lindera obtusiloba (L. obtusiloba) traditionally used for treatment of inflammation and prevention of liver damage was shown to inhibit adipogenesis. Aiming for the active principle of this extract (+)-episesamin was identified, isolated and applied in adipogenic research using 3T3-L1 (pre)adipocytes, an established cell line for studying adipogenesis. With an IC50 of 10μM (+)-episesamin effectively reduced the growth of 3T3-L1 preadipocytes and decreased hormone-induced 3T3-L1 differentiation as shown by reduced accumulation of intracellular lipid droplets and diminished protein expression of GLUT-4 and vascular endothelial growth factor. Mechanistically, the presence of (+)-episesamin during hormone-induced differentiation provoked a reduced phosphorylation of ERK1/2 and β-catenin along with a reduced protein expression of peroxisome proliferator-activated receptor γ and a strongly increased protein expression of iNOS. Treatment of mature adipocytes with (+)-episesamin resulted in a reduction of intracellular stored lipid droplets and induced the proapoptotic enzymes caspases-3/-7. Besides interfering with adipogenesis, (+)-episesamin showed anti-inflammatory activity by counteracting the lipopolysaccharide- and tumor necrosis factor α-induced secretion of interleukin 6 by 3T3-L1 preadipocytes. In conclusion, (+)-episesamin seems to be the active drug in the L. obtusiloba extract being responsible for the inhibition of adipogenesis and, thus, should be evaluated as a novel potential complementary treatment for obesity.

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Animals; Anti-Inflammatory Agents; beta Catenin; Caspase 3; Caspase 7; Cell Differentiation; Dioxoles; Down-Regulation; Glucose Transporter Type 4; Inflammation; Interleukin-6; Lignans; Lindera; Lipid Metabolism; Liver; Mice; Nitric Oxide Synthase Type II; Obesity; Phosphorylation; Plant Extracts; PPAR gamma; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A; Wnt Signaling Pathway

The effect of chronic administration of sesamin was studied on aortic reactivity of streptozotocin diabetic rats. Male diabetic rats received sesamin for 7 weeks after diabetes induction. Contractile responses to KCl and phenylephrine and relaxation response to acetylcholine were obtained from aortic rings. Maximum contractile response of endothelium-intact rings to phenylephrine was significantly lower in sesamin-treated diabetic rats relative to untreated diabetics and endothelium removal abolished this difference. Meanwhile, endothelium-dependent relaxation to acetylcholine was significantly higher in sesamin-treated diabetic rats as compared to diabetic ones and pretreatment of rings with nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester significantly attenuated the observed response. Two-month diabetes also resulted in an elevation of malondialdehyde and decreased superoxide dismutase activity and sesamin treatment significantly improved these changes. Therefore, chronic treatment of diabetic rats with sesamin could prevent some abnormal changes in vascular reactivity in diabetic rats through nitric oxide and via attenuation of oxidative stress and tissue integrity of endothelium is necessary for its beneficial effect.

Topics: Animals; Aorta; Diabetes Mellitus, Experimental; Dioxoles; Dose-Response Relationship, Drug; In Vitro Techniques; Lignans; Male; Nitric Oxide; Oxidative Stress; Prostaglandins; Rats; Rats, Wistar; Sesamum; Vasoconstriction

In the present study, we investigated the effect of sesamin on CYP1A (7-ethoxyresorufin-O-deethylase, EROD) and CYP2E1-like activities (p-nitrophenol hydroxylase, PNPH) in hepatic microsomes obtained from Atlantic salmon (Salmo salar) and common carp (Cyprinus carpio). Addition of sesamin to the incubations in a concentration range from 1 to 200 μM decreased the activities of EROD and PNPH in a concentration dependent manner. It is likely that the inhibition of EROD was mechanism-based as demonstrated by the decrease in the IC50 value from 5.9 to 3.2 μM for A. salmon and from 7.9 to 3.0 μM for common carp when 5 min pre-incubation step was included. Similarly, PNPH activity was inhibited by sesamin with a decrease in the IC50 values from 61.7 to 15.2 μM for A. salmon and from 194.3 to 20.7 μM for common carp. Thus, our results indicated that sesamin can act as a mechanism-based inhibitor of EROD and PNPH activity with similar degree of inhibition in both fish species. More importantly, the inhibition of CYP1A, in addition to being mechanism-based, was competitive with K(i) value of 5.3 μM.

Topics: Animals; Antioxidants; Carps; Cytochrome P-450 CYP1A1; Cytochrome P-450 CYP2E1 Inhibitors; Dioxoles; Inhibitory Concentration 50; Kinetics; Lignans; Microsomes, Liver; Salmon

Thrombin plays important roles in the pathology of intracerebral hemorrhage (ICH). The recruitment of activated microglia, accompanied by thrombin-induced phosphorylation of the mitogen-activated protein kinase (MAPK) family, contributes to ICH-associated neuron loss. Here we investigated the possibility that sesamin, a lignan of sesame seed oil, is a natural candidate as an inhibitor of microglial activation and MAPK pathways under ICH insults. Sesamin (30-100 μM) suppressed thrombin-induced nitric oxide (NO) production by primary-cultured rat microglia via inhibition of inducible NO synthase (iNOS) protein expression, independently of the antioxidative effect. Sesamin selectively inhibited p44/42 MAPK phosphorylation in the MAPK family (p38 and p44/42) involved in iNOS protein expression in primary-cultured rat microglia. An in vivo rat ICH model was prepared by intrastriatal injection of 0.20U collagenase type IV unilaterally. ICH evoked the phosphorylation of p44/42 MAPK, microglial proliferation with morphological change into the activated ameboid form, and neuron loss. The phosphorylation of p44/42 MAPK was inhibited by intracerebroventricular administration of 30-nmol sesamin. Sesamin prevented ICH-induced increase of microglial cells in the perihematomal area. Notably, ramified microglia, the resting morphology, were observed in brain sections of the animals administrated sesamin. Sesamin furthermore achieved neuroprotection in the perihematomal area but not in the hematomal center. These results suggest that sesamin is a promising natural product as a novel therapeutic strategy based on the regulation of microglial activities accompanied by the activated p44/42 MAPK pathway in ICH.

Topics: Animals; Antioxidants; Brain; Cell Death; Cell Proliferation; Cells, Cultured; Cerebral Hemorrhage; Dioxoles; Disease Models, Animal; Lignans; Male; MAP Kinase Signaling System; Microglia; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Neurons; Neuroprotective Agents; Nitric Oxide; Nitric Oxide Synthase Type II; p38 Mitogen-Activated Protein Kinases; Rats, Sprague-Dawley; Rats, Wistar

This study was designed to evaluate the in vivo cardioprotective effects of food-derived sesamin in spontaneously hypertensive rats (SHR). The study was performed with 17-week-old male normotensive Wistar-Kyoto rats (WKY) and SHR which are untreated or treated with orally administered sesamin for 16 weeks before they were sacrificed. Long-term treatment with sesamin obviously improved left ventricular (LV) hypertrophy and fibrosis in SHR, as indicated by the decrease of LV weight/body weight, myocardial cell size, cardiac fibrosis and collagen type I expression as well as the amelioration of the LV ultrastructure. These effects were associated with reduced systolic blood pressure, enhanced cardiac total antioxidant capability and decreased malondialdehyde content, nitrotyrosine level and transforming growth factor β1 (TGF-β1) expression. All these results suggest that chronic treatment with sesamin improves LV remodeling in SHR through alleviation of oxidative and nitrative stress, reduction of blood pressure and downregulation of TGF-β1 expression.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Collagen Type I; Dioxoles; Disease Models, Animal; Down-Regulation; Fibrosis; Heart; Hypertension; Hypertrophy, Left Ventricular; Lignans; Male; Malondialdehyde; Myocytes, Cardiac; Rats; Rats, Inbred SHR; Rats, Inbred WKY; RNA, Messenger; Transforming Growth Factor beta1; Tyrosine; Ventricular Remodeling

The ability of sesamin from sesame meal to ameliorate insulin resistance in KK-Ay mice (an animal model of type 2 diabetes) was evaluated.. Treatment with sesamin (100 or 50 mg kg(-1)) significantly decreased the level of fasting plasma glucose, glycosylated serum protein, serum insulin, triglycerides, cholesterol, free fatty acid and malondialdehyde content of livers. Treatment with sesamin significantly increased the content of hepatic glycogen, reduced glutathione and the activity of superoxide dismutase and glutathione peroxidase. Moreover, the insulin-binding capacity to liver crude plasma membranes increased and histopathological changes of the pancreas were ameliorated in the treatment group.. Sesamin has hypoglycaemic, hypolipidaemic and the ability to ameliorate insulin resistance in KK-Ay mice, which might be related to its effect on insulin receptors, and thus increases insulin sensitivity.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 2; Dioxoles; Female; Glutathione; Glutathione Peroxidase; Hypoglycemic Agents; Insulin Resistance; Lignans; Lipids; Mice; Mice, Inbred C57BL; Sesamum; Superoxide Dismutase

γ-Tocotrienol and sesamin are phytochemicals that display potent anticancer activity. Since sesamin inhibits the metabolic degradation of tocotrienols, studies were conducted to determine if combined treatment with sesamin potentiates the antiproliferative effects of γ-tocotrienol on neoplastic mouse (+SA) and human (MCF-7 and MDA-MB-231) mammary cancer cells. Results showed that treatment with γ-tocotrienol or sesamin alone induced a significant dose-responsive growth inhibition, whereas combination treatment with these agents synergistically inhibited the growth of +SA, MCF-7 and MDA-MB-231 mammary cancer cells, while similar treatment doses were found to have little or no effect on normal (mouse CL-S1 and human MCF-10A) mammary epithelial cell growth or viability. However, sesamin synergistic enhancement of γ-tocotrienol-induced anticancer effects was not found to be mediated from a reduction in γ-tocotrienol metabolism. Rather, combined treatment with subeffective doses of γ-tocotrienol and sesamin was found to induce G1 cell cycle arrest, and a corresponding decrease in cyclin D1, CDK2, CDK4, CDK6, phospho-Rb, and E2F1 levels, and increase in p27 and p16 levels. Additional studies showed that the antiproliferative effect of combination treatment did not initiate apoptosis or result in a decrease in mammary cancer cell viability. Taken together, these findings indicate that the synergistic antiproliferative action of combined γ-tocotrienol and sesamin treatment in mouse and human mammary cancer cells is cytostatic, not cytotoxic, and results from G1 cell cycle arrest.

Topics: Animals; Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Chromans; Cyclin-Dependent Kinase Inhibitor Proteins; Cyclins; Dioxoles; Drug Synergism; Drug Therapy, Combination; E2F1 Transcription Factor; Female; Gene Expression Regulation, Neoplastic; Humans; Lignans; Mice; Molecular Structure; Retinoblastoma Protein; Vitamin E

Asarinin, C(20)H(18)O(6), was isolated as a racemate from the shrub Zanthoxylum alatum. Both forms of the enantiomerically pure substance, (+)- and (-)-asarinin, have been the subject of a total of five previous structure determinations that are essentially identical except for the absolute stereochemistry. However, there seems to be some confusion in the literature concerning these structure determinations of asarinin and also those of its stereoisomer sesamin. The molecular structure of racemic asarinin differs from that of the pure enantiomers in the orientation of one ring system. In the packing of the racemate, molecules are linked by C-H...O interactions to form ribbons parallel to [101].

Topics: Crystallography, X-Ray; Dioxoles; Drugs, Chinese Herbal; Hydrogen Bonding; Lignans; Molecular Structure; Stereoisomerism; Zanthoxylum

The present study investigated the anti-ageing activity of sesamin and its effect on gene expression of superoxide dismutase (SOD), catalase (CAT), methuselah (Mth) and Rpn11 in Drosophila melanogaster. Results demonstrated that 0.2 % sesamin in diet prolonged the mean lifespan of OR wild fruit flies by 12 %, accompanied by up-regulation of SOD1, SOD2, CAT and Rpn11. Sesamin at 0.2 % in diet also attenuated paraquat-induced neurodegeneration with up-regulation of SOD1, SOD2 and Rpn11 in OR wild fruit flies. Supplementation of 0.2 % sesamin in diet increased the survival time of OR wild type flies and Alzheimer flies Aβ42 33769 when they were challenged with paraquat. Furthermore, sesamin-induced increase in the activity and expression of antioxidant enzymes also suggests that the longevity promoting activity of sesamin are possibly due to its action as a hormetin by inducing oxidative stress response-mediated hormesis. It was concluded that sesamin extended the mean lifespan and alleviated the neurodegeneration in Drosophila melanogaster at least mediated by its interaction with genes SOD1, SOD2, CAT, and Rpn11, but not with gene Mth.

Topics: Animals; Antioxidants; Catalase; Dietary Supplements; Dioxoles; Drosophila; Drosophila Proteins; Endopeptidases; Gene Expression Regulation; Herbicides; Lignans; Longevity; Male; Models, Animal; Paraquat; Superoxide Dismutase

Antioxidative effects of sesamin (a mixture of sesamin and episesamin) were evaluated in the liver, kidney and inferior vena cava of living rats using a radiofrequency ESR method. TEMPOL, 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl, was used as an in vivo redox probe, the half-life of which is believed to be correlated with the antioxidant status. The oral administration of sesamin (250 mg/kg rat weight) 3 h before ESR measurements shortened the half-life of TEMPOL in the liver by 10 - 15% as compared with the controls, but did not affect the other organs. This effect was maintained for at least 3 h after the administration, and then disappeared at 24 h, corresponding to the results of our preliminary pharmacokinetic studies. Changes in the reducing ability were observed only in the hepatic sites of the sesamin-treated rats. These findings suggest that sesamin exhibits effective antioxidant activity in the liver via modulation of the intracellular redox status related to TEMPOL reduction.

Topics: Administration, Oral; Animals; Antioxidants; Cyclic N-Oxides; Dioxoles; Electron Spin Resonance Spectroscopy; Half-Life; Lignans; Liver; Male; Molecular Structure; Oxidation-Reduction; Rats; Rats, Wistar; Spin Labels

Sesamin (Ses), one of the major lignans in sesame seeds and oil, has been reported to have many benefits and medicinal properties. However, its protective effects against nickel (Ni)-induced injury in liver have not been clarified. The aim of the present study was to investigate the effects of sesamin on hepatic oxidative DNA injury and apoptosis in mice exposed to nickel. Kunming mice were exposed to nickel sulfate with or without sesamin coadministration for 20 days. The data showed that sesamin significantly prevented nickel-induced hepatotoxicity in a dose-dependent manner, indicated by both diagnostic indicators of liver damage (serum aminotransferase activities) and histopathological analysis. Moreover, nickel-induced profound elevation of reactive oxygen species (ROS) production and oxidative stress, as evidenced by an increase of the lipid peroxidation level and depletion of the intracellular reduced glutathione (GSH) level in liver, were suppressed by treatment with sesamin. Sesamin also restored the activities of antioxidant enzymes (T-SOD, CAT, and GPx) and decreased 8-hydroxy-2-deoxyguanosine (8-OHdG) levels in nickel-treated mice. Furthermore, a TUNEL assay showed that nickel-induced apoptosis in mouse liver was significantly inhibited by sesamin. Exploration of the underlying mechanisms of sesamin action revealed that activities of caspase-3 were markedly inhibited by the treatment of sesamin in the liver of nickel-treated mice. Sesamin increased expression levels of phosphoinositide-3-kinase (PI3K) and phosphorylated protein kinase B (PBK/Akt) in liver, which in turn inactivated pro-apoptotic signaling events, restoring the balance between pro- and anti-apoptotic Bcl-2 proteins in the liver of nickel-treated mice. In conclusion, these results suggested that the inhibition of nickel-induced apoptosis by sesamin is due at least in part to its antioxidant activity and its ability to modulate the PI3K-Akt signaling pathway.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Alanine Transaminase; Animals; Antioxidants; Apoptosis; Aspartate Aminotransferases; Blotting, Western; Caspase 3; Deoxyguanosine; Dioxoles; DNA Damage; Glutathione; In Situ Nick-End Labeling; Lignans; Lipid Peroxidation; Liver; Male; Mice; Nickel; Oncogene Protein v-akt; Oxidative Stress; Phosphatidylinositol 3-Kinases; Reactive Oxygen Species; Signal Transduction; Thiobarbituric Acid Reactive Substances

Nuclear DNA-binding protein high mobility group box 1 (HMGB1) protein acts as a late mediator of severe vascular inflammatory conditions, such as sepsis and septic shock. Epi-sesamin (ESM), an important component of Asarum sieboldii roots, is known to exhibit anti-allergic, anti-nociceptive, and anti-fungal effects. However, little is known of its effects on HMGB1-mediated inflammatory responses. Here, we investigated this issue by monitoring the effects of ESM on lipopolysaccharide (LPS) or cecal ligation and the puncture (CLP)-mediated release of HMGB1, and on modulation of HMGB1-mediated inflammatory responses. ESM potently inhibited HMGB1 release, down-regulated HMGB1-dependent inflammatory responses in human endothelial cells, and inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with ESM resulted in reduced CLP-induced release of HMGB1 and sepsis-related mortality. Of particular interest, ESM inhibition of HMGB1-mediated anti-inflammatory activity was more potent than that by sesamin (SM), likely due to differences between their three-dimensional structures. These results indicate that ESM could be a candidate therapeutic agent for treatment of various severe vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway.

Topics: Animals; Capillary Permeability; Cell Adhesion; Cell Survival; Dioxoles; HMGB1 Protein; Human Umbilical Vein Endothelial Cells; Humans; Lignans; Male; Mice; Mice, Inbred C57BL; Sesame Oil; Vasculitis

Sesamin, a major sesame seed lignan, has diverse biological functions including the modulation of molecular actions in lipid metabolic pathways and reducing cholesterol levels. Vertebrates have different capacities to biosynthesize long-chain PUFA from dietary precursors and sesamin can enhance the biosynthesis of ALA to EPA and DHA in marine teleost. Early juvenile barramundi, Lates calcarifer, were fed for two weeks on diets rich in ALA or SDA derived from linseed or Echium plantagineum, respectively. Both diets contained phytosterols and less cholesterol compared with a standard fish oil-based diet. The growth rates were reduced in the animals receiving sesamin regardless of the dietary oil. However, the relative levels of n-3 LC-PUFA in total lipid, but not the phospholipid, increased in the whole body by up to 25% in animals fed on sesamin with ALA or SDA. Sesamin reduced the relative levels of triacylglycerols and increased polar lipid, and did not affect the relative composition of phospholipid subclasses or sterols. Sesamin is a potent modulator for LC-PUFA biosynthesis in animals, but probably will have more effective impact at advanced ages. By modulating certain lipid metabolic pathways, sesamin has probably disrupted the body growth and development of organs and tissues in early juvenile barramundi.

Topics: Animal Feed; Animals; Dietary Fats, Unsaturated; Dioxoles; Fatty Acids; Lignans; Lipid Metabolism; Lipids; Perciformes

The protective effect of sesamin (SES) from sesame meal on NIT-1 pancreatic β-cells damaged by streptozotocin (STZ) in vitro was investigated. The cell viability, insulin secretion, the activity of superoxide dismutase(SOD), glutathione peroxidase (GSHpx) and the content of reduced glutathione (GSH) increased significantly when incubated with SES (400, 200 µg mL-1). The content of malondialdehyde (MDA), nitric oxide (NO) production, and the activity of NO synthase (NOS), inducible NOS (iNOS), decreased significantly when incubated with SES. The destructive changes of NIT-1 cells were ameliorated when treated with SES under microscopic observation. These data suggested that SES had obvious protective effect on NIT-1 pancreatic β-cells damaged by STZ, which might be related to its effects of decreasing levels of β-cell-destroying factors such as oxidative stress and NO synthesis.

Topics: Animals; Antibiotics, Antineoplastic; Antioxidants; Cell Line; Cell Survival; Dioxoles; Glutathione; Glutathione Peroxidase; Insulin-Secreting Cells; Lignans; Mice; Streptozocin; Superoxide Dismutase

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Treatment options, especially in advanced tumor stages, are still limited. Inhibition of signaling cascades involved in the pathogenesis of HCC - such as NF-ĸB - offer a promising therapeutic approach. Aim of this study was to examine anti-neoplastic effects of (+)-episesamin which has been isolated from an anti-fibrotic extract of Lindera obtusiloba on human HCC cells with particular interest in activation of NF-κB. The human HCC cell lines HepG2, Huh-7 and SK-Hep1 were treated with (+)-episesamin. Beside measurement of proliferation, invasion and apoptosis, effects of (+)-episesamin on NF-κB-activity, VEGF secretion and enzymatic MMP-9 activity were determined. Anti-inflammatory effects were assessed by IL-6 ELISA using HCC cells and RAW264.7 macrophages. 10 μM (+)-episesamin reduced the proliferation of HCC cells by ~50%, suppressed invasion and induced apoptosis. DNA-binding ELISA experiments revealed that (+)-episesamin treated HCC cells showed a suppressed basal and TNFα-induced activation of NF-κB and a subsequent suppression of TNFα- and LPS-induced IL-6 production. Further, (+)-episesamin exhibited inhibitory effects on the enzymatic activity of recombinant MMP-9 and the secretion of MMP-9 and VEGF by HCC cells into their supernatants. Our findings show that anti-neoplastic effects of (+)-episesamin are mediated via suppressed activation of NF-κB which entails a decreased release of pro-inflammatory IL-6. In addition, (+)-episesamin inhibits MMP-9, which is strongly expressed in invasive HCC, and the production of proangiogenic VEGF. We conclude that (+)-episesamin has the potential to be further explored as a complementary treatment for HCC.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Apoptosis; Carcinoma, Hepatocellular; Cell Line; Cell Line, Tumor; Cell Proliferation; Dioxoles; Humans; Interleukin-6; Lignans; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Mice; Neoplasm Invasiveness; NF-kappa B; Vascular Endothelial Growth Factor A

Flaxseed (FS) has a breast tumor-reducing effect, possibly because of its high content of secoisolariciresinol diglucoside (SDG) lignan. Sesame seed (SS) is rich in the lignan sesamin (SES) but is non-protective. Both lignans are metabolized to estrogen-like enterodiol and enterolactone. The objective of this study was to differentiate the effects of SDG and SES on established human estrogen receptor-positive breast tumors (MCF-7) in athymic mice with high serum estrogen to help explain the different effects of FS and SS. Mice were fed for 8 wk the basal diet (BD, control) or BD supplemented with 1 g/kg SDG or SES. SES reduced palpable tumor size by 23% compared to control, whereas SDG did not differ from SES or control. Both treatments reduced tumor cell proliferation, but only SES increased apoptosis. SDG and SES reduced human epidermal growth factor receptor 2 and endothelial growth factor receptor expressions, but only SES reduced downstream pMAPK. Neither treatment affected IGF-1R, vascular endothelial growth factor receptor-2, Akt, pAkt, or MAPK of the growth factor signaling pathway. Thus, at high serum estrogen levels, SDG may not account for the tumor reducing effect of FS. SES was more effective than SDG in reducing breast tumor growth, but its effect may have been lost when consumed as a component of SS.

Topics: Animals; Apoptosis; Body Weight; Breast Neoplasms; Butylene Glycols; Cell Line, Tumor; Cell Proliferation; Dioxoles; Eating; Estrogens; Female; Flax; Glucosides; Humans; Lignans; Mice; Mice, Nude; Receptor, ErbB-2; Receptor, IGF Type 1; Receptors, Estrogen; Seeds; Sesamum; Signal Transduction; Vascular Endothelial Growth Factor Receptor-2; Xenograft Model Antitumor Assays

The effects of sesamin on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells were investigated. Sesamin at concentration ranges of 20-75 μM exhibited a significant increase in intracellular dopamine levels at 24 h: 50 μM sesamin increased dopamine levels to 133% and tyrosine hydroxylase (TH) activity to 128.2% of control levels. Sesamin at 20-100 μM rapidly increased the intracellular levels of cyclic AMP (cAMP) to 158.3%-270.3% of control levels at 30 min. At 50 μM, sesamin combined with L-DOPA (50, 100 and 200 μM) further increased the intracellular dopamine levels for 24 h compared to L-DOPA alone. In the absence or presence of L-DOPA (100 and 200 μM), sesamin (50 μM) increased the phosphorylation of TH, cAMP-dependent protein kinase (PKA), and cAMP-response element-binding protein (CREB), as well as the mRNA levels of TH and CREB for 24 h, an effect which was reduced by L-DOPA (100 and 200 μM). In addition, 50 μM sesamin exhibited a protective effect against L-DOPA (100 and 200 μM)-induced cytotoxicity via the inhibition of reactive oxygen species (ROS) production and superoxide dismutase reduction, induction of extracellular signal-regulated kinase (ERK)1/2 and BadSer112 phosphorylation and Bcl-2 expression, and inhibition of cleaved-caspase-3 formation. These results suggested that sesamin enhanced dopamine biosynthesis and L-DOPA-induced increase in dopamine levels by inducing TH activity and TH gene expression, which was mediated by cAMP-PKA-CREB systems. Sesamin also protected against L-DOPA (100-200 μM)-induced cytotoxicity through the suppression of ROS activity via the modulation of ERK1/2, BadSer112, Bcl-2, and caspase-3 pathways in PC12 cells. Therefore, sesamin might serve as an adjuvant phytonutrient for neurodegenerative diseases.

Topics: Animals; Cell Survival; Cytotoxins; Dioxoles; Dopamine; Dose-Response Relationship, Drug; Levodopa; Lignans; PC12 Cells; Rats; Reactive Oxygen Species; Seeds; Sesamum

Metabolic transformations of two substrates for human cytochrome P450 (CYP450) 2C9, tolbutamide and diclofenac, were investigated in hepatic microsomes from Atlantic salmon (Salmo salar L.). Tolbutamide hydroxylation followed Michaelis-Menten kinetics. Mean apparent Michaelis-Menten constant (K(m)) and maximum reaction velocity (V(max)) values for 4-hydroxytolbutamide (TBOH) formation were 0.09 ± 0.031 mM and 49.5 ± 6.03 pmol/min/mg, respectively. Addition of sulfaphenazole, an inhibitor for mammalian CYP2C9, in a range from 1 to 200 μM decreased formation of TBOH in a concentration-dependent manner, but not to 50%. Neither fluconazole, an inhibitor of human CYP2C9, nor ketoconazole, inhibitor of CYP1A and CYP3A in fish, affected TBOH formation. In contrast ellipticine, an inhibitor of CYP1A in fish inhibited TBOH formation with the IC(50) value of 12.1 μM. The rate of TBOH formation was competitively inhibited by 100 μM of sesamin in the incubations, but the degree of inhibition did not increase with increased sesamin concentration. Ethoxyresorufin hydroxylase (EROD) activity was inhibited by tolbutamide in a non-competitive manner (inhibition constant K(i) = 218 μM). Our data suggest that tolbutamide is metabolized by salmon microsomes with formation of TBOH. CYP1A might be involved in this reaction as suggested by decreased TBOH formation in the presence of ellipticine and decreased EROD activity in the presence of tolbutamide. Incubation of diclofenac with the microsomes yielded no metabolite formation, suggesting that salmon does not possess diclofenac-metabolizing activity.

Topics: Animals; Aryl Hydrocarbon Hydroxylases; Biotransformation; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Diclofenac; Dioxoles; Ellipticines; Fish Proteins; Fluconazole; Hydroxylation; Ketoconazole; Kinetics; Lignans; Microsomes, Liver; Oxazines; Salmo salar; Sulfaphenazole; Tolbutamide

In the present study, we aimed to evaluate the protective effect of sesamin on kidney damage and renal endothelial dysfunction in two-kidney, one-clip renovascular hypertensive rats fed with a high-fat-sucrose diet (2K1C rats on HFS diet). Sesamin was intragastrically administered to 2K1C rats on HFS diet for eight weeks. Then, we measured the levels of serum hydrogen peroxide (H₂O₂), total antioxidant capability (T-AOC), renal malonaldehyde (MDA), total-erythrocuprein (T-SOD) and glutathione peroxidase (GSH-P(X)). The expressions of endothelial nitric oxide synthase (eNOS), nitrotyrosine and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit p47(phox) in the left and right renal cortexes were detected by Western blotting. Pathological changes in the left and right renal cortexes were observed by periodic acid-schiff staining (PAS) and Masson's staining. Treatment with sesamin (120 and 60mg/kg⁻¹·d⁻¹) in 2K1C rats on HFS diet improved renal function, corrected structural abnormalities, and attenuated renal oxidative stress. Furthermore, sesamin increased eNOS protein expression and reduced nitrotyrosine and p47phox protein expression. These results demonstrated that long-term treatment with sesamin had renoprotective effect and improved renal endothelial dysfunction via upregulation of eNOS expression and reduction of NO oxidative inactivation in both clipped and contralateral kidneys of 2K1C rats on HFS diet, and sesamin may have a favorably therapeutic value in treating chronic kidney disease in patients with hypertension and hyperlipemia.

Topics: Animals; Antihypertensive Agents; Antioxidants; Diet, High-Fat; Dietary Sucrose; Dioxoles; Dose-Response Relationship, Drug; Down-Regulation; Endothelium, Vascular; Hypertension, Renovascular; Hypolipidemic Agents; Kidney; Kidney Cortex; Lignans; Male; NADPH Oxidases; Nitric Oxide; Nitric Oxide Synthase Type III; Random Allocation; Rats; Rats, Sprague-Dawley; Tyrosine; Up-Regulation

Interrelated effects of dihomo-γ-linolenic acid (DGLA) and arachidonic acid (ARA), and sesamin, a sesame lignan, on hepatic fatty acid synthesis and oxidation were examined in rats. Rats were fed experimental diets supplemented with 0 or 2 g/kg sesamin (1:1 mixture of sesamin and episesamin), containing 100 g/kg of maize oil or fungal oil rich in DGLA or ARA for 16 d. Among the groups fed sesamin-free diets, oils rich in DGLA or ARA, especially the latter, compared with maize oil strongly reduced the activity and mRNA levels of various lipogenic enzymes. Sesamin, irrespective of the type of fat, reduced the parameters of lipogenic enzymes except for malic enzyme. The type of dietary fat was rather irrelevant in affecting hepatic fatty acid oxidation among rats fed the sesamin-free diets. Sesamin increased the activities of enzymes involved in fatty acid oxidation in all groups of rats given different fats. The extent of the increase depended on the dietary fat type, and the values became much higher with a diet containing sesamin and oil rich in ARA in combination than with a diet containing lignan and maize oil. Analyses of mRNA levels revealed that the combination of sesamin and oil rich in ARA compared with the combination of lignan and maize oil markedly increased the gene expression of various peroxisomal fatty acid oxidation enzymes but not mitochondrial enzymes. The enhancement of sesamin action on hepatic fatty acid oxidation was also confirmed with oil rich in DGLA but to a lesser extent.

Topics: 8,11,14-Eicosatrienoic Acid; Animals; Arachidonic Acid; Cell Extracts; Corn Oil; Dioxoles; Fatty Acids; Fungi; Gene Expression Regulation, Enzymologic; Hypolipidemic Agents; Lignans; Lipids; Lipogenesis; Lipolysis; Liver; Male; Oxidation-Reduction; Peroxisomes; Rats; Rats, Sprague-Dawley; RNA, Messenger

This study is to observe anti-lipotoxic effect of sesamin on renovascular hypertensive rats fed with a high-fat, high-sucrose diet. Thirty-four complex model rats were induced by two-kidney, one-clip method and on high-fat and refined-carbohydrate diet for thirteen weeks. From the fifth week, intragastric administration of sesamin (120, 60 and 30 mg x kg(-1) x d(-1)) lasted for eight weeks. Blood pressure (BP), blood fat (BF), blood glucose (BG), free fatty acids (FFA), insulin (Ins), tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 were determined. Pathological changes of pancreas, perirenal fat and liver were semiquantitatively analyzed. In sesamin (120 and 60 mg x kg(-1) x d(-1)) group, it was found that there were decrease of levels of BP, BF, BG, TNF-alpha, IL-6 and FFA, improvement of insulin resistance and glucose tolerance, alleviation of body weight, humid weight of fat, liver and pancreas and their organ index, and reduction of islet cell hyperplasia and amount of lipid droplet vacuoles in lipocyte and hepatocyte. It is implied that sesamin had anti-lipotoxic effect and its mechanism may be closely associated with the amelioration of insulin resistance via reducing lipidoses in hepatocyte and inflammatory adipokines such as TNF-alpha and IL-6.

Topics: Adipocytes; Animals; Anticholesteremic Agents; Antihypertensive Agents; Blood Glucose; Blood Pressure; Body Weight; Cholesterol; Diet, High-Fat; Dioxoles; Dose-Response Relationship, Drug; Fatty Acids, Nonesterified; Glucose Tolerance Test; Hypertension, Renovascular; Insulin; Insulin Resistance; Interleukin-6; Islets of Langerhans; Lignans; Liver; Male; Pancreas; Rats; Rats, Sprague-Dawley; Sucrose; Triglycerides; Tumor Necrosis Factor-alpha

Complications of diabetes are now well-known to affect sensory, motor, and autonomic nerves. Diabetes is also thought to be involved in neurodegenerative processes characteristic of several neurodegenerative diseases. Indeed, it has been acknowledged recently that hyperglycemia-induced oxidative stress contributes to numerous cellular reactions typical of central nervous system deterioration. The goal of the present study was to evaluate the effects of the polyphenol quercetin and the lignan sesamin on high-glucose (HG)-induced oxidative damage in an in vitro model of dopaminergic neurons, neuronal PC12 cells. When incubated with HG (13.5 mg/mL), neuronal PC12 cells showed a significant increase of cellular death. Our results revealed that quercetin and sesamin defend neuronal PC12 cells from HG-induced cellular demise. An elevated level of reactive oxygen and nitrogen species is a consequence of improved oxidative stress after HG administration, and we demonstrated that this production diminishes with quercetin and sesamin treatment. We also found that quercetin and sesamin elicited an increment of superoxide dismutase activity. DNA fragmentation, Bax/Bcl-2 ratio, nuclear translocation of apoptosis-inducing factor, as well as poly(adenosine diphosphate [ADP]-ribose) polymerase cleavage were significantly reduced by quercetin and sesamin administration, affirming their antiapoptotic features. Also, HG treatment impacted caspase-3 cleavage, supporting caspase-3-dependent pathways as mechanisms of apoptotic death. Our results indicate a powerful role for these natural dietary compounds and emphasize preventive or complementary nutritional strategies for diabetes control.

Topics: Animals; Apoptosis; Apoptosis Inducing Factor; Caspase 3; Cytoprotection; Dioxoles; Enzyme Activation; Fluorescent Antibody Technique; Free Radicals; Glucose; Lignans; Neurons; Nitrosation; Oxidation-Reduction; PC12 Cells; Poly(ADP-ribose) Polymerases; Protective Agents; Quercetin; Rats; Stress, Physiological; Superoxide Dismutase

Osteoporosis is a worldwide health problem predominantly affecting post-menopausal women. Therapies aimed at increasing bone mass in osteoporetic patients lag behind comparable investigation of therapeutic strategies focusing on the bone resorption process. Sesamin, a major lignan compound found in Sesamun indicum Linn., has a variety of pharmacological effects, though its activity on bone cell function is unclear. Herein we examine the effect of this lignan on osteoblast differentiation and function.. Cell cytotoxicity and proliferative in hFOB1.19 were examined by MTT and alamar blue assay up to 96 h of treatment. Gene expression of COL1, ALP, BMP-2, Runx2, OC, RANKL and OPG were detected after 24 h of sesamin treatment. ALP activity was measured at day 7, 14 and 21 of cultured. For mineralized assay, ADSCs were cultured in the presence of osteogenic media supplement with or without sesamin for 21 days and then stained with Alizarin Red S. MAPK signaling pathway activation was observed by using western blotting.. Sesamin promoted the gene expression of COL1, ALP, OCN, BMP-2 and Runx2 in hFOB1.19. On the other hand, sesamin was able to up-regulate OPG and down-regulate RANKL gene expression. ALP activity also significantly increased after sesamin treatment. Interestingly, sesamin induced formation of mineralized nodules in adipose derived stem cells (ADSCs) as observed by Alizarin Red S staining; this implies that sesamin has anabolic effects both on progenitor and committed cell stages of osteoblasts. Western blotting data showed that sesamin activated phosphorylation of p38 and ERK1/2 in hFOB1.19.. The data suggest that sesamin has the ability to trigger osteoblast differentiation by activation of the p38 and ERK MAPK signaling pathway and possibly indirectly regulate osteoclast development via the expression of OPG and RANKL in osteoblasts. Therefore, sesamin may be a promising phytochemical that could be developed for supplementation of osteoporotic therapy.

Topics: Cell Differentiation; Dioxoles; Female; Gene Expression; Humans; Lignans; MAP Kinase Signaling System; Osteoblasts; Osteoporosis; p38 Mitogen-Activated Protein Kinases; Sesamum; Up-Regulation

Episesamin is an isomer of sesamin, resulting from the refining process of non-roasted sesame seed oil. Episesamin has two methylendioxyphenyl groups on exo and endo faces of the bicyclic skeleton. The side methylendioxyphenyl group was metabolized by cytochrome-P450. Seven metabolites of episesamin were found in rat bile after treatment with glucuronidase/arylsulfatase and were identified using NMR and MS. The seven metabolites were (7α,7'β,8α,8'α)-3,4-dihydroxy-3',4'-methylenedioxy-7,9':7',9-diepoxylignane (EC-1-1), (7α,7'β,8α,8'α)-3,4-methylenedioxy-3',4'-dihydroxy-7,9':7',9-diepoxylignane (EC-1-2) and (7α,7'β,8α,8'α)-3,4:3',4'-bis(dihydroxy)-7,9':7',9-diepoxylignane (EC-2), (7α,7'β,8α,8'α)-3-methoxy-4-hydroxy-3',4'-methylenedioxy-7,9':7',9-diepoxylignane (EC-1m-1), (7α,7'β,8α,8'α)-3,4-methylenedioxy-3'-methoxy-4'-hydroxy-7,9':7',9-diepoxylignane (EC-1m-2), (7α,7'β,8α,8'α)-3-methoxy-4-hydroxy-3',4'-dihydroxy-7,9':7',9-diepoxylignane (EC-2m-1) and (7α,7'β,8α,8'α)-3,4-dihydroxy-3'-methoxy-4'-hydroxy-7,9':7',9-diepoxylignane (EC-2m-2). EC-1-1, EC-1-2 and EC-2 were also identified as metabolites of episesamin in human liver microsomes. These results suggested that similar metabolic pathways of episesamin could be proposed in rats and humans.

Topics: Animals; Bile; Biological Availability; Cytochrome P-450 Enzyme System; Dioxoles; Humans; Isomerism; Lignans; Microsomes, Liver; Plant Extracts; Rats; Rats, Sprague-Dawley; Seeds; Sesame Oil; Sesamum

Osteoarthritis (OA) is a major disability of elderly people. Sesamin is the main compound in Sesamun indicum Linn., and it has an anti-inflammatory effect by specifically inhibiting Δ5-desaturase in polyunsaturated fatty acid biosynthesis. The chondroprotective effects of sesamin were thus studied in a porcine cartilage explant induced with interleukin-1beta (IL-1β) and in a papain-induced osteoarthritis rat model. With the porcine cartilage explant, IL-1β induced release of sulfated-glycosaminoglycan (s-GAG) and hydroxyproline release, and this induction was significantly inhibited by sesamin. This ability to inhibit these processes might be due to its ability to decrease expression of MMP-1, -3 and -13, which can degrade both PGs and type II collagen, both at the mRNA and protein levels. Interestingly, activation of MMP-3 might also be inhibited by sesamin. Moreover, in human articular chondrocytes (HACs), some pathways of IL-1β signal transduction were inhibited by sesamin: p38 and JNK. In the papain-induced OA rat model, sesamin treatment reversed the following pathological changes in OA cartilage: reduced disorganization of chondrocytes in cartilage, increased cartilage thickness, and decreased type II collagen and PGs loss. Sesamin alone might increase formation of type II collagen and PGs in the cartilage tissue of control rats. These results demonstrate that sesamin efficiently suppressed the pathological processes in an OA model. Thus, sesamin could be a potential therapeutic strategy for treatment of OA.

Topics: Animals; Anti-Inflammatory Agents; Cartilage; Chondrocytes; Collagen Type II; Dioxoles; Dose-Response Relationship, Drug; Gene Expression Regulation, Enzymologic; Glycosaminoglycans; Humans; Hydroxyproline; Interleukin-1beta; JNK Mitogen-Activated Protein Kinases; Lignans; MAP Kinase Signaling System; Matrix Metalloproteinases; Osteoarthritis; p38 Mitogen-Activated Protein Kinases; Papain; Phosphorylation; Proteoglycans; Rats; Swine

Sesamin and episesamin are two epimeric lignans that are found in refined sesame oil. Commercially available sesamin supplements contain both sesamin and episesamin at an approximate 1:1 ratio. Our previous study clarified the sequential metabolism of sesamin by cytochrome P450 (P450) and UDP-glucuronosyltransferase in human liver. In addition, we revealed that sesamin caused a mechanism-based inhibition (MBI) of CYP2C9, the P450 enzyme responsible for sesamin monocatecholization. In the present study, we compared the metabolism and the MBI of episesamin with those of sesamin. Episesamin was first metabolized to the two epimers of monocatechol, S- and R-monocatechols in human liver microsomes. The P450 enzymes responsible for S- and R-monocatechol formation were CYP2C9 and CYP1A2, respectively. The contribution of CYP2C9 was much larger than that of CYP1A2 in sesamin metabolism, whereas the contribution of CYP2C9 was almost equal to that of CYP1A2 in episesamin metabolism. Docking of episesamin to the active site of CYP1A2 explained the stereoselectivity in CYP1A2-dependent episesamin monocatecholization. Similar to sesamin, the episesamin S- and R-monocatechols were further metabolized to dicatechol, glucuronide, and methylate metabolites in human liver; however, the contribution of each reaction was significantly different between sesamin and episesamin. The liver microsomes from CYP2C19 ultra-rapid metabolizers showed a significant amount of episesamin dicatechol. In this study, we have revealed significantly different metabolism by P450, UDP-glucuronosyltransferase, and catechol-O-methyltransferase for sesamin and episesamin, resulting in different biological effects.

Topics: Animals; Aryl Hydrocarbon Hydroxylases; Biotransformation; Catechol O-Methyltransferase; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C9; Dioxoles; Enzyme Inhibitors; Glucuronosyltransferase; Humans; Kinetics; Lignans; Liver; Male; Microsomes, Liver; Molecular Docking Simulation; Molecular Structure; Protein Conformation; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Substrate Specificity

This study examined the effects of sesamin inclusion in vegetable oil-based diets fed to Atlantic salmon (Salmo salar L.). The diets used differed in n-6/n-3 fatty acid (FA) ratio (0.5 and 1) and sesamin content (high 5.8 g/kg, low 1.16 g/kg and no sesamin). The oils used in the feeds were a mixture of rapeseed, linseed and palm oil. Fish were fed for 4 months. Fatty acids and expression of hepatic genes involved in transcription, lipid uptake, desaturation, elongation and β-oxidation were measured. No major effects on the percentage of DHA in white muscle, liver triacylglycerol and phospholipid fraction were detected. Genes involved in β-oxidation, elongation and desaturation were affected by sesamin addition. Limited effects were seen on any of the transcription factors tested and no effect was seen on the expression of peroxisome proliferator-activated receptors (PPAR). Expression of both SREBP-1 and SREBP-2 increased with sesamin addition. It was concluded that supplementation of fish feed with a high level of sesamin had a negative effect on the growth rate and live weight and did not alter the proportions of DHA in tissues even though gene expression was affected. Thus, more studies are needed to formulate a diet that would increase the percentage of DHA in fish without negative effects on fish growth.

Topics: Animals; Diet; Dietary Supplements; Dioxoles; Fatty Acids; Gene Expression Regulation; Lignans; Salmon

Vitamin E isoforms are essential nutrients that are widely used as dietary supplements and therapeutic agents for a variety of diseases. However, their pharmacokinetic (PK) properties remain poorly characterized, and high dosage animal studies may provide further information on their in vivo functions and pharmacological effects. In this study, alpha-tocopherol (α-toc) and delta-tocopherol (δ-toc) levels were measured in mouse plasma and tissues following their high dosage dietary supplementation. Average α-toc levels at 5, 10 and 20 g α-toc/kg diet increased over baseline levels 6-fold in plasma, 1.6-fold in brain, and 4.9-fold in liver. These elevated α-toc concentrations remained constant from 5 to 20 g α-toc/kg diet, rather than showing further increases across these dosages. No α-toc-related toxicity occurred at these high dosages, and strain-specific differences in liver and brain α-toc levels between Balb/cJ and C57Bl/6J mice were observed. Relatively high-dosage administration of dietary δ-toc for 1 or 4 weeks resulted in 6-30-fold increases in plasma and liver levels between dosages of 0.33 and 1.67 g δ-toc/kg diet. Co-administration of sesamin with δ-toc further increased δ-toc levels between 1.3- and 14-fold in plasma, liver, and brain. These results provide valuable PK information on high dosage α-toc and δ-toc in mouse and show that supplementation of sesamin with δ-toc further increases δ-toc levels over those seen with δ-toc supplementation alone.

Topics: Adipose Tissue; alpha-Tocopherol; Animals; Antioxidants; Brain Chemistry; Dietary Supplements; Dioxoles; Lignans; Liver; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Tocopherols; Vitamin E; Vitamin E Deficiency; Vitamins

A growing body of evidence indicates that the majority of Parkinson's disease (PD) cases are associated with microglia activation with resultant elevation of various inflammatory mediators and neuroinflammation. In this study, we investigated the effects of 2 natural molecules, quercetin and sesamin, on neuroinflammation induced by the Parkinsonian toxin 1-methyl-4-phenylpyridinium (MPP(+)) in a glial-neuronal system. We first established that quercetin and sesamin defend microglial cells against MPP(+)-induced increases in the mRNA or protein levels of 3 pro-inflammatory cytokines (interleukin-6, IL-1β and tumor necrosis factor-alpha), as revealed by real time-quantitative polymerase chain reaction and enzyme-linked immunoabsorbent assay, respectively. Quercetin and sesamin also decrease MPP(+)-induced oxidative stress in microglial cells by reducing inducible nitric oxide synthase protein expression as well as mitochondrial superoxide radicals. We then measured neuronal cell death and apoptosis after MPP(+) activation of microglia, in a microglial (N9)-neuronal (PC12) coculture system. Our results revealed that quercetin and sesamin rescued neuronal PC12 cells from apoptotic death induced by MPP(+) activation of microglial cells. Altogether, our data demonstrate that the phytoestrogen quercetin and the lignan sesamin diminish MPP(+)-evoked microglial activation and suggest that both these molecules may be regarded as potent, natural, anti-inflammatory compounds.

Topics: 1-Methyl-4-phenylpyridinium; Animals; Apoptosis; Coculture Techniques; Cytokines; Cytoprotection; Dioxoles; Dopaminergic Neurons; Gene Expression Regulation; Inflammation; Kinetics; Lignans; Mice; Microglia; Mitochondria; Neurons; Neuroprotective Agents; Nitric Oxide Synthase Type II; Oxidative Stress; PC12 Cells; Quercetin; Rats; RNA, Messenger; Superoxides

Epidemiological studies have highlighted the ability of phytochemicals to reduce the risk of breast cancer by attenuating specific intracellular signaling pathways that regulate cell proliferation and survival. γ-Tocotrienol is a natural form of vitamin E that displays potent anticancer activity at doses that have no discernible toxicity toward normal cells. Sesamin is an abundant phytochemical found in sesame seed oil that also shows antiproliferative and antiangiogenic activity against human breast cancer cells. In this study, the combined treatment of subeffective doses of γ-tocotrienol and sesamin caused a synergistic inhibition of murine +SA mammary epithelial cell growth, as determined by the MTT assay and immunofluorescent Ki-67 staining. Western blot studies revealed that combined low-dose treatment of γ-tocotrienol and sesamin caused a marked reduction in EGF-induced ErbB3 and ErbB4 receptors phosphorylation (activation) and a relatively large decrease in intracellular levels of total and/or phosphorylated c-Raf, MEK1/2, ERK1/2, PI3K, PDK1, Akt, p-NFκB, Jak1, Jak2, and Stat1, as compared to cells treated with only one compound or in the vehicle-treated control group. These findings demonstrate that the synergistic growth inhibitory effects of γ-tocotrienol and sesamin treatment are associated with suppression of EGF-dependent mitogenic signaling in mammary tumor cells and suggest that dietary supplementation with these phytochemicals may provide some benefits in the prevention and/or treatment of breast cancer.

Topics: Animals; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Cell Count; Cell Line, Tumor; Cell Survival; Chromans; Dioxoles; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Drug Synergism; Female; Lignans; MAP Kinase Signaling System; Mice; Mice, Inbred BALB C; Microscopy, Confocal; Phosphatidylinositol 3-Kinases; Phosphorylation; Proto-Oncogene Proteins c-raf; Receptor, ErbB-3; STAT1 Transcription Factor; Vitamin E

Sesamin is a sesame component with antihypertensive and antioxidative activities and has recently aroused much interest in studying its potential anticancer application. Macrophage is one of the infiltrating inflammatory cells in solid tumor and may promote tumor progression via enhancement of tumor angiogenesis. In this study, we investigated whether sesamin inhibited macrophage-enhanced proangiogenic activity of breast cancer cell lines MCF-7 and MDA-MB-231. Using vascular endothelial cell capillary tube and network formation assays, both breast cancer cell lines exhibited elevated proangiogenic activities after coculture with macrophages or pretreatment with macrophage-conditioned medium. This elevation of proangiogenic activity was drastically suppressed by sesamin. Vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) induced by macrophages in both cell lines were also inhibited by sesamin. Nuclear levels of HIF-1α and NF-κB, important transcription factors for VEGF and MMP-9 expression, respectively, were obviously reduced by sesamin. VEGF induction by macrophage in MCF-7 cells was shown to be via ERK, JNK, phosphatidylinositol 3-kinase, and NF-κB-mediated pathways. These signaling molecules and additional p38(MAPK) were also involved in macrophage-induced MMP-9 expression. Despite such diverse pathways were induced by macrophage, only Akt and p38(MAPK) activities were potently inhibited by sesamin. Expression of interleukin (IL)-6, IL-8, and tumor necrosis factor-α were substantially increased and involved in macrophage-induced VEGF and MMP-9 mRNA expression in MCF-7 cells. Sesamin effectively inhibited the expression of these cytokines to avoid the reinforced induction of VEGF and MMP-9. In conclusion, sesamin potently inhibited macrophage-enhanced proangiogenic activity of breast cancer cells via inhibition of VEGF and MMP-9 induction.

Topics: Antineoplastic Agents, Phytogenic; Base Sequence; Breast Neoplasms; Cell Line, Tumor; Culture Media, Conditioned; Dioxoles; Female; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Interleukin-6; Interleukin-8; Lignans; Macrophages; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Neovascularization, Pathologic; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Proto-Oncogene Proteins c-akt; RNA, Messenger; RNA, Neoplasm; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

Sesamin is a major lignan that is present in sesame seeds and oil. Sesamin is partially converted to its stereoisomer, episesamin, during the refining process of non-roasted sesame seed oil. We evaluated the genotoxicity of these substances through the following tests: a bacterial reverse mutation assay (Ames test), a chromosomal aberration test in cultured Chinese hamster lung cells (CHL/IU), a bone marrow micronucleus (MN) test in Crlj:CD1 (ICR) mice, and a comet assay using the liver of Sprague-Dawley (SD) rats. Episesamin showed negative results in the Ames test with and without S9 mix, in the in vitro chromosomal aberration test with and without S9 mix, and in the in vivo comet assay. Sesamin showed negative results in the Ames test with and without S9 mix. In the in vitro chromosomal aberration test, sesamin did not induce chromosomal aberrations in the absence of S9 mix, but induced structural abnormalities at cytotoxic concentrations in the presence of S9 mix. Oral administration of sesamin at doses up to 2.0g/kg did not cause a significant increase in either the percentage of micronucleated polychromatic erythrocytes in the in vivo bone marrow MN test or in the % DNA in the comet tails in the in vivo comet assay of liver cells. These findings indicate that sesamin does not damage DNA in vivo and that sesamin and episesamin have no genotoxic activity.

Topics: Animals; Bone Marrow Cells; Cells, Cultured; Chromosome Aberrations; Comet Assay; Cricetinae; Cricetulus; Dioxoles; DNA Damage; Dose-Response Relationship, Drug; Erythrocytes; Lignans; Liver Extracts; Male; Mice; Mice, Inbred ICR; Micronucleus Tests; Microsomes, Liver; Molecular Structure; Mutagenicity Tests; Mutation; Rats; Rats, Sprague-Dawley; Salmonella typhimurium; Sesame Oil

The effects of inclusion of sesamin / episesamin in Baltic Atlantic salmon (Salmo salar L.) diets based on vegetable oils were studied. The study was designed as a dose response study with two control diets, one diet based on fish oil (FO) and one diet based on a mixture of linseed and sunflower oil (6:4 by vol.) (MO). As experimental diets three different levels of inclusion of sesamin / episesamin (hereafter named sesamin) to the MO based diet and one diet based on sesame oil and linseed oil (SesO) (1:1 by vol.) were used. The dietary oils were mirrored in the fatty acid profile of the white muscle. Sesamin significantly decreased the levels of 18:3n-3 in the white muscle phospholipid (PL) fraction of all groups fed sesamin, no significant differences were found in the triacylglycerol fraction (TAG). Slightly increased levels of docosahexaenoic acid (22:6n-3, DHA) in PL and TAG were found in some of the sesamin fed groups. Sesamin significantly affected the expression of peroxisome proliferator-activated receptor alpha, scavenger receptor type B and hormone sensitive lipase, in agreement with previous studies on rainbow trout (Oncorhynchus mykiss) and Atlantic salmon (Salmo salar L.) hepatocytes published by our group. No significant effects on toxicological response measured as ethoxyresorufin O-deethylase activity was found. The total cytochrome P450 enzymes were significantly higher in MO 0.29 and SesO group. The amount of alpha- and gamma-tocopherols in liver and the amount of gamma-tocopherol in white muscle were significantly lower in fish fed the FO diet compared to the MO diet, but no difference after inclusion of sesamin was found in this study. Increased inclusion of sesamin increased the levels of sesamin and episesamin in the liver, but did not affect the amounts in white muscle.

Topics: Animals; Cytochrome P-450 CYP1A1; Dioxoles; Fatty Acids; Lignans; Lipid Metabolism; Liver; Salmo salar; Tocopherols

Induction of phase II antioxidant enzymes by activation of Nrf2/ARE (antioxidant response element) signaling has been considered as a promising strategy to combat with oxidative stress-related diseases. In the present study, we tested for potential effects of sesamin, a major lignan contained in sesame seeds, its stereoisomer episesamin, and their metabolites on Nrf2/ARE activation in rat pheochromocytoma PC12 cells. Luciferase reporter assays showed that primary metabolites of sesamin and episesamin, SC-1 and EC-1 were the most potent ARE activators among all tested compounds. SC-1 {(1R,2S,5R,6S)-6-(3,4-dihydroxyphenyl)-2-(3,4-methylenedioxyphenyl)-3,7-dioxabicyclo-[3,3,0]octane} enhanced nuclear translocation of Nrf2 and up-regulated expression of phase II antioxidant enzymes including heme oxygenase-1 (HO-1). Treatment with SC-1 resulted in increased phosphorylation of p38 MAP kinase and transient increase in intracellular ROS levels. N-acetylcysteine (NAC) treatment abolished p38 phosphorylation as well as HO-1 induction caused by SC-1, indicating that ROS are upstream signals of p38 in Nrf2/ARE activation by SC-1. Furthermore, preconditioning with SC-1 attenuated H(2)O(2)-induced cell death in a dose-dependent manner. Finally, treatment with a HO-1 inhibitor, Zn-protoporphyrin (ZnPP), and overexpression of a dominant-negative mutant of Nrf2 diminished SC-1-mediated neuroprotection. Our results demonstrate that SC-1 is capable of protecting against oxidative stress-induced neuronal cell death in part through induction of HO-1 via Nrf2/ARE activation, suggesting its potential to reduce oxidative stress and ameliorate oxidative stress-related neurodegenerative diseases.

Topics: Animals; Apoptosis; Dioxoles; Heme Oxygenase-1; Hydrogen Peroxide; Lignans; NF-E2-Related Factor 2; PC12 Cells; Rats; Seedlings; Sesamum

Sesamin is a major lignan in sesame seed. We confirmed that ingestion of sesamin and α-tocopherol synergistically reduced the concentration of blood cholesterol in rats given a high-cholesterol diet. To elucidate the molecular mechanism behind this effect, we analyzed the gene-expression profiles in rat liver after co-ingestion of sesamin and α-tocopherol. Six-week-old male Sprague-Dawley rats were fed a 1% cholesterol diet (HC) or HC containing 0.2% sesamin, 1% α-tocopherol or sesamin + α-tocopherol for 10 days. Blood samples were collected on days 1, 3, 7, and 10 and livers were excised on day 10. The gene expressions of ATP-binding cassette, sub-family G (WHITE), members 5 (ABCG5) and 8 (ABCG8) were significantly increased, while the gene expression of apolipoprotein (Apo) A4 was significantly decreased. ABCG5 and ABCG8 form a functional heterodimer that acts as a cholesterol efflux transporter, which contributes to the excretion of cholesterol from the liver. ApoA4 controls the secretion of ApoB, which is a component of low-density-lipoprotein cholesterol. These studies indicate that the cholesterol-lowering mechanism underlying the effects of co-ingestion of sesamin and α-tocopherol might be attributable to increased biliary excretion of cholesterol and reduced ApoB secretion into the bloodstream.

Topics: alpha-Tocopherol; Animals; Anticholesteremic Agents; Antioxidants; Apolipoproteins A; ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; Cholesterol; Cholesterol, Dietary; Cholesterol, LDL; Diet, Atherogenic; Dioxoles; Drug Synergism; Gene Expression; Gene Expression Profiling; Lignans; Lipoproteins; Liver; Male; Rats; Rats, Sprague-Dawley

Receptor tyrosine kinase EphB2 and autophagic machinery are known as tumor suppressors; however, the connection remains to be elucidated. Here, we show the link between EphB2 and autophagy. Sesamin, a major lignan in sesame oil, induced autophagy in the human colon cancer cell lines HT29 and LS180, as shown by electron microscopy, as well as Western blotting and immunofluorescence imaging using an anti-LC3 antibody. Receptor tyrosine kinase array analysis revealed that sesamin treatment increased the levels of unphosphorylated -EphA1 and -EphB2 in HT29 cells. Silencing of EphA1 and EphB2 blocked sesamin-induced autophagy as well as sesamin-induced loss of cell viability. These results show that EphA1 and EphB2 play a critical role in this process. The present study reveals a novel function for EphA1 and EphB2 in the induction of autophagy, suggesting a tumor suppressor role for these proteins in colorectal cancer.

Topics: Antineoplastic Agents; Autophagy; Cell Line, Tumor; Cell Survival; Colonic Neoplasms; Dioxoles; Gene Silencing; HT29 Cells; Humans; Lignans; Phosphorylation; Receptor, EphA1; Receptor, EphB2; Tyrosine

Prevention of arterial thrombotic diseases has a high priority in developed countries. An inappropriate diet is known to enhance the risks for acute thrombotic events, and nutritional products experimentally shown to be antithrombotic, might contribute beneficial effects. The present study forms part of a series of investigations into the antithrombotic effect of various foods and vegetables. Roasted and crushed whole grains from six varieties of sesame seeds were added to the diet of mice. Antithrombotic activity was measured in the carotid artery in vivo, using a He-Ne laser-induced thrombosis technique after 12 weeks. Col/Chichibu/Maruteru-2/1995 and T016 varieties showed significant antithrombotic activity, whilst 00037803 was prothrombotic. The acute effects of purified ingredients, sesamin, sesamolin and sesamol, given orally or intra-arterially, were also examined after a single dose. The most effective ingredient was sesamol, followed by sesamolin and sesamin. Daily intake of specific antithrombotic sesame whole grains or purified active ingredients might help to prevent atherothrombotic diseases.

Topics: Administration, Oral; Animals; Benzodioxoles; Diet, High-Fat; Dioxoles; Disease Models, Animal; Edible Grain; Fibrinolytic Agents; Humans; Infusions, Intra-Arterial; Lasers; Lignans; Male; Mice; Mice, Inbred C57BL; Phenols; Plant Extracts; Sesamum; Thrombosis

Kainic acid (KA)-induced status epilepticus (SE) was involved with release of free radicals. Sesamin is a well-known antioxidant from sesame seeds and it scavenges free radicals in several brain injury models. However the neuroprotective mechanism of sesamin to KA-induced seizure has not been studied.. Rodents (male FVB mice and Sprague-Dawley rats) were fed with sesamin extract (90% of sesamin and 10% sesamolin), 15 mg/kg or 30 mg/kg, for 3 days before KA subcutaneous injection. The effect of sesamin on KA-induced cell injury was also investigated on several cellular pathways including neuronal plasticity (RhoA), neurodegeneration (Caspase-3), and inflammation (COX-2) in PC12 cells and microglial BV-2 cells.. Treatment with sesamin extract (30 mg/kg) significantly increased plasma α-tocopherol level 50% and 55.8% from rats without and with KA treatment, respectively. It also decreased malondialdehyde (MDA) from 145% to 117% (p=0.017) and preserved superoxide dismutase from 55% of the vehicle control mice to 81% of sesamin-treated mice, respectively to the normal levels (p=0.013). The treatment significantly decreased the mortality from 22% to 0% in rats. Sesamin was effective to protect PC12 cells and BV-2 cells from KA-injury in a dose-dependent manner. It decreased the release of Ca2+, reactive oxygen species, and MDA from PC12 cells. Western blot analysis revealed that sesamin significantly reduced ERK1/2, p38 mitogen-activated protein kinases, Caspase-3, and COX-2 expression in both cells and RhoA expression in BV-2 cells. Furthermore, Sesamin was able to reduce PGE2 production from both cells under KA-stimulation.. Taken together, it suggests that sesamin could protect KA-induced brain injury through anti-inflammatory and partially antioxidative mechanisms.

Topics: Animals; Antioxidants; Behavior, Animal; Cell Survival; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Dioxoles; Enzyme Activation; Kainic Acid; Lignans; Lipid Peroxidation; Male; Mice; Mitogen-Activated Protein Kinases; Neuroprotective Agents; Oxidative Stress; PC12 Cells; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; rhoA GTP-Binding Protein; Status Epilepticus

Our previous study revealed that CYP2C9 played a central role in sesamin monocatecholization. In this study, we focused on the metabolism of sesamin monocatechol that was further converted into the dicatechol form by cytochrome P450 (P450) or the glucuronide by UDP-glucuronosyltransferase (UGT). Catecholization of sesamin monocatechol enhances its antioxidant activity, whereas glucuronidation strongly reduces its antioxidant activity. In human liver microsomes, the glucuronidation activity was much higher than the catecholization activity toward sesamin monocatechol. In contrast, in rat liver microsomes, catecholization is predominant over glucuronidation. In addition, rat liver produced two isomers of the glucuronide, whereas human liver produced only one glucuronide. These results suggest a significant species-based difference in the metabolism of sesamin between humans and rats. Kinetic studies using recombinant human UGT isoforms identified UGT2B7 as the most important UGT isoform for glucuronidation of sesamin monocatechol. In addition, a good correlation was observed between the glucuronidation activity and UGT2B7-specific activity in in vitro studies using 10 individual human liver microsomes. These results strongly suggest that UGT2B7 plays an important role in glucuronidation of sesamin monocatechol. Interindividual difference among the 10 human liver microsomes is approximately 2-fold. These results, together with our previous results on the metabolism of sesamin by human P450, suggest a small interindividual difference in sesamin metabolism. We observed the methylation activity toward sesamin monocatechol by catechol O-methyl transferase (COMT) in human liver cytosol. On the basis of these results, we concluded that CYP2C9, UGT2B7, and COMT played essential roles in the metabolism of sesamin in the human liver.

Topics: Animals; Aryl Hydrocarbon Hydroxylases; Catechol O-Methyltransferase; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP2C9; Cytochrome P-450 Enzyme System; Dioxoles; Glucuronides; Glucuronosyltransferase; Humans; Intestine, Small; Isoenzymes; Lignans; Liver; Male; Methylation; Microsomes, Liver; NADP; Rats; Rats, Sprague-Dawley; Recombinant Proteins

In this study, we confirmed that sesamin, an active lignan isolated from sesame seed and oil, is a novel skin-tanning compound. The melanin content and tyrosinase activity were increased by sesamin in a dose-dependent manner in B16 melanoma cells. The mRNA and protein levels of tyrosinase were also enhanced after the treatment with sesamin. Western blot analysis revealed that sesamin induced and sustained up-regulation of microphthalmia-associated transcription factor (MITF). Sesamin could activate cAMP response element (CRE) binding protein (CREB), but it had no effect on the phosphorylation of p38 mitogen-activated protein kinase (MAPK) or Akt. Moreover, sesamin activated protein kinase A (PKA) via a cAMP-dependent pathway. Consistent with these results, sesamin-mediated increase of melanin synthesis was reduced significantly by H-89, a PKA inhibitor, but not by SB203580, a p38 MAPK inhibitor or by LY294002, a phosphatidylinositol-3-kinase (PI3K) inhibitor. Sesamin-mediated phosphorylation of CREB and induction of MITF and tyrosinase expression were also inhibited by H-89. These findings indicated that sesamin could stimulate melanogenesis in B16 cells via the up-regulation of MITF and tyrosinase, which was, in turn, due to the activation of cAMP signaling.

Topics: Animals; Antioxidants; Cyclic AMP; Dioxoles; Lignans; Melanoma; Melanosomes; Mice; Microphthalmia-Associated Transcription Factor; Monophenol Monooxygenase; Signal Transduction; Up-Regulation

Effects of bioactive compounds on expression of genes involved in lipid metabolism and fatty acid composition were investigated in Atlantic salmon (Salmo salar L.) primary hepatocytes.. Five treatments were investigated: I) genistein 0.005 mM, II) genistein 0.025 mM, III) lipoic acid 0.2 mM, IV) sesamin/episesamin 0.05 mM, V) sesamin 0.05 mM and compared to controls. The relative expression of genes involved in lipid homeostasis was analysed after 12h and 48h.. Incubation with lipoic acid, sesamin and episesamin/sesamin for 48h had significant effect on all analysed genes involved in lipid uptake, β-oxidation, elongation and desaturation, some effects were detected on the expression of peroxisome prolifertor-activated receptor (PPARs). Also effects on the fatty acid composition were found.. The strongest effect of bioactive copounds on hepatocyte gene expression was detected after 48 hours.

Topics: Animals; Cell Separation; Cell Survival; Culture Media; Dioxoles; DNA, Complementary; Fatty Acids; Gene Expression; Genistein; Hepatocytes; In Vitro Techniques; Indicators and Reagents; Lignans; Lipid Metabolism; Peroxisome Proliferator-Activated Receptors; Real-Time Polymerase Chain Reaction; Salmo salar; Thioctic Acid

The crude bark extract of Zanthoxylum setulosum from Monteverde, Costa Rica was notably cytotoxic (100% kill at 100 microg/mL) to MCF-7, MDA-MB-231, and MDA-MB-468 cells in vitro. Phytochemical studies of the bark extract revealed the triterpenoid lupeol, the lignan sesamin, the sesquiterpene sesquichamaenol, and the xanthone lichexanthone. This is the first report of the isolation of sesquichamaenol and lichexanthone from the bark extract of Z. setulosum. All structures were determined using NMR spectroscopic techniques (1H NMR and 13 degrees C NMR) and GC-MS and by comparison with literature data. Lupeol proved to be the cytotoxic component of Z. setulosum bark.

Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Costa Rica; Dioxoles; Humans; Lignans; Magnetic Resonance Spectroscopy; Pentacyclic Triterpenes; Plant Bark; Plant Extracts; Zanthoxylum

Restoration of blood flow to an ischemic brain region is associated with generation of reactive oxygen species (ROS) with consequent reperfusion injury. ROS cause lipid peroxidation, protein oxidation, and DNA damage, all of which are deleterious to cells. So diminishing the production of free radicals and scavenging them may be a successful therapeutic strategy for the protection of brain tissue in cerebral stroke. The present study investigated the neuroprotective effect of sesamin (Sn) to reduce brain injury after middle cerebral artery occlusion (MCAO). The middle cerebral artery (MCA) of adult male Wistar rat was occluded for 2h and reperfused for 22h. Sesamin is the most abundant lignan in sesame seed oil is a potent antioxidant. Sesamin (30 mg/kg) was given orally twice, 30 min before the onset of ischemia and 12h after reperfusion. The initial investigations revealed that sesamin reduced the neurological deficits in terms of behavior and reduced the level of thiobarbituric acid reactive species (TBARS), and protein carbonyl (PC) in the different areas of the brain when compared with the MCAO group. A significantly depleted level of glutathione and its dependent enzymes (glutathione peroxidase [GPx] and glutathione reductase [GR]) in MCAO group were protected significantly in MCAO group treated with sesamin. The present study suggests that sesamin may be able to attenuate the ischemic cell death and plays a crucial role as a neuroprotectant in regulating levels of reactive oxygen species in the rat brain. Thus, sesamin may be a potential compound in stroke therapy.

Topics: Animals; Antioxidants; Behavior, Animal; Dioxoles; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Infarction, Middle Cerebral Artery; Lignans; Male; Motor Activity; Neuroprotective Agents; Protein Carbonylation; Rats; Rats, Wistar; Reactive Oxygen Species; Sodium-Potassium-Exchanging ATPase; Thiobarbituric Acid Reactive Substances

The natural product sesamin has been known to act as a potent antioxidant and prevent endothelial dysfunction. We here found that sesamin increased in vitro angiogenic processes, such as endothelial cell proliferation, migration, and tube formation, as well as neovascularization in an animal model. This compound elicited the activation of multiple angiogenic signal modulators, such as ERK, Akt, endothelial nitric oxide synthase (eNOS), NO production, FAK, and p38 MAPK, but not Src. The MEK inhibitor PD98059 and the PI3K inhibitor Wortmannin specifically inhibited sesamin-induced activation of the ERK and Akt/eNOS pathways. These inhibitors reduced angiogenic events, with high specificity for MEK/ERK-dependent cell proliferation and migration and PI3K/Akt-mediated tube formation. Moreover, inhibition of p38 MAPK effectively inhibited sesamin-induced cell migration. The angiogenic activity of sesamin was not associated with VEGF expression. Furthermore, this compound did not induce vascular permeability and upregulated ICAM-1 and VCAM-1 expression, which are hallmarks of vascular inflammation. These results suggest that sesamin stimulates angiogenesis in vitro and in vivo through the activation of MEK/ERK-, PI3K/Akt/eNOS-, p125(FAK)-, and p38 MAPK-dependent pathways, without increasing vascular inflammation, and may be used for treating ischemic diseases and tissue regeneration.

Topics: Androstadienes; Animals; Antioxidants; Cell Adhesion Molecules; Cells, Cultured; Dioxoles; Endothelium, Vascular; Extracellular Signal-Regulated MAP Kinases; Flavonoids; Focal Adhesion Kinase 1; Humans; Lignans; Mice; Mice, Inbred BALB C; Neovascularization, Physiologic; Nitric Oxide Synthase Type III; p38 Mitogen-Activated Protein Kinases; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Signal Transduction; src-Family Kinases; Vascular Endothelial Growth Factor A; Wortmannin

The reaction of human leukocytes to chemoattractants is an important component of the host immune response and also plays a crucial role in the development of inflammation. Sesamin has been shown to inhibit lipid peroxidation and regulate cytokine production. In this study, we examined the effect of sesamin on inflammatory responses elicited by the bacterial chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLF) in vitro and in vivo and explored the mechanisms involved. fMLF is recognized by a human G protein-coupled receptor formyl peptide receptor (FPR) on phagocytic leukocytes. Sesamin at concentrations between 12.5 and 50 micromol/L inhibited fMLF-induced chemotaxis of human monocyte cell line THP-1 differentiated with dibutyryl cyclic AMP (P < 0.01). Similarly, sesamin inhibited FPR-transfected rat basophilic leukemia cell [epitope-tagged human FPR (ETFR) cell] migration toward fMLF (P < 0.01). In fMLF-induced inflammation in a murine air-pouch model, intraperitoneal administration of sesamin (12 mgkg(-1)d(-1) for 2 d) suppressed leukocyte infiltration into the air pouch induced by fMLF [(62.89 +/- 7.93) x 10(4) vs. (19.67 +/- 4.43) x 10(4) cells/air pouch; n = 9; P < 0.001]. Ca(2+) mobilization and mitogen-activated protein kinase extracellular signal-regulated kinase (ERK1/2) activation are involved in fMLF-induced leukocyte migration. Pretreatment of ETFR cells with sesamin inhibited fMLF-induced ERK1/2 phosphorylation in a dose-dependent manner but did not affect fMLF-induced Ca(2+) flux. Electrophoretic mobility shift assay showed that pretreatment of THP-1 cells with sesamin dose dependently inhibited fMLF-induced nuclear factor-kappaB (NF-kappaB) activation. These results suggest that sesamin inhibits leukocyte activation by fMLF through ERK1/2- and NF-kappaB-related signaling pathways and thus is a potential compound for the management of inflammatory diseases.

Topics: Animals; Anti-Inflammatory Agents; Bacteria; Basophils; Bucladesine; Calcium; Cell Line; Cell Line, Tumor; Chemotaxis, Leukocyte; Dioxoles; Dose-Response Relationship, Drug; Humans; Inflammation; Leukemia; Leukemic Infiltration; Lignans; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinase 1; Models, Animal; Monocytes; N-Formylmethionine Leucyl-Phenylalanine; NF-kappa B; Phosphorylation; Phytotherapy; Plant Extracts; Rats; Receptors, Formyl Peptide; Sesamum; Signal Transduction

Advances in understanding the neurodegenerative pathologies are creating new opportunities for the development of neuroprotective therapies, such as antioxidant food factors, lifestyle modification and drugs. However, the biomarker by which the effect of the agent on neurodegeneration is determined is limited. We here address hexanoyl dopamine (HED), one of novel dopamine adducts derived from brain polyunsaturated acid, referring to its in vitro formation, potent toxicity to SH-SY5Y cells, and application to assess the neuroprotective effect of antioxidative food factors. Dopamine is a neurotransmitter, and its deficiency is a characterized feature in Parkinson's disease (PD); thus, HED provides a new insight into the understanding of dopamine biology and pathophysiology of PD and a novel biomarker for the assessment of neuroprotective therapies. We have established an analytical system for the detection of HED and its toxicity to the neuroblstoma cell line, SH-SY5Y cells. Here, we discuss the characteristics of the system and its applications to investigate the neuroprotective effect of several antioxidants that originate from food.

Topics: Antioxidants; Cell Line, Tumor; Cell Survival; Chromatography, High Pressure Liquid; Curcumin; Dioxoles; Dopamine; Humans; Lignans; Neuroblastoma; Parkinson Disease; Tandem Mass Spectrometry; Tocopherols; Tocotrienols; Xanthophylls

Animal and clinical studies have suggested that polyphenols in fruits, red wine, and tea may delay the development of atherosclerosis through their antioxidant and anti-inflammatory properties. We investigated whether individual dietary polyphenols representing different polyphenolic classes, namely quercetin (flavonol), (-)-epicatechin (flavan-3-ol), theaflavin (dimeric catechin), sesamin (lignan), or chlorogenic acid (phenolic acid), reduce atherosclerotic lesion formation in the apolipoprotein E (ApoE)(-/-) gene-knockout mouse.. Quercetin and theaflavin (64-mg/kg body mass daily) significantly attenuated atherosclerotic lesion size in the aortic sinus and thoracic aorta (P<0.05 versus ApoE(-/-) control mice). Quercetin significantly reduced aortic F(2)-isoprostane, vascular superoxide, vascular leukotriene B(4), and plasma-sP-selectin concentrations; and augmented vascular endothelial NO synthase activity, heme oxygenase-1 protein, and urinary nitrate excretion (P<0.05 versus control ApoE(-/-) mice). Theaflavin showed similar, although less extensive, significant effects. Although (-)-epicatechin significantly reduced F(2)-isoprostane, superoxide, and endothelin-1 production (P<0.05 versus control ApoE(-/-) mice), it had no significant effect on lesion size. Sesamin and chlorogenic acid treatments exerted no significant effects. Quercetin, but not (-)-epicatechin, significantly increased the expression of heme oxygenase-1 protein in lesions versus ApoE(-/-) controls.. Specific dietary polyphenols, in particular quercetin and theaflavin, may attenuate atherosclerosis in ApoE(-/-) gene-knockout mice by alleviating inflammation, improving NO bioavailability, and inducing heme oxygenase-1. These data suggest that the cardiovascular protection associated with diets rich in fruits, vegetables, and some beverages may in part be the result of flavonoids, such as quercetin.

Topics: Animals; Anti-Inflammatory Agents; Aorta; Aortic Diseases; Apolipoproteins E; Atherosclerosis; Biflavonoids; Biomarkers; Catechin; Chlorogenic Acid; Cholesterol; Diet; Dioxoles; Disease Models, Animal; Endothelin-1; Endothelium, Vascular; F2-Isoprostanes; Fatty Acids; Flavonoids; Heme Oxygenase-1; Inflammation; Leukotriene B4; Lignans; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Nitrates; Nitric Oxide; Nitric Oxide Synthase Type III; Nitrites; Oxidative Stress; P-Selectin; Phenols; Polyphenols; Quercetin; Superoxides

The present study was conducted to investigate the functional and transcriptional modulation of P-glycoprotein (MDR-1) by several dietary ingredients (piperine, capsaicin, daidzein, genistein, sesamin, curcumin, taurine) in vinblastine-resistant colon carcinoma LS-180 cells (LS-180V cells). The amount of rhodamine 123 accumulated in LS-180V cells was significantly increased by capsaicin, piperine and sesamin, whereas it was significantly reduced by daidzein and genistein which stimulated the efflux of rhodamine 123. These results suggest that the P-glycoprotein-mediated efflux is inhibited by piperine, capsaicin and sesamin and stimulated by daidzein and genistein. The concurrent addition of piperine and capsaicin seemed to inhibit synergistically the P-glycoprotein-mediated efflux. Pretreatment with sesamin for 48 h caused a significant increase in MDR1 mRNA expression without a significant effect on the expression of P-glycoprotein or accumulation of rhodamine 123. Similar pretreatment with other ingredients had little effect on the expression of MDR1 mRNA or P-glycoprotein, suggesting that they do not cause transcriptional modulation of P-glycoprotein. Piperine, genistein and curcumin have been suggested to stimulate P-glycoprotein-mediated efflux without increasing P-glycoprotein expression. In LS-180V cells, significant increases in mRNA levels of multi-drug resistance associated protein 1 (MRP1) or MRP3 were observed on pretreatment with capsaicin, daidzein, piperine and sesamin. In conclusion, our results suggest that P-glycoprotein-mediated efflux is significantly affected by dietary ingredients. Also, capsaicin, daidzein, piperine and sesamin increased significantly the mRNA expression of MRP1 or MRP3. Thus, the present study provides further evidence that repeated exposure to dietary ingredients can cause drug-food interactions by affecting the function and mRNA expression of intestinal transporters such as P-glycoprotein.

Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Capsaicin; Cell Line, Tumor; Curcumin; Diet; Dioxoles; Gene Expression Regulation, Neoplastic; Genistein; Humans; Intestinal Mucosa; Isoflavones; Lignans

Sesame lignans have antioxidative and anti-inflammatory properties. We focused on the effects of the lignans sesamin and sesamol on the expression of endothelial-leukocyte adhesion molecules in tumor necrosis factor-alpha (TNF-alpha)-treated human aortic endothelial cells (HAECs). When HAECs were pretreated with sesamin (10 or 100 microM), the TNF-alpha-induced expression of intercellular cell adhesion molecule-1 (ICAM-1) was significantly reduced (35 or 70% decrease, respectively) by Western blotting. Sesamol was less effective at inhibiting ICAM-1 expression (30% decrease at 100 microM). Sesamin and sesamol reduced the marked TNF-alpha-induced increase in human antigen R (HuR) translocation and the interaction between HuR and the 3'UTR of ICAM-1 mRNA. Both significantly reduced the binding of monocytes to TNF-alpha-stimulated HAECs. Sesamin significantly attenuated TNF-alpha-induced ICAM-1 expression and cell adhesion by downregulation of extracellular signal-regulated kinase 1/2 and p38. Furthermore, in vivo, sesamin attenuated intimal thickening and ICAM-1 expression seen in aortas of apolipoprotein-E-deficient mice. Taken together, these data suggest that sesamin inhibits TNF-alpha-induced extracellular signal-regulated kinase/p38 phosphorylation, nuclear translocation of NF-kappaB p65, cytoplasmic translocalization of HuR and thereby suppresses ICAM-1 expression, resulting in reduced adhesion of leukocytes. These results also suggest that sesamin may prevent the development of atherosclerosis and inflammatory responses.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antigens, Surface; Antioxidants; Aorta; Apolipoproteins E; Atherosclerosis; Benzodioxoles; Cell Line; Cells, Cultured; Dioxoles; ELAV Proteins; ELAV-Like Protein 1; Endothelium, Vascular; Gene Expression Regulation; Humans; Intercellular Adhesion Molecule-1; Lignans; Mice; Mice, Knockout; Monocytes; Phenols; Random Allocation; RNA-Binding Proteins; RNA, Messenger; RNA, Small Interfering; Signal Transduction; Tumor Necrosis Factor-alpha

Agents that are safe, affordable, and efficacious are urgently needed for the prevention of chronic diseases such as cancer. Sesamin, a lipid-soluble lignan, is one such agent that belongs to a class of phytoestrogens, isolated from sesame (Sesamum indicum), and has been linked with prevention of hyperlipidemia, hypertension, and carcinogenesis through an unknown mechanism. Because the transcription factor NF-kappaB has been associated with inflammation, carcinogenesis, tumor cell survival, proliferation, invasion, and angiogenesis of cancer, we postulated that sesamin might mediate its effect through the modulation of the NF-kappaB pathway. We found that sesamin inhibited the proliferation of a wide variety of tumor cells including leukemia, multiple myeloma, and cancers of the colon, prostate, breast, pancreas, and lung. Sesamin also potentiated tumor necrosis factor-alpha-induced apoptosis and this correlated with the suppression of gene products linked to cell survival (e.g., Bcl-2 and survivin), proliferation (e.g., cyclin D1), inflammation (e.g., cyclooxygenase-2), invasion (e.g., matrix metalloproteinase-9, intercellular adhesion molecule 1), and angiogenesis (e.g., vascular endothelial growth factor). Sesamin downregulated constitutive and inducible NF-kappaB activation induced by various inflammatory stimuli and carcinogens, and inhibited the degradation of IkappaBalpha, the inhibitor of NF-kappaB, through the suppression of phosphorylation of IkappaBalpha and inhibition of activation of IkappaBalpha protein kinase, thus resulting in the suppression of p65 phosphorylation and nuclear translocation, and NF-kappaB-mediated reporter gene transcription. The inhibition of IkappaBalpha protein kinase activation was found to be mediated through the inhibition of TAK1 kinase. Overall, our results showed that sesamin may have potential against cancer and other chronic diseases through the suppression of a pathway linked to the NF-kappaB signaling.

Topics: Angiogenic Proteins; Antineoplastic Agents; Antioxidants; Cell Line, Tumor; Cell Proliferation; Cell Survival; Dioxoles; Growth Inhibitors; Humans; Lignans; Neoplasm Invasiveness; Neoplasms; Neovascularization, Pathologic; NF-kappa B; Sesame Oil; Signal Transduction

Two novel antioxidants, obtusilactone A (1) and (-)-sesamin (2) have been identified in Cinnamomum kotoense Kanehira. Both showed effective 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity compared with vitamin C, and reducing power compared with BHA. These results suggest that these constituents of C. kotoense act as natural antioxidants and play a potential role in cancer prevention.

Topics: Antioxidants; Biphenyl Compounds; Cinnamomum; Dioxoles; Lignans; Molecular Structure; Oxidation-Reduction; Picrates; Plant Leaves

A new triterpenoid, 3,4-seco-lupane-20(29)-ene-3,28-dioic acid, together with three known lignans, (-)-schisandrin B, (-)-sesamin and (-)-syringaresinol, was isolated from the pulp of Acanthopanax senticosus (Rupr. et Maxim) Harms. Their structures were elucidated by means of physicochemical properties and spectroscopic methods (1D, 2D-NMR and MS).

Topics: Cyclooctanes; Dioxoles; Eleutherococcus; Furans; Lignans; Molecular Structure; Plants, Medicinal; Polycyclic Compounds; Triterpenes

Metabolism of sesamin by cytochrome P450 (P450) was examined using yeast expression system and human liver microsomes. Saccharomyces cerevisiae cells expressing each of human P450 isoforms (CYP1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, and 3A4) were cultivated with sesamin, and monocatechol metabolite was observed in most of P450s. Kinetic analysis using the microsomal fractions of the recombinant S. cerevisiae cells revealed that CYP2C19 had the largest k(cat)/K(m) value. Based on the kinetic data and average contents of the P450 isoforms in the human liver, the putative contribution of P450s for sesamin metabolism was large in the order of CYP2C9, 1A2, 2C19, and 2D6. A good correlation was observed between sesamin catecholization activity and CYP2C9-specific activity in in vitro studies using 10 individual human liver microsomes, strongly suggesting that CYP2C9 is the most important P450 isoform for sesamin catecholization in human liver. Inhibition studies using each anti-P450 isoform-specific antibody confirmed that CYP2C9 was the most important, and the secondary most important P450 was CYP1A2. We also examined the inhibitory effect of sesamin for P450 isoform-specific activities and found a mechanism-based inhibition of CYP2C9 by sesamin. In contrast, no mechanism-based inhibition by sesamin was observed in CYP1A2-specific activity. Our findings strongly suggest that further studies are needed to reveal the interaction between sesamin and therapeutic drugs mainly metabolized by CYP2C9.

Topics: Aryl Hydrocarbon Hydroxylases; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C9; Cytochrome P-450 CYP2D6; Cytochrome P-450 Enzyme System; Dioxoles; Humans; Isoenzymes; Lignans; Microsomes, Liver

Several compounds from Cinnamomum kotoense show anticancer activities. However, the detailed mechanisms of most compounds from C. kotoense remain unknown. In this study, we investigated the anticancer activity of obtusilactone A (OA) and (-)-sesamin in lung cancer. Our results show that human Lon is upregulated in non-small-cell lung cancer (NSCLC) cell lines, and downregulation of Lon triggers caspase-3 mediated apoptosis. Through enzyme-based screening, we identified two small-molecule compounds, obtusilactone A (OA) and (-)-sesamin from C. kotoense, as potent Lon protease inhibitors. Obtusilactone A and (-)-sesamin interact with Ser855 and Lys898 residues in the active site of the Lon protease according to molecular docking analysis. Thus, we suggest that cancer cytotoxicity of the compounds is partly due to the inhibitory effects on Lon protease. In addition, the compounds are able to cause DNA double-strand breaks and activate checkpoints. Treatment with OA and (-)-sesamin induced p53-independent DNA damage responses in NSCLC cells, including G(1) /S checkpoint activation and apoptosis, as evidenced by phosphorylation of checkpoint proteins (H2AX, Nbs1, and Chk2), caspase-3 cleavage, and sub-G(1) accumulation. In conclusion, OA and (-)-sesamin act as both inhibitors of human mitochondrial Lon protease and DNA damage agents to activate the DNA damage checkpoints as well induce apoptosis in NSCLC cells. These dual functions open a bright avenue to develop more selective chemotherapy agents to overcome chemoresistance and sensitize cancer cells to other chemotherapeutics.

Topics: Amino Acid Sequence; Antineoplastic Agents; Apoptosis; Blotting, Western; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Separation; Comet Assay; Dioxoles; DNA Damage; Flow Cytometry; Humans; Lignans; Lung Neoplasms; Mitochondria; Molecular Sequence Data; Protease La; Protein Structure, Quaternary; Signal Transduction

To study the effects of schisandrin B and sesamin mixture on carbon tetrachloride (CCl(4))-induced hepatic oxidative stress in male Sprague-Dawley rats. The rats were randomly assigned to five groups: control group (olive oil injection), CCl(4) group (CCl(4) injection), silymarin group (CCl(4) injection combined with supplementation of silymarin, 7.5 mg/kg/day), low dose group (CCl(4) injection combined with supplementation of schisandrin B and sesamin mixture at a low dose, 43 mg/kg/day) and high dose group (CCl(4) injection combined with the supplementation of schisandrin B and sesamin mixture at a high dose, 215 mg/kg/day). The hepatic superoxide dismutase and glutathione peroxidase activities of rats in the low dose and high dose groups were increased significantly compared with those in the CCl(4) group. The hepatic reduced glutathione concentration in the silymarin, low dose and high dose groups were increased significantly (48%, 45% and 53%, respectively) when compared with those of the CCl(4) group. In addition, the concentration of glutathione in the erythrocytes of the low dose group was significantly higher than the CCl(4) group by 25%. These results suggest that the schisandrin B-sesamin mixture exerted a hepatoprotective effect by improving the antioxidative capacity in rats under CCl(4)-induced hepatic oxidative stress.

Topics: Animals; Antioxidants; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Cyclooctanes; Dioxoles; Drug Combinations; Drugs, Chinese Herbal; Glutathione; Glutathione Peroxidase; Lignans; Liver; Liver Diseases; Male; Oxidative Stress; Polycyclic Compounds; Rats; Rats, Sprague-Dawley; Silymarin; Superoxide Dismutase

Five new compounds, ailanthamide (1), N-(4-methoxyphenethyl)-N-methylbenzamide (2), (2E,4E)-N-isobutyl-6-oxohepta-2,4-dienamide (3), 4-(4'-hydroxy-3'-methylbutoxy)benzaldehyde (4), and (E)-methyl 4-[4-(3-hydroxypropyl)phenoxy]-2-methylbut-2-enoate (5), and 17 known compounds have been isolated from the stem bark of Zanthoxylum ailanthoides. The structures were determined through spectroscopic and MS analyses. Compounds 1, 3, xanthyletin, decarine, (+)-episesamin, (-)-hinokinin, and evofolin-B exhibited inhibition (IC(50) < or = 5.34 microg/mL) of superoxide anion generation by human neutrophils in response to formyl-l-methionyl-l-leucyl-l-phenylalanine/cytochalasin B (fMLP/CB). Compounds 1, xanthyletin, decarine, and (+)-episesamin also inhibited fMLP/CB-induced elastase release with IC(50) values < or = 5.53 microg/mL.

Topics: 4-Butyrolactone; Amides; Benzamides; Benzene Derivatives; Benzodioxoles; Coumarins; Dioxoles; Humans; Inhibitory Concentration 50; Lignans; Molecular Structure; Neutrophils; Pancreatic Elastase; Plant Bark; Plants, Medicinal; Superoxides; Taiwan; Zanthoxylum

The expression of oestrogen receptors (ERalpha and ERbeta) in the prostate and uterus tissues of Wistar rats supplied for 8 weeks with a diet rich in sesame (Sesamum indicum) pericarp (30 %) was monitored. Eight male rats, aged 6 weeks, were divided into a control group fed on a normal diet, and an experimental one, provided with the normal diet enriched with 30 % sesame pericarp. A similar experiment was performed with female rats. At the end of the experiment, the prostate and uterus tissues were surgically removed and kept at - 80 degrees C for up to 2 months. Western blotting and quantitative real-time PCR (qRT-PCR) methods were used in order to investigate the levels of receptor proteins and mRNA. Significant increase in the expression of ERbeta in prostate and uterus was evident in both methods, while the magnitude of the observed alteration depended on the applied method. No statistically significant change was observed in the expression of ERalpha in uterus. In prostate, although the increase was more evident when investigated by means of qRT-PCR, the difference in expression of ERalpha was not statistically significant. In both tissues, a shift of the ratio of ERalpha:ERbeta in favour of ERbeta was evident, indicating, according to existing literature, a beneficial effect of the diet provided upon the health status of the organisms. It is suggested that this effect is attributed to the lignans present in the pericarp which exert phyto-oestrogenic activity.

Topics: Animals; Benzodioxoles; Diet; Dioxoles; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Lignans; Male; Phenols; Phytoestrogens; Prostate; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sesamum; Uterus

A natural component, sesamin (SA), was used to replace conventional amine as co-initiator for dental composite. A combination of camphorquinone (CQ) and SA was employed to initiate the photopolymerization of 2-2-bis[4-(2-hydroxy-3-methacryloxyprop-1-oxy)phenyl] propane/triethylene glycol dimethacrylate (70/30wt.%). The kinetics was recorded by real-time Fourier transform infrared spectroscopy. The mechanical properties were measured by dynamic mechanical analysis, the cell toxicity was investigated by MTT assay and a mixture of CQ and ethyl 4-N,N-dimethylaminobenzoate (EDMAB) was used as control in the same photocuring condition. The results indicated that the addition of SA as co-initiator greatly improved the rate of polymerization and final double-bond conversion (DC) when compared with the system initiated by CQ alone. Compared with EDMAB, the final DC of the CQ/SA system (71%) was slightly lower than that of CQ/EDMAB (76%); SA resulted in approximately the same storage modulus at around 37 degrees C, but a slightly higher glass transition temperature. SA produced lower yellowing effect and good in vitro biocompatibility. The water sorption and solubility for two mixtures were very close and within the range of the ISO 4049 specification. These results suggest that SA is an effective alternative co-initiator to conventional amine. The natural compound characteristics of SA make it more promising than amine in dental resin formulations.

Topics: Animals; Cell Line; Cell Survival; Dental Implants; Dioxoles; Fibroblasts; Light-Curing of Dental Adhesives; Lignans; Materials Testing; Mice; Resins, Synthetic

Sesamin, a major lignan in sesame seeds, exhibits various health benefits. Here, we investigated effects of sesamin, its stereoisomer episesamin, and their metabolites on neuronal differentiation in rat pheochromocytoma PC12 cells. Among all compounds tested, primary metabolites of sesamin and episesamin, SC-1 and EC-1 {S- and R-epimer of 2-(3,4-methylenedioxyphenyl)-6-(3,4-dihydroxyphenyl)-3,7-dioxabicyclo [3.3.0]octane}, were the most potent to induce neuronal differentiation. SC-1 alone induced neuronal differentiation through extracellular signal-regulated kinase (ERK) 1/2 activation that is essential for nerve growth factor (NGF)-induced neuronal differentiation, as shown by the suppression with MEK1/2 inhibitors, PD98059 and U0126. However, SC-1 did not increase phosphorylation of TrkA, a high-affinity NGF receptor, and a TrkA inhibitor, K252a, did not affect SC-1-induced neuronal differentiation. Furthermore, SC-1 potentiated neuronal differentiation in cells co-treated with NGF, which was associated with enhanced ERK1/2 activation and increased expression of neuronal differentiation markers. Interestingly, when treated with SC-1 and a high dose of NGF, formation of synaptic connections and synaptophysin accumulation at the neurite terminals were markedly enhanced. These results indicate that (1) SC-1 alone induces neuronal differentiation, (2) SC-1 potentiates neuronal differentiation in NGF-treated cells, (3) SC-1 enhances formation of synaptic connections in cells treated with a high dose of NGF, all of which are associated with ERK1/2 activation. It is therefore concluded that SC-1 may promote neuronal differentiation by tapping into the ERK1/2-MAPK (mitogen-activated protein kinase) signaling pathway downstream from the TrkA receptor in PC12 cells.

Topics: Animals; Antioxidants; Cell Differentiation; Dioxoles; Dose-Response Relationship, Drug; Drug Synergism; Lignans; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase 3; Nerve Growth Factor; Neural Pathways; Neurogenesis; Neurons; PC12 Cells; Phosphorylation; Rats; Receptor, trkA; Synapses; Synaptophysin

During analysis of certain stability batches of an animal health product, an unknown peak was found at a level above the identification thresholds set by VICH. This unknown species is extremely labile in the gas phase under normal electrospray ionization (ESI) mass spectrometric condition. Multiple ions were detected with no clear indication of which one is the molecular ion. To overcome this challenge, we utilized tandem MS/MS analysis and multiple MS instruments. The slightly different ionization processes between the two different instruments provided strong, complementary evidence leading to the identification of the correct molecular ion. Based on the formula thus determined, the unknown species was found to be related to sesame oil, which is one of the major excipients used in this drug product. The unknown species was eventually identified as asarinin using high resolution LC-MSn in conjunction with mechanism-based stress studies, in which the unknown species was generated based on the degradation chemistry of sesamin as revealed by the LC-MSn analysis. This overall approach in combining LC-MSn analysis along with mechanism-based stress studies can be used as a general strategy for identification of unknown pharmaceutical impurities, especially the degradants related to the active pharmaceutical ingredient (API) and excipients.

Topics: Animals; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Dioxoles; Drug Contamination; Drug Stability; Ions; Lignans; Pharmaceutical Preparations; Sesame Oil; Spectrometry, Mass, Electrospray Ionization; Spectrophotometry, Ultraviolet; Technology, Pharmaceutical; Veterinary Drugs

The present study was designed to evaluate the possible in vivo protective effects of sesamin on hypertension and endothelial function in two-kidney, one-clip renovascular hypertensive rats fed with a high-fat, high-sucrose diet (2K1C rats on HFS diet). Sesamin was orally administered for 8 weeks in 2K1C rats on HFS diet. Then, the serum malondialdehyde level was determined. The protein expression of endothelial nitric oxide synthase (eNOS), nitrotyrosine and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit p47(phox) in aortas was detected by Western blotting. Vasorelaxation response to acetylcholine and nitroprusside, and functional assessment of nitric oxide (NO) bioactivity were also determined in aortic rings. Sesamin treatment reduced systolic blood pressure, improved vasodilatation induced by acetylcholine and enhanced NO bioactivity in the thoracic aortas. These changes were associated with increased eNOS, decreased malondialdehyde content, and reduced nitrotyrosine and p47(phox) protein expression. All these results suggest that chronic treatment with sesamin reduces hypertension and improves endothelial dysfunction through upregulation of eNOS expression and reduction of NO oxidative inactivation in 2K1C rats on HFS diet.

Topics: Animals; Antihypertensive Agents; Aorta; Blood Pressure; Dietary Carbohydrates; Dietary Fats; Dioxoles; Endothelium, Vascular; Gene Expression Regulation; Hypertension, Renovascular; Lignans; Lipids; Male; Malondialdehyde; NADPH Oxidases; Nitric Oxide Synthase Type III; Rats; Rats, Sprague-Dawley; Sucrose; Tyrosine

Advances in understanding the neurodegenerative pathologies are creating new opportunities for the development of neuroprotective therapies, such as antioxidant food factors, lifestyle modification, and drugs. However, the biomarker by which to determine the effect of the agent on neurodegeneration is limited. We here address hexanoyl dopamine (HED), one of novel dopamine adducts derived from brain polyunsaturated acid, referring to its in vitro formation, potent toxicity to SH-SY5Y cells, and application to assess the neuroprotective effect of antioxidative food factors. Dopamine is a neurotransmitter and its deficiency is a characterized feature in Parkinson's disease (PD), thereby HED represents a new addition to understanding of dopamine biology and pathophysiology of PD and a novel biomarker for the assessment of neuroprotective therapies. We have established an analytical system using for the detection of HED and its toxicity to the neuroblstoma cell line, SH-SY5Y cells. Here, we discuss the characteristics of the system and its applications to investigate the neuroprotective effect of several antioxidants that originate from food.

Topics: Antioxidants; Cell Line, Tumor; Cell Survival; Chromatography, High Pressure Liquid; Curcumin; Dioxoles; Dopamine; Food; Humans; Lignans; Neuroprotective Agents; Oxidative Stress; Parkinson Disease; Tandem Mass Spectrometry; Tocopherols; Tocotrienols; Xanthophylls

Lignans are a large class of secondary metabolites in plants, with numerous biological effects in mammals, including antitumor and antioxidant activities. Sesamin, the most abundant furofuran-class lignan in sesame seeds (Sesamum plants), is produced by the cytochrome P450 enzyme CYP81Q1 from the precursor lignan, pinoresinol. In contrast, Forsythia plants produce dibenzylbutyrolactone-class lignans, such as matairesinol, from pinoresinol via the catalysis of pinoresinol/lariciresinol reductase (PLR) and secoisolariciresinol dehydrogenase. Here we present the engineering of lignan biosynthesis in Forsythia cell suspension cultures for the development of an efficient production method of beneficial lignans. A suspension cell culture prepared from leaves of Forsythia koreana produced lignans, mainly pinoresinol and matairesinol glucosides, at levels comparable with that obtained from the leaves. In an attempt to increase the pinoresinol content in Forsythia, we generated a transgenic cell line overexpressing an RNA interference (RNAi) construct of PLR (PLR-RNAi). Down-regulation of PLR expression led to a complete loss of matairesinol and an accumulation of approximately 20-fold pinoresinol in its glucoside form in comparison with the non-transformant. Moreover, the Forsythia transgenic cells co-expressing CYP81Q1 and PLR-RNAi exhibited production of sesamin as well as accumulation of pinoresinol glucoside. These data suggest Forsythia cell suspension to be a promising tool for the engineering of lignan production. To the best of our knowledge, this is the first report on transgenic production of an exogenous lignan in a plant species.

Topics: Cell Culture Techniques; Cells, Cultured; Dioxoles; Forsythia; Furans; Gene Expression Regulation, Plant; Genetic Engineering; Lignans; Molecular Structure; Plant Leaves; Plants, Genetically Modified; RNA Interference; Transformation, Genetic

Sesamin, a lignan from sesame oil, has been shown to have antihypertensive and antioxidative properties. This study examined the effects of sesamin on oxidized low-density lipoprotein (oxLDL)-induced endothelial dysfunction. Oxidative stress was determined by measuring the generation of intracellular reactive oxygen species (ROS) and by measuring the expression levels of superoxide dismutase (SOD) and endothelial nitric oxide synthase (eNOS). To assess the pro-inflammatory effects of oxLDL, ELISA was used to detect IL-8 expression, endothelin-1 (ET-1) secretion, and nuclear factor-kappaB (NF-kappaB) activation. The expression of adhesion molecules (ICAM-1, VCAM-1, and E-selectin) was examined by flow cytometry. In addition, several apoptotic signaling pathways were also investigated. The data showed that sesamin significantly ameliorated oxLDL-induced ROS generation and SOD-1 inactivation. Sesamin also attenuated the oxLDL-induced activation of NF-kappaB, suggesting that the inhibitory effects of sesamin on IL-8 and ET-1 release, adhesion molecule expression, and the adherence of THP-1 cells were at least partially through the blockade of NF-kappaB activation. Furthermore, sesamin attenuated oxLDL-induced apoptotic features, such as intracellular calcium accumulation and the subsequent collapse of mitochondrial membrane potential, release of cytochrome c, and activation of caspase-3. Results from this study may provide insight into possible molecular mechanisms underlying sesamin's beneficial effects against oxLDL-mediated vascular endothelial dysfunction.

Topics: Apoptosis; Cells, Cultured; Dioxoles; E-Selectin; Endothelial Cells; Female; Gene Expression; Humans; Lignans; Lipoproteins, LDL; Oxidative Stress; Pregnancy; Reactive Oxygen Species

We studied the antirejection effect of asarinin, the extract of Herba Asari, in rats that underwent cardiac allograft implantation.. Rats received either olive oil (as a placebo control) or cyclosporine, with various amounts of asarinin or a combination of asarinin and cyclosporine daily through oral administration. 102 recipient SD rats were divided randomly into 7 groups: 1) group A, treated with 8 ml/kg olive oil per day; 2) group B, treated with 2.5 mg/kg cyclosporin A (CsA) each day; 3) group C, treated with 5 mg/kg cyclosporin A (CsA) each day; 4) group D1, treated with 12.5 mg/kg asarinin each day; 5) group D2, treated with 25 mg/kg asarinin each day; 6) group D3, treated with 50 mg/kg asarinin each day; 7) group E, treated with 12.5 mg/kg asarinin and 2.5 mg/kg CsA each day. Allograft survival was observed in each group of rats. On the seventh day posttransplantation; we analyzed weights, pathological lesions, and the levels of interleukin (IL)-2, interferon (IFN)-gamma, IL-4, and IL-10 in peripheral blood.. The survival time of donor hearts in the asarinin groups was significantly prolonged (P < .01) when compared with the control group (7.8 +/- 0.7 days). The weights of rats increased in group C, group D2, group D3, and group E at 7 days after operation. Pathological lesions were significantly less severe. The levels of IL-2 and IFN-gamma decreased remarkably (P < .01), while those of IL-4 and IL-10 were not affected (P > .05) in the asarinin groups (D2 and D3).. Asarinin decreased peripheral blood concentrations of IL-2 and IFN-gamma with prolongation of allograft heart survival.

Topics: Animals; Antioxidants; Cyclosporine; Dioxoles; Drugs, Chinese Herbal; Graft Rejection; Graft Survival; Heart Transplantation; Immunosuppressive Agents; Interferon-gamma; Interleukin-2; Lignans; Models, Molecular; Plant Extracts; Rats; Rats, Sprague-Dawley; Transplantation, Homologous

To study the chemical constituents from the aerial part of Euphorbia chrysocoma.. All compounds were isolated and purified by many methods, including siliga gel and reversed phase RP-18 column chromatographies, preparative thin layer chromatography, Sephadex LH-20, and recrystallization. Their structures were mainly elucidated by ESI-MS and NMR spectra and their physical characters.. Six compounds were isolated from the petroleum ether section from 75% ethanol extraction of the material. Their structures were identified as taraxerol (1), epitaraxerol (2), beta-sistosterol (3), beta-sitostenone (4), jolkinolide E (5), and sesamin (6).. Compounds 1, 2, 4, 5, and 6 are isolated from this plant for the first time.

Topics: Dioxoles; Diterpenes; Euphorbia; Lignans; Molecular Structure; Oleanolic Acid; Plant Components, Aerial; Plants, Medicinal; Sitosterols

The effects of including an equi-mixture of sesamin and episesamin in fish diets based on vegetable oils of different fatty acid composition were examined. Sesamin/episesamin (hereafter named sesamin) was included at 0.58 g/100 g diet. The oil used in the feed was either a mixture of linseed and sunflower oils (6:4, by vol) or 100% linseed oil. Addition of sesamin increased the percentages of docosahexaenoic acid (DHA) in white muscle phospholipid and triacylglycerol fraction by up to 37% but the fatty acids in red muscle and liver were not affected. The expression of the peroxisome proliferator-activated receptor PPARalpha was significantly down regulated in the liver of the fish fed sesamin and mixed oil diet (P < 0.05). Sesamin and episesamin were detected in liver and muscle tissues of the fish that had been fed sesamin. Fish fed sesamin had elevated levels of total cytochrome P450 (CYP) enzymes and EROD activity in the liver, indicating an induction of CYP1A in this tissue. Our conclusion was that supplementation of fish feed with sesamin increased the proportions of DHA in the white muscle.

Topics: alpha-Linolenic Acid; Animal Nutritional Physiological Phenomena; Animals; Antioxidants; Cytochrome P-450 CYP1A1; Dioxoles; Docosahexaenoic Acids; Lignans; Liver; Muscle Fibers, Fast-Twitch; Oncorhynchus mykiss; Plant Oils

In vitro cultivated Atlantic salmon (Salmo salar L.), hepatocytes were incubated without or with a mixture of sesamin and episesamin in order to test for possible effects on lipid metabolism. Sesamin/episesamin exposure (0.05 mM, final concentration) led to increased elongation and desaturation of (14)C 18:3n-3 to docosahexaenoic acid ((14)C 22:6n-3, DHA, P < 0.01) and down regulated gene expression of Delta6 and Delta5 desaturases compared to control treatment. Sesamin/episesamin further increased the hepatocytes capacity for fatty acid beta-oxidation of (14)C 18:3n-3 (P < 0.01) to the (14)C acid soluble products, acetate, malate and oxaloacetate, in agreement with an increased gene expression of carnitine palmitoyltransferase I. Also the gene expression of cluster of differentiation 36 was upregulated and the expression of scavenger receptor type B, peroxisome proliferator-activated receptors alpha and gamma were downregulated. The amount of triacylglycerols secreted by the cells tended to be lower in the sesamin/episesamin incubated hepatocytes than the control cells. This study shows that sesamin has favourable effects on lipid metabolism leading to increased level of DHA, which may be of interest for aquaculture use.

Topics: alpha-Linolenic Acid; Animals; Antioxidants; Dioxoles; Docosahexaenoic Acids; Gene Expression Regulation; Hepatocytes; Lignans; Models, Biological; PPAR alpha; Salmo salar; Stearoyl-CoA Desaturase

The first chemical synthesis of two metabolites ((1R,2S,5R,6S)-6-(3,4-dihydroxyphenyl)-2-(3,4-methylenedioxyphenyl)-3,7-dioxabicyclo[3,3,0]octane (SC-1) and (1R,2S,5R,6S)-2,6-bis(3,4-dihydroxyphenyl)-3,7-dioxabicyclo[3,3,0]octane (SC-2)) of sesamin was achieved by a simple two-step approach from sesamin. The approach consists of acetoxylation of the methylenedioxy moiety(ies) with lead(IV) tetraacetate and acid hydrolysis of the resulting hemiorthoester to SC-1 and SC-2.

Topics: Antioxidants; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Dioxoles; Hydrolysis; Indicators and Reagents; Lignans; Magnetic Resonance Spectroscopy; Organometallic Compounds; Spectrometry, Mass, Electrospray Ionization

1. Dietary sesamin, a sesame lignan, is known to suppress the development of experimental hypertension in rats partly through its inhibitory effect on vascular O(2)(-) production. Therefore, in the present study, we examined whether sesamin feeding had any effect on vascular NADPH oxidase using aortas from deoxycorticosterone acetate (DOCA) salt hypertensive rats. 2. After a 5 week feeding and treatment period, aortic O(2)(-) production and NADPH oxidase activity were measured using the lucigenin assay. Reverse transcription-polymerase chain reaction was performed to analyse aortic expression of NADPH oxidase subunit (p22phox, gp91phox, Nox1 and Nox4) mRNA. 3. Sesamin feeding markedly suppressed DOCA salt-induced hypertension and significantly decreased aortic O(2)(-) production. DOCA salt treatment increased NADPH oxidase activity and elevated aortic mRNA expression of p22phox, gp91phox, Nox1 and Nox4. Sesamin feeding abolished the increase in NADPH oxidase activity and, furthermore, significantly suppressed increases in p22phox, gp91phox and Nox1 mRNA expression. 4. In conclusion, dietary sesamin prevented DOCA salt-induced increases in NADPH oxidase activity and subunit mRNA expression. These effects seem to be involved in the anti-oxidant and antihypertensive effects of sesamin.

Topics: Animals; Aorta; Cyclic N-Oxides; Desoxycorticosterone; Dietary Supplements; Dioxoles; Hypertension; Lignans; Male; NADPH Oxidases; Rats; Rats, Sprague-Dawley; Spin Labels

Bioassay-guided fractionation of the root extract of Asarum sieboldii led to the isolation of the four active compounds (-)-sesamin (1), (2E,4E,8Z,10E)-N-(2-methylpropyl)dodeca-2,4,8,10-tetraenamide (2), kakuol (3), and '3,4,5-trimethoxytoluene' (=1,2,3-trimethoxy-5-methylbenzene; 4), in terms of inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production. Compounds 1-4 showed potent inhibition of NO production, with IC(50) values in the low nanomolar-to-micromolar range. Also isolated were the known compounds methylkakuol (5), '3,5-dimethoxytoluene', safrole, asaricin, methyleugenol, and (-)-asarinin, which were found to be inactive in the above assay. Among the ten known isolates, compounds 1, 2, and 5 were found for the first time in this plant.

Topics: Animals; Aristolochiaceae; Cell Line; Dioxoles; Dose-Response Relationship, Drug; Lignans; Lipopolysaccharides; Mice; Microglia; Molecular Structure; Nitric Oxide; Plant Roots; Polyunsaturated Alkamides; Propiophenones; Stereoisomerism; Structure-Activity Relationship; Toluene

The effect of different forms of sesame-based diets on the concentration of plasma lignans was assayed by estimating the levels of certain lignans (sesame lignans and enterolignans) in the plasma of experimental animals. In a series of experiments, male Wistar rats were fed either a raw sesame-enriched diet or a tahini-enriched diet. The plasma concentration of the lignans (sesame lignans and enterolignans) was determined at various time intervals over a 24 h period after a single administration. Enterodiol and enterolactone concentration in the tahini-treated group was significantly higher than in the raw sesame-treated group. In another series of experiments, male Wistar rats were fed, for 15 d, diets enriched in raw dehulled sesame, sesame perisperm, sesame oil, tahini and a polyphenolic extract derived from the seed perisperm. Enterodiol and enterolactone plasma concentration was high in the case of the sesame perisperm in spite of its low concentration in the assessed sesame lignans. Overall, the levels of the sesame lignans and enterolignans present in plasma seem to be influenced not only by the amount of lignan intake but also by other factors such as the form of the sesame-based diet.

Topics: 4-Butyrolactone; Animal Nutritional Physiological Phenomena; Animals; Diet; Dioxoles; Food Analysis; Lignans; Male; Rats; Rats, Wistar; Seeds; Sesamum

Sesamum (Sesamum indicum) seed and its oil have been in use in Indian traditional medicine, 'Ayurveda' since antiquity. However, there has been no attempt to standardize the polyherbal formulations containing sesamum oil as the main ingredient in terms of its active principle or marker compound. Biologically active lignans in sesamum oil are identified as the marker compound for the oil and its formulations. In this report, a simple, rapid and sensitive HPTLC method is described for the first time to identify and quantify sesamin and sesamolin, the major lignans of the sesamum oil and the method was applied to polyherbal formulations containing the oil for their quantitative estimation. The method was validated in terms of its calibration curve, limits of detection and quantification, precision, accuracy and robustness following standard protocols. The method thus developed was applied to sesamum oil and its commercial herbal formulations to quantify sesamin and sesamolin. The method for fingerprints of the formulations in the form of densitogram following charring of the chromatographic plate was also developed that could be useful for marker-based quality assurance of the polyherbal products containing sesamum oil.

Topics: Biomarkers; Calibration; Chromatography, Thin Layer; Dioxoles; Lignans; Medicine, Ayurvedic; Methanol; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Plant Oils; Reference Standards; Reproducibility of Results; Seeds; Sensitivity and Specificity; Sesame Oil; Sesamum; Solvents; Spectrophotometry, Ultraviolet; Time Factors

We have previously reported that substantial amounts of tocotrienols were present in the skin of animals fed a diet containing a tocopherols and tocotrienols rich fraction (T-mix) extracted from palm oil, and further, that sesame lignans enhanced tocotrienol levels in the skin. The present studies were undertaken to determine whether dietary tocotrienols and those with sesamin could protect the skin from damage induced by UVB irradiation in hairless mice fed four diets: a vitamin E-free diet, a 50 mg/kg alpha-tocopherol diet, a 229 mg/kg T-mix (with 50 mg alpha-tocopherol) diet and a 229 mg/kg T-mix with 2 g/kg sesamin diet. In Experiment 1, mice were fed the diets for 6 wk, and half of the mice were exposed to 180 mJ/cm(2 )of UVB light once daily for 7 d. After the intensity of sunburn was scored, vitamin E and thiobarbituric acid reactive substances (TBARS) concentrations in the skin and liver were determined. In Experiment 2, hairless mice were initiated with a single application of 7, 12-dimethylbenz[a]anthracene (DMBA), then 1 wk later mice were fed the experimental diets and subjected to 180 mJ/cm(2) UVB irradiation twice weekly for 20 wk. Tumor incidences were counted once a week. Tocotrienols were detected in the skin of mice fed T-mix, but their concentrations were significantly lower than for alpha-tocopherol. Sesamin elevated tocotrienol contents in the skin. In spite of the high alpha-tocopherol contents, the effects of alpha-tocopherol on sunburn and incidence of tumor were slight. T-mix fed groups reduced the extent of sunburn and incidence of tumor, and further reduction of sunburn and incidence of tumor were observed in the T-mix with sesamin group. These results suggest that dietary tocotrienols protect the skin more strongly than alpha-tocopherol against damage induced by UVB and sesamin enhances tocotrienol effects.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Antioxidants; Carcinogens; Dioxoles; Drug Synergism; Female; Food, Formulated; Lignans; Liver; Mice; Mice, Hairless; Palm Oil; Papilloma; Plant Oils; Skin; Skin Neoplasms; Sunburn; Thiobarbituric Acid Reactive Substances; Tocotrienols; Ultraviolet Rays; Vitamin E

Effects of sesamin and sesamolin (sesame lignans) on hepatic fatty acid metabolism were compared in rats. Rats were fed either a lignan-free diet, a diet containing 0.6 or 2 g/kg lignan (sesamin or sesamolin), or a diet containing both sesamin (1.4 g/kg) and sesamolin (0.6 g/kg) for 10 d. Sesamin and sesamolin dose-dependently increased the activity and mRNA abundance of various enzymes involved in hepatic fatty acid oxidation. The increase was much greater with sesamolin than with sesamin. These lignans increased parameters of hepatic fatty acid oxidation in an additive manner when added simultaneously to an experimental diet. In contrast, they decreased the activity and mRNA abundance of hepatic lipogenic enzymes despite dose-dependent effects not being necessarily obvious. Sesamin and sesamolin were equally effective in lowering parameters of lipogenesis. Sesamolin accumulated in serum at 33- and 46-fold the level of sesamin at dietary concentrations of 0.6 and 2 g/kg, respectively. The amount of sesamolin accumulated in liver was 10- and 7-fold that of sesamin at the respective dietary levels. Sesamolin rather than sesamin can account for the potent physiological effect of sesame seeds in increasing hepatic fatty acid oxidation observed previously. Differences in bioavailability may contribute to the divergent effects of sesamin and sesamolin on hepatic fatty acid oxidation. Sesamin compared to sesamolin was more effective in reducing serum and liver lipid levels despite sesamolin more strongly increasing hepatic fatty acid oxidation.

Topics: Animals; Base Sequence; Diacylglycerol O-Acyltransferase; Dietary Fats, Unsaturated; Dioxoles; DNA Primers; Dose-Response Relationship, Drug; Fatty Acid Synthases; Fatty Acids; Glycerol-3-Phosphate O-Acyltransferase; Lignans; Lipid Metabolism; Liver; Male; Molecular Sequence Data; Oxidation-Reduction; Rats; Rats, Sprague-Dawley; RNA, Messenger

The synthesis of stereoisomers of acuminatolide is rare and requires complex and time-consuming multistep procedures. Asarinin (1) and sesamin (2), two diasteromeric tetrahydrofurofuran lignans, are efficiently mono-dearylated by methyltrioxorhenium (MTO, I) and hydrogen peroxide (H2O2) or urea hydrogen peroxide adduct (UHP) as primary oxidant to give (-)-(7R,8'R,8R)-acuminatolide (3A) and (+)-(7S,8R,8'R)-acuminatolide (3B), respectively, in high yield and diastereoselectivity (de >98%). The oxidation of 1 was also performed with novel heterogeneous catalysts based on the heterogenation of MTO on poly(4-vinylpyridine) and polystyrene resins. In these latter cases 3A was obtained with a different yield and selectivity depending on the physical-chemical properties of the support. Cytotoxic effects of 3A and 3B in mammalian cell lines in vitro are also reported.

Topics: Animals; Antineoplastic Agents; Dioxoles; Drug Screening Assays, Antitumor; Humans; Lignans; Mice; Molecular Structure; Organometallic Compounds; Oxidation-Reduction; Rhenium; Stereoisomerism; Zanthoxylum

Sesamin, the major sesame oil lignan, is recognized for its health-promoting effects, including the lowering of cholesterol and elevation of gamma-tocopherol in rats and humans. However, little is known about the absorption and metabolism of sesamin in humans. In this study, 6 healthy volunteers took a single dose of sesame oil (508 micromol sesamin) and their urine was collected for four 12-h periods. The urine samples were treated with beta-glucuronidase/sulphatase and extracted with chloroform. The major urinary sesamin metabolite in the chloroform extract was collected using HPLC diode array detector and characterized as (1R,2S,5R,6S)-6-(3,4-dihydroxyphenyl)-2-(3,4-methylenedioxyphenyl)-3,7-dioxabicyclo-[3,3,0]octane using NMR and mass spectroscopy. A quantitative (1)H-NMR technique, based on the methylenedioxyphenyl protons signal (delta 5.91), was used for the quantification of the metabolite in the chloroform extracts of urine. The excretion of the sesamin catechol metabolite ranged from 22.2 to 38.6% (mean +/- SD, 29.3 +/- 5.6) of the ingested dose and happened mainly in the 1st 12 h after ingestion.

Topics: Adult; Catechols; Chromatography, High Pressure Liquid; Dioxoles; Dose-Response Relationship, Drug; Female; Humans; Lignans; Magnetic Resonance Spectroscopy; Male; Mass Spectrometry; Octanes; Pilot Projects; Sesame Oil; Time Factors

The effects of four alkaloids on the biosynthesis of ochratoxin A (OTA), ochratoxin B (OTB) and citrinin were examined on four OTA-producing aspergilli: Aspergillus auricomus, A. sclerotiorum and two isolates of A. alliaceus. Piperine and piperlongumine, natural alkaloids of Piper longum, significantly inhibited OTA production at 0.001% (w/v) for all aspergilli examined. Piperine and piperlongumine affected the polyketide synthesis step of OTA production and inhibited production of citrinin. Curcumin, a constituent of tumeric, completely inhibited mycelial growth of A. alliaceus isolate 791 at 0.1% (w/v) and decreased OTA production by approximately 70% at 0.01% (w/v). Sesamin, a constituent of sesame oil, inhibited OTA and OTB production by 60 and 45%, respectively, at 0.1% (w/v), showing its effect was on chloroperoxidase and polyketide synthase activity. The potential advantage of these natural products to reduce ochratoxin contamination of agricultural commodities is discussed.

Topics: Alkaloids; Antineoplastic Agents, Phytogenic; Antioxidants; Aspergillus; Benzodioxoles; Carcinogens; Citrinin; Culture Media; Curcuma; Curcumin; Dioxolanes; Dioxoles; Food Contamination; Lignans; Mycelium; Mycotoxins; Ochratoxins; Piper; Piperidines; Polyunsaturated Alkamides; Sesame Oil

Sesamin is a major lignan constituent of sesame and possesses multiple functions such as antihypertensive, cholesterol-lowering, lipid-lowering and anticancer activities. Several groups have previously reported that sesamin induces growth inhibition in human cancer cells. However, the nature of this growth inhibitory mechanism remains unknown. The authors here report that sesamin induces growth arrest at the G1 phase in cell cycle progression in the human breast cancer cell line MCF-7. Furthermore, sesamin dephosphorylates tumor-suppressor retinoblastoma protein (RB). It is also shown that inhibition of MCF-7 cell proliferation by sesamin is correlated with down-regulated cyclin D1 protein expression, a proto-oncogene that is overexpressed in many human cancer cells. It was found that sesamin-induced down-regulation of cyclin D1 was inhibited by proteasome inhibitors, suggesting that sesamin suppresses cyclin D1 protein expression by promoting proteasome degradation of cyclin D1 protein. Sesamin down-regulates cyclin D1 protein expression in various kinds of human tumor cells, including lung cancer, transformed renal cells, immortalized keratinocyte, melanoma and osteosarcoma. Furthermore, depletion of cyclin D1 protein using small interfering RNA rendered MCF-7 cells insensitive to the growth inhibitory effects of sesamin, implicating that cyclin D1 is at least partially related to the antiproliferative effects of sesamin. Taken together, these results suggest that the ability of sesamin to down-regulate cyclin D1 protein expression through the activation of proteasome degradation could be one of the mechanisms of the antiproliferative activity of this agent.

Topics: Breast Neoplasms; Cell Line, Transformed; Cell Line, Tumor; Cell Proliferation; Cyclin D; Cyclins; Dioxoles; Down-Regulation; G1 Phase; Growth Inhibitors; Humans; Lignans; Phosphorylation; Protease Inhibitors; Proteasome Endopeptidase Complex; Proteasome Inhibitors; Proto-Oncogene Mas; Retinoblastoma Protein; Sesame Oil

High-resolution electrospray ionization multistage tandem mass spectrometry (MS(1-7)) in positive ion mode was used to determine the accurate masses and the fragmentation pathways of two furofurans, sesamin and gmelinol. The protonated molecules [M+H]+ were absent in the conventional mass spectra of both compounds, but two characteristic ions, [M+H-H(2)O]+ and [M+H-H(2)]+, were always observed. Successive losses of CH(2)O and CO are the common characteristic fragmentations. Based on the exact masses acquired from 21 different tandem mass spectra, two or three fragmentation pathways for each compound are proposed. The consecutive losses of two H(2)O molecules and one H(2) molecule readily take place from the furan rings for both sesamin and gmelinol, resulting in the absence of the protonated molecules in the single-stage experiments. HCHO loss is observed at least three times in the tandem mass spectra, mainly from methylenedioxy groups (OCH(2)O) for sesamin but only from tetrahydrofuran rings for gmelinol. Moreover, CO loss is found at least three times in the tandem mass spectra of both sesamin and gmelinol from the 3,4-methylenedioxyphenyl (ArOCH(2)O) moieties for sesamin and from both the dimethoxyphenyl and the tetrahydrofuran ring moieties for gmelinol. In addition, the disubstituted benzyl cation ArCH(2)+ at m/z 135 for sesamin and at m/z 151 for gmelinol was found in the MS(3) spectra of both sesamin and gmelinol, which is very helpful in the identification of the compositions of 3,4-disubstituted groups on the benzene rings of the furofurans.

Topics: Antihypertensive Agents; Bridged Bicyclo Compounds; Dioxoles; Lignans; Molecular Structure; Reproducibility of Results; Sesame Oil; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry

The oil of tea seed (Camellia oleifera Abel.) is used extensively in China as cooking oil. The objectives of this study were to investigate the antioxidant activity of tea seed oil and its active compounds. Of the five solvent extracts, methanol extract of tea seed oil exhibited the highest yield and the strongest antioxidant activity as determined by DPPH scavenging activity and Trolox equivalent antioxidant capacity (TEAC). Two peaks separated from the methanol extract by HPLC contributed the most significant antioxidant activity. These two peaks were further identified as sesamin and a novel compound: 2,5-bis-benzo[1,3]dioxol-5-yl-tetrahydro-furo [3,4-d][1,3]dioxine (named compound B) by UV absorption and characterized by MS, IR, 1H NMR, and 13C NMR techniques. Sesamin and compound B decreased H2O2-mediated formation of reactive oxygen species in red blood cells (RBCs), inhibited RBCs hemolysis induced by AAPH, and increased the lag time of conjugated dienes formation in human low-density lipoprotein. The results indicate that both compounds isolated from tea seed oil exhibit remarkable antioxidant activity. Apart from the traditional pharmacological effects of Camellia oleifera, the oil of tea seed may also act as a prophylactic agent to prevent free radical related diseases.

Topics: Antioxidants; Camellia; Dioxoles; Hemolysis; Humans; Lignans; Lipid Peroxidation; Lipoproteins, LDL; Magnetic Resonance Spectroscopy; Plant Oils; Reactive Oxygen Species; Seeds

The interaction of sesamin, one of the most abundant lignans in sesame seed, and highly purified docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) in the form of ethyl ester in affecting hepatic fatty acid oxidation was examined in rats. In the first experiment, 3 groups of rats were fed with purified experimental diets free of n-3 fatty acid ethyl ester and containing 0%, 0.2%, and 0.4% sesamin (1:1 mixture of sesamin and episesamin), and 2 groups of animals were fed with a 2% DHA ethyl ester diet containing either 0% or 0.2% sesamin. In the second trial, 4 groups of rats were fed with either a 0% or a 2% EPA ethyl ester diet containing 0% or 0.2% sesamin. After 15 days of feeding, DHA and EPA ethyl esters added to a sesamin-free diet little affected the activity and messenger RNA (mRNA) levels of various enzymes involved in fatty acid oxidation. Sesamin increased the activity levels of various hepatic enzymes involved in fatty acid oxidation irrespective of the presence or absence of n-3 fatty acid ethyl ester in diets. However, the diet containing sesamin and DHA or EPA ethyl ester in combination increased many of these parameters synergistically. In particular, the peroxisomal palmitoyl-coenzyme A oxidation rate and acyl-coenzyme A oxidase activity level were much higher in rats fed with sesamin and DHA or EPA in combination than in animals fed with a diet free of n-3 fatty acid ethyl ester and containing sesamin. Analyses of mRNA levels revealed that a diet simultaneously containing sesamin and n-3 fatty acid ethyl ester increased the gene expression of various enzymes involved in peroxisomal fatty acid oxidation in a synergistic manner. However, the combination of sesamin and n-3 fatty acid ethyl esters was ineffective in causing a synergistic increase in mRNA levels of enzymes of mitochondrial fatty acid oxidation, microsomal cytochrome P-450 IV A1, and cytosolic liver-type fatty acid-binding protein. It was concluded that sesamin and DHA or EPA ethyl ester synergistically increased hepatic fatty acid oxidation primarily through up-regulation of the gene expression of peroxisomal fatty acid oxidation enzymes. The results essentially reproduced those observed in our previous study with a diet containing both fish oil and sesamin despite the fact that DHA and EPA ethyl esters were much less effective than fish oil in increasing hepatic fatty acid oxidation.

Topics: Animals; Dioxoles; Docosahexaenoic Acids; Drug Synergism; Eicosapentaenoic Acid; Enzymes; Fatty Acids; Fatty Acids, Omega-3; Gene Expression Regulation, Enzymologic; Lignans; Lipid Peroxidation; Liver; Male; Oxidation-Reduction; Peroxisomes; Rats; Rats, Sprague-Dawley; RNA, Messenger; Up-Regulation

Plant lignans occur in many foods, with flaxseed presently recognized as the richest source. Some plant lignans can be converted by intestinal microbiota to the mammalian lignans, enterodiol and enterolactone, which may have protective effects against hormone-related diseases such as breast cancer. This study determined whether plant lignans in sesame seed, particularly sesamin, could be metabolized to the mammalian lignans. The total plant lignan concentration in sesame seed (2180 micromol/100 g) was higher than that in flaxseed (820 micromol/100 g). In vitro fermentation with human fecal inoculum showed conversion of sesamin to the mammalian lignans, although at a lower rate (1.1%) compared with that of secoisolariciresinol diglucoside (57.2%). However, when fed to female Sprague-Dawley rats for 10 d, sesamin (15 mg/kg body weight) and a 10% sesame seed diet resulted in greater (P < 0.05) urinary mammalian lignan excretion (3.2 and 11.2 micromol/d, respectively), than the control (< 0.05 micromol/d). We conclude that sesame seed is a rich source of mammalian lignan precursors and sesamin is one of them. From intermediate metabolites of sesamin identified in rat urine by GC-MS, a tentative metabolic pathway of sesamin to mammalian lignans is suggested.

Topics: Animals; Butylene Glycols; Dioxoles; Feces; Female; Fermentation; Flax; Gas Chromatography-Mass Spectrometry; Glucosides; Humans; Lignans; Mass Spectrometry; Rats; Rats, Sprague-Dawley; Seeds; Sesamum

Sesamin, a major lignan in sesame seeds and oil, has been known to lower blood pressure in several types of experimental hypertensive animals. A recent study demonstrated that sesamin metabolites had in vitro radical-scavenging activities. Thus, we determined whether the antioxidative effect of sesamin metabolites modulate the vascular tone and contribute to the in vivo antihypertensive effect of sesamin. We used four demethylated sesamin metabolites: SC-1m (piperitol), SC-1 (demethylpiperitol), SC-2m [(1R,2S,5R,6S)-6-(4-hydroxy-3-methoxyphenyl)-2-(3,4-dihydroxyphenyl)-3,7-dioxabicyclo[3,3,0]octane], and SC-2 [(1R,2S,5R, 6S)-2,6-bis(3,4-dihydroxyphenyl)-3,7-dioxabicyclo-[3,3,0]octane]. SC-1, SC-2m, and SC-2, but not SC-1m, exhibited potent radical-scavenging activities against the xanthine/xanthine oxidase-induced superoxide production. On the other hand, SC-1m, SC-1, and SC-2m produced endothelium-dependent vasorelaxation in phenylephrine-precontracted rat aortic rings, whereas SC-2 had no effect. The SC-1m- and SC-1-induced vasorelaxations were markedly attenuated by pretreatment with a nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine (NOARG), or a soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one. Neither SC-1m nor SC-1 changed the expression level of endothelial NOS protein in aortic tissues. The antihypertensive effects of sesamin feeding were not observed in chronically NOARG-treated rats or in deoxycorticosterone acetate-salt-treated endothelial NOS-deficient mice. These findings suggest that the enhancement of endothelium-dependent vasorelaxation induced by sesamin metabolites is one of the important mechanisms of the in vivo antihypertensive effect of sesamin.

Topics: Animals; Antihypertensive Agents; Antioxidants; Dioxoles; Hypertension; Lignans; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nitric Oxide; Nitric Oxide Synthase Type III; Protein Binding; Rats; Rats, Sprague-Dawley; Vasodilation

The methylenedioxyphenyl moiety in the structure of sesamin and episesamin was changed into the catechol moieties, (1R,2S,5R,6S)-6-(3,4-dihydroxyphenyl)-2-(3,4-methylenedioxyphenyl)-3,7-dioxabicyclo[3,3,0]octane, (1R,2R,5R,6S)-2-(3,4-dihydroxyphenyl)-6-(3,4-methylenedioxyphenyl)-3,7-dioxabicyclo[3,3,0]octane, (1R,2R,5R,6S)-6-(3,4-dihydroxyphenyl)-2-(3,4-methylenedioxyphenyl)-3,7-dioxabicyclo[3,3,0]octane, (1R,2S,5R,6S)-2,6-bis(3,4-dihydroxyphenyl)-3,7-dioxabicyclo[3,3,0]octane, and (1R,2R,5R,6S)-2,6-bis(3,4-dihydroxyphenyl)-3,7-dioxabicyclo[3,3,0]octane, in supercritical water. These products had same structures as the sesamin metabolites which act as antioxidants in the liver. These features suggested the direct preparation of antioxidants from sesamin by a one-step reaction using supercritical water.

Topics: Antioxidants; Chromatography, High Pressure Liquid; Dioxoles; Free Radical Scavengers; Hot Temperature; Lignans; Water

To test the effect of asarinin, the extract of Herba Asari, on the acute heart transplantation rejection and the expression of adhesion molecule.. Asarinin was extracted from herba asari. 64 SD rats undergone heart transplantation were divided into four groups: group A (control group), group B (Cyclosporine A treated), group C (Asarinin treated), and group D (1/2 CsA and 1/2 Asarinin). Some rats were used to examine survival time (n = 8) and the others were used to observe the pathological injury and the expression level of interrellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-I (VCAM-1) by using immunohistochemistry.. Asarinin could prolong the survival time of allografts, which was similar to CsA group (P > 0.05). Asarinin could relieve the damage of cardiomyocytes of the transplanted. Asarinin could also decrease the level of ICAM-1 and VCAM-1 in the allografts.. Asarinin may play important roles in suppressing the immune rejection, prolong the allografts survival time and protect the donor organ, which was similar to CsA. The expression level of ICAM-1 and VCAM-1 is increased in suppressing the course of acute rejection and asarinin can inhibit their expression level. Asarinin can decrease the dosage of CsA.

Topics: Animals; Asarum; Dioxoles; Graft Rejection; Graft Survival; Heart Transplantation; Intercellular Adhesion Molecule-1; Lignans; Male; Myocardium; Plants, Medicinal; Random Allocation; Rats; Rats, Sprague-Dawley; Rats, Wistar; Vascular Cell Adhesion Molecule-1

(+)-Sesamin, a furofuran class lignan, is widespread in vascular plants and represented by Sesamum spp. (+)-Sesamin has been of rapidly growing interest because of its beneficial biological effects in mammals, but its biosynthesis and physiological roles in plants remain to be clarified. It is speculated to be synthesized from (+)-pinoresinol by means of (+)-piperitol by formation of two methylenedioxy bridges mediated by two distinct Sesamum indicum cytochrome P450 (SiP450) proteins. Here, we report an SiP450, CYP81Q1, that alone catalyzes (+)-sesamin biosynthesis from (+)-pinoresinol by means of (+)-piperitol by forming two methylenedioxy bridges. The CYP81Q1 gene expression profile was temporally consistent with the accumulation pattern of (+)-sesamin during seed development. The CYP81Q1-GFP chimera protein was colocalized with an endoplasmic reticulum (ER)-targeting chimera protein, indicating that (+)-sesamin biosynthesis occurs on the ER cytoplasmic surface. Moreover, we isolated two CYP81Q1 homologs from other Sesamum spp. Sesamum radiatum CYP81Q2 showed dual (+)-piperitol/(+)-sesamin synthetic activity. CYP81Q2, as well as CYP81Q1, therefore, corresponds to a (+)-piperitol/(+)-sesamin synthase in lignan biosynthesis. In contrast, Sesamum alatum CYP81Q3 showed no activity, in accord with (+)-sesamin being deficient in S. alatum. Our findings not only provide insight into lignan biosynthesis but also unravel a unique mode of cytochrome P450 action.

Topics: Amino Acid Sequence; Catalysis; Cytochrome P-450 Enzyme System; Dioxoles; Furans; Gene Expression; Gene Expression Profiling; Lignans; Molecular Sequence Data; Plant Proteins; Sesamum

Sesamin, a major lignan from sesame seeds has been associated with cholesterol reduction in previous reports, but recent studies suggested differences in the response to sesamin intake depending on the model studied as well as the nature of the sesamin preparation used.. The effect of pure sesamin epimer on serum lipids was studied in hypercholesterolemic LDL receptor-knockout mice under cholesterol fed condition.. Animals were randomly assigned to 4 groups, fed an atherogenic diet containing stanol ester, sesamin, combination of stanol ester and sesamin or a control diet with no additions.. The control group showed an almost 3-fold increase in serum cholesterol levels due to the atherogenic diet but no effect was seen for triglyceride levels. Stanol ester alone or together with sesamin significantly attenuated the elevation of the cholesterol levels.. Sesamin alone did not affect the elevation of the diet-induced cholesterol level and it did not enhance the effect of stanol ester.

Topics: Animals; Anticholesteremic Agents; Cholesterol; Cholesterol, LDL; Diet, Atherogenic; Dioxoles; Female; Lignans; Mice; Mice, Inbred Strains; Random Allocation; Receptors, LDL; Specific Pathogen-Free Organisms; Triglycerides; Weight Gain

Sesame seed oil increases the survival after cecal ligation and puncture in mice and the increased IL-10 levels with non-lethal lipopolysaccharides (LPS) challenge. We showed that sesamin and sesamolin, major lignans of sesame oil, regulated LPS-induced nitric oxide production in the murine microglia and BV-2 cell line. In this study, we studied the effect of sesamin on cytokine production by LPS stimulation. The result showed that sesamin significantly inhibited LPS-stimulated IL-6 mRNA and protein, and to a lesser degree TNF-alpha, in BV-2 microglia. Sesamin and sesamolin also reduced LPS-activated p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappaB activations. Furthermore, SB203580, a specific inhibitor of p38 MAP kinase, specifically inhibited LPS-induced IL-6 production. These results suggest that sesamin inhibited LPS-induced IL-6 production by suppression of p38 MAPK signal pathway and NF-kappaB activation.

Topics: Animals; Antioxidants; Cytokines; Dioxoles; Interleukin-6; Lignans; Lipopolysaccharides; Mice; NF-kappa B; p38 Mitogen-Activated Protein Kinases; RNA, Messenger

Sesamin and sesaminol triglucoside in sesame seeds are major lignans that display an abundance of biological activities. Although their antioxidative activity in vitro is weak, they have been reported to suppress oxidative stress in vivo. We investigated the production of new antioxidative lignans from sesame lignans by culturing with the genus Aspergillus to enhance the function of food materials. Media containing sesamin or sesaminol triglucoside increased antioxidative activity for DPPH radical scavenging by culturing with Aspergillus usamii mut. shirousamii RIB2503. The antioxidative lignans in sesamin medium were identified as sesamin 2,6-dicatechol and episesamin 2,6-dicatechol. Those in sesaminol triglucoside medium were identified as sesaminol 6-catechol and episesaminol 6-catechol, which are novel antioxidative lignans. It is suggested that they may exhibit higher antioxidative activity than sesamin and sesaminol triglucoside because they have the catechol functional moiety.

Topics: Antioxidants; Aspergillus; Catechols; Dioxoles; Furans; Glucosides; Lignans

The aim of this study was to determine whether sesamin, a component from Acanthopanax senticosus HARMS (ASH) pharmacologically offers protection against Parkinson's disease (PD) and its related depressive behavior in rats administered rotenone. We also examined how sesamin affected the rotenone-induced loss of tyrosine hydroxylase (TH) or glial cell line-derived neurotrophic factor (GDNF)-positive neurons in the midbrain of rats. Rats were orally administered sesamin (3, 30 mg/kg) once a day for 2 weeks before an intraperitoneal injection of rotenone (2.5 mg/kg). The pole test and catalepsy test were used to evaluate the effects of sesamin administration on bradykinesia and depressive behaviors in the PD model of rats given rotenone for 5 weeks. Those effects were compared with the ASH administrated group (250 mg/kg). Treatment with sesamin for seven weeks resulted in prophylactic effects on rotenone-induced parkinsonian bradykinesia and catalepsy, and the effects were equivalent to ASH effects. Immunohistochemistical analysis using TH or GDNF antibody showed that sesamin provided cytoprotective effects against rotenone-induced loss of DA cells. The results suggest that it may be possible to use the ASH and sesamin for the prevention of nigral degenerative disorders, e.g., PD with depression, caused by exposure to pesticide or environmental neurotoxins in general.

Topics: Animals; Depressive Disorder; Dioxoles; Eleutherococcus; Lignans; Male; Parkinsonian Disorders; Plant Bark; Plant Extracts; Rats; Rats, Inbred Lew; Rotenone

Sesamin, a major lignan in sesame seeds, has multiple functions such as cholesterol-lowering and anti-hypertensive activities. To investigate the effect of sesamin on gene expression in the liver, a DNA microarray analysis was carried out. The ingestion of sesamin dissolved in olive oil up-regulated the expression of 38 genes, 16 of which encode proteins possessing a lipid-metabolizing function, and 16 of which encode proteins possessing a xenobiotic/endogenous substance metabolizing function. In particular, sesamin significantly increased the expression of beta-oxidation-associated enzymes in peroxisomes and auxiliary enzymes required for degradation, via the beta-oxidation pathway, of unsaturated fatty acids in mitochondria. The ingestion of sesamin also resulted in an increase in the gene expression of acyl-CoA thioesterase involved in acyl-CoA hydrolase and very-long-chain acyl-CoA thioesterase. Interestingly, it induced the expression of the gene for aldehyde dehydrogenase, an alcohol-metabolizing enzyme. These results suggest that sesamin regulates the metabolism of lipids, xenobiotics, and alcohol at the mRNA level.

Topics: Alcohols; Animals; Dioxoles; Down-Regulation; Gene Expression Regulation, Enzymologic; Lignans; Lipid Metabolism; Liver; Male; Oligonucleotide Array Sequence Analysis; Rats; Rats, Wistar; Seeds; Sesamum; Transcription, Genetic; Up-Regulation

Two natural products, farformolide B and sesamin were isolated from Farfugium japonicum and Cinnamomum kanehirae, respectively. The structures of the two natural products, including their relative stereochemistry, were elucidated using spectroscopic data and theoretical calculations. The molecule 1 (farformolide B) is newly recognized by X-ray crystallography. The two compounds were also investigated by a theoretical analysis using the B3LYP/6-31G* method of the Gaussian 03 package program. The theoretical results were supplemented by experimental data to determine the optimal geometric structures of the two compounds. The calculated molecular mechanics were found to compare well with the experimental data. Several important thermodynamic properties of the two products, including ionization potentials, highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies, energy gaps, heat of formation, atomization energies, and vibration frequencies, were also calculated. The study also provided a good understanding of the stereochemical structure and thermodynamic properties of the two molecules.

Topics: Biological Products; Crystallography, X-Ray; Dioxoles; Lignans; Magnetic Resonance Spectroscopy; Mass Spectrometry; Molecular Conformation; Plants; Sesquiterpenes; Stereoisomerism; Thermodynamics

Sesamin, a major sesame seed lignan, has many biological actions. The specific mechanisms for most of these actions as well as the full metabolic pathway of sesamin in humans are unclear. Two experiments were carried out to determine whether postprandial plasma enterolactone is related to sesamin concentration in sesame seeds and whether enterolactone is the major product of the in vitro fermentation of sesamin. Four subjects (3 women, 1 man) were given a single dose of sesame seeds after they consumed a low-lignan diet for 1 wk. Blood was collected at baseline and at time intervals after intake and plasma was analyzed for plant and mammalian lignan concentrations. Additionally, pure sesamin standard was incubated in vitro with human fecal inoculum to mimic the fermentation process in human gut. We calculated individual pharmacokinetic variables and found high interindividual variation in the plasma plant lignan concentrations. The mammalian lignan appearance rate in plasma shows that sesamin is a major precursor of enterolactone in vivo. In the in vitro experiment, enterolactone was the major metabolite and 3 intermediates were identified, allowing the elucidation of sesamin metabolism in humans. Enterolactone was the major metabolite of sesamin both in vivo and in vitro. The abundance of sesamin in sesame seeds indicates that they are a major food source of enterolactone precursors.

Topics: 4-Butyrolactone; Adult; Biotransformation; Diet; Dioxoles; Female; Humans; Intestinal Absorption; Kinetics; Lignans; Male; Middle Aged

Sesamin (1) and asarinin (2) are two C-7' epimeric lignans. Molecular modeling by semiempirical methods indicated that 1 is more stable than 2 by about 2.5 kcal/mol. However, epimerization under acidic conditions led to a 44.8/55.2 equilibrium ratio of 1 and 2. Single-crystal X-ray diffraction analyses indicated that 1 was monoclinic with a = 10.0435(19) A, b = 6.9151(8) A, c = 11.8460(13) A, and 2 was triclinic with a = 5.595(5) A, b = 9.5910(18) A, c = 15.620(4) A. The unexpected equilibrium ratio of 1 and 2 indicated that structural changes are dependent on the conditions of the extraction processes.

Topics: Crystallography, X-Ray; Dioxoles; Drugs, Chinese Herbal; Lignans; Models, Molecular; Molecular Conformation; Molecular Structure; Plants, Medicinal; Stereoisomerism

Sesamin, a major lignan in sesame seeds, has multiple functions such as stimulation effect of ethanol metabolism in mice and human, and prevention of ethanol-induced fatty liver in rats. However, the mechanism has not been clarified yet.. The changes of gene expression were investigated in rats given 250 mg/kg of sesamin (sesamin rats) or vehicle (control rats) for three days by using a DNA microarray analysis. At 4 hr after the final ingestion, the profiles of gene expression in rat livers were compared.. The analysis showed that 38 transcripts were up-regulated with a significant change of more than two-fold and eight transcripts were down-regulated with a significant change to less than half in the livers of sesamin rats versus control rats. The gene expression levels of the early stage enzymes of beta-oxidation including long-chain acyl-CoA synthetase, very long-chain acyl-CoA synthetase and carnitine palmitoyltransferase were not changed, however, those of the late stage enzymes of beta-oxidation including trifunctional enzyme in mitochondria, and acyl-CoA oxidase, bifunctional enzyme and 3-ketoacyl-CoA thiolase in peroxisomes, were significantly increased by sesamin ingestion. Also, in sesamin rats, the gene expression of aldehyde dehydrogenase was increased about three-fold, whereas alcohol dehydrogenase, liver catalase and CYP2E1 were not changed. Changes in the gene expression of alcohol- and aldehyde-metabolizing enzymes observed in a DNA microarray were also confirmed by a real-time PCR method.. These results suggested that sesamin ingestion regulated the transcription levels of hepatic metabolizing enzymes for alcohol and lipids.

Topics: Aldehyde Dehydrogenase; Animals; Dioxoles; Ethanol; Gene Expression Regulation, Enzymologic; Lignans; Lipid Metabolism; Liver; Male; Oligonucleotide Array Sequence Analysis; Peroxisomes; Rats; Rats, Wistar; Transcription, Genetic

The free radical scavenging capacity (RSC) of antioxidants from sesame cake extract was studied using the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH(*)()) on a kinetic model. Pure lignans and lignan glycosides isolated from methanolic extract by preparative HPLC were used in the study. To understand the kinetic behavior better and to determine the RSC of sesame antioxidants, the second-order rate constant (k(2)) was calculated for the quenching reaction with [DPPH(*)] radical. The k(2) values of the sesame antioxidants were compared with those of butylated hydroxytoluene and alpha-tocopherol. The k(2) values for sesamol, sesamol dimer, sesamin, sesamolin, sesaminol triglucoside, and sesaminol diglucoside were 4.00 x 10(-)(5), 0.50 x 10(-)(5), 0.36 x 10(-)(5), 0.13 x 10(-)(5), 0.33 x 10(-)(5), and 0.08 x 10(-)(5) microM(-)(1) s(-)(1), respectively.

Topics: Antioxidants; Benzodioxoles; Biphenyl Compounds; Dioxoles; Free Radical Scavengers; Free Radicals; Furans; Kinetics; Lignans; Phenols; Picrates; Plant Extracts; Sesamum

The effect of sesame (Sesamum orientale) lignan preparation containing equivalent amounts of sesamin and episesamin on hepatic fatty acid metabolism was compared in rats, mice and hamsters. Animals were fed on either a diet free of lignan or a diet containing 2 g lignan/kg for 15 d. The lignan preparation greatly increased hepatic activity and the mRNA levels of enzymes involved in fatty acid oxidation, while it strongly down-regulated those of enzymes involved in lipogenesis in rats. In contrast, lignan did not modify these variables in mice and hamsters. Changes observed, if any, were more attenuated in these mice and hamsters than in rats. Sesamin and episesamin concentrations in serum and liver of animals fed on lignan-containing diets were significantly greater (P<0.05) in rats than in mice and hamsters. Moreover, sesamin:episesamin values in tissues were far from that expected from the value in the lignan preparation given to the animals and were dependent on the animal species. Liver microsomes from each animal species degraded sesamin and episesamin in the presence of NADPH. The combined value of sesamin and episesamin degradation rates was lower in rats than in mice and hamsters. In addition, there was considerable diversity in the specificity of the enzyme reaction toward sesamin and episesamin among animal species. The differences in the amounts of lignan remaining in the tissues may account for the species dependence of the physiological activity of sesame lignan in affecting hepatic fatty acid oxidation and synthesis.

Topics: Animals; Antioxidants; Blotting, Northern; Cricetinae; Dioxoles; Fatty Acids; Insulin; Lignans; Lipids; Liver; Male; Mesocricetus; Mice; Mice, Inbred ICR; Microsomes, Liver; Oxidation-Reduction; Rats; Rats, Sprague-Dawley; RNA, Messenger; Species Specificity

Acetone and ethanol extracts of the tubercula and several compounds isolated from Aristolochia pubescens (Willd) were bioassayed on velvetbean caterpillars, Anticarsia gemmatalis (Hübner), for evaluation of the insecticidal activities. Of the extracts subjected to bioassay, the acetone extract showed the highest activity. (-)-Cubebin did not show activity against soybean caterpillars, whereas aristolochic acid and ent-kaur-15-en-17-ol increased the larval period. These compounds, and (+)-eudesmin and (+)-sesamin, reduced the viability of this period, giving rise to malformed adults. These extracts and compounds are therefore potential botanical insecticide agents for the control of velvetbean caterpillars in soybean crops.

Topics: Animals; Aristolochia; Aristolochic Acids; Biological Assay; Dioxoles; Diterpenes; Furans; Insecticides; Larva; Lepidoptera; Lignans; Plant Extracts

The interaction of sesamin, one of the most abundant lignans in sesame seed, and types of dietary fats affecting hepatic fatty acid oxidation was examined in rats. Rats were fed purified experimental diets supplemented with 0% or 0.2% sesamin (1:1 mixture of sesamin and episesamin), and containing 8% of either palm, safflower or fish oil for 15 days. Among the groups fed sesamin-free diets, the activity of various fatty acid oxidation enzymes was higher in rats fed fish oil than in those fed palm and safflower oils. Dietary sesamin increased enzyme activities in all groups of rats given different fats. The extent of the increase depended on dietary fat type, and a diet containing sesamin and fish oil in combination appeared to increase many of these parameters synergistically. In particular, the peroxisomal palmitoyl-CoA oxidation rate and acyl-CoA oxidase activity levels were much higher in rats fed sesamin and fish oil in combination than in animals fed sesamin and palm or safflower oil in combination. Analyses of mRNA levels revealed that a diet containing sesamin and fish oil increased the gene expression of various peroxisomal fatty acid oxidation enzymes and PEX11alpha, a peroxisomal membrane protein, in a synergistic manner while it increased the gene expression of mitochondrial fatty acid oxidation enzymes and microsomal cytochrome P-450 IV A1 in an additive manner. It was concluded that a diet containing sesamin and fish oil in combination synergistically increased hepatic fatty acid oxidation primarily through up-regulation of the gene expression of peroxisomal fatty acid oxidation enzymes.

Topics: Animals; Dietary Fats, Unsaturated; Dioxoles; Enzymes; Fatty Acids; Fish Oils; Lignans; Liver; Male; Oxidation-Reduction; Palm Oil; Plant Oils; Rats; RNA, Messenger; Safflower Oil

Sesamin and sesamolin were tested for their ability to protect BV-2 microglia from hypoxia-induced cell death. These antioxidants dose-dependently reduced hypoxia-induced lactate dehydrogenase (LDH) release and dichlorofluorescein (DCF)-sensitive reactive oxygen species (ROS) production. Their effects on signaling pathway mitogen-activated protein kinases (MAPKs) and caspase-3 in hypoxia-induced cell death were further examined. Extracellular signal-regulated protein kinases (ERK1/2), c-jun NH(2)-terminal kinase (JNK), and p38 MAPKs were activated during hypoxia. The sesamin or sesamolin reduced caspase-3 and MAPK activation correlated well with diminished LDH release in BV-2 cells under hypoxia. Furthermore, they preserved superoxide dismutase (SOD) and catalase activities in BV-2 cells under hypoxia. Taken together, these results indicate that the mechanism of sesame antioxidants involves inhibition of MAPK pathways and apoptosis through scavenging of ROS in hypoxia-stressed BV-2 cells.

Topics: Animals; Antioxidants; Blotting, Western; Caspase 3; Caspases; Catalase; Cell Hypoxia; Cell Line; Cell Survival; Dioxoles; Dose-Response Relationship, Drug; L-Lactate Dehydrogenase; Lignans; Mice; Microglia; Mitogen-Activated Protein Kinases; Reactive Oxygen Species; Tetrazolium Salts; Thiazoles

The high stability of sesame oil against oxidative deterioration is attributed to lignans in its non-glycerol fraction. The present study evaluates the effects of feeding sesame lignans (sesamin and sesamolin) on Fe2+-induced oxidative stress in rats. Three groups, each of sixteen male weanling WNIN rats, were fed diets containing 200 g casein/kg and l00 g oil/kg (group 1, groundnut oil; group 2, sesame oil; group 3,sesame oil + sesamin (0.4 g/kg). After 45 d of feeding, eight rats from each group were injected with saline (9 g Na Cl/l, controls) intraperitoneally while the remaining eight rats were injected with 30 mg Fe2+/kg body weight as ferrous sulfate in normal saline. The animals were killed after 90 min to evaluate hepatic function and antioxidant status. Compared with those fed groundnut oil (group 1), sesame oil-fed rats(groups 2 and 3) had lower levels of hepatic thiobarbituric acid-reactive substances, serum glutamate:oxaloacetate transaminase activities and serum glutamate pyruvate transaminase activities, indicating protection against Fe-induced oxidative stress. Despite similar tocopherol levels in the three diets, hepatic a-tocopherol levels were higher in rats fed the sesame-oil diets (groups 2 and 3) compared with controls (group 1).However, activities of hepatic antioxidant enzymes (superoxide dismutase and glutathione peroxidase) were significantly (P< 0-05) increased only in rats fed higher levels of lignans (group 3). These observations suggest that sesame lignans may have sparing effects on tocopherols. The increased bioavailability of tocopherols in the presence of dietary lignans might be due to the regeneration of oxidized tocopherols. The synergistic effects of lignans with tocols has nutritional and therapeutic implications.

Topics: Alanine Transaminase; Animals; Antioxidants; Aspartate Aminotransferases; Diet; Dioxoles; Glutathione Peroxidase; Iron; Lignans; Lipid Peroxidation; Liver; Male; Oxidative Stress; Rats; Sesame Oil; Superoxide Dismutase; Tocopherols

Sesamin has been proved to be antihypertensive. Nitric oxide (NO) is the most important vascular relaxing factor that is regulated in endothelium. Endothelin-1 (ET-1) is characterized as a potent vasoconstrictor and is also regulated in endothelium. Alterations in the endothelial production of NO and ET-1 are known to correlate with hypertension. This study investigated the effect of sesamin on NO and ET-1 in the human umbilical vein endothelial cells (HUVECs).. The concentrations of NO and ET-1 in the medium of HUVECs treated by sesamin were measured. The mRNA and protein expressions of nitric oxide synthase (NOS), endothelin converting enzyme-1 (ECE-1), and endothelin-1 (ET-1) were also investigated. Other than the mRNA and protein expression, NOS activity and cyclic GMP (cGMP) were detected.. The NO concentration was detected by colorimetric assay. The cGMP and ET-1 were analyzed by EIA. The eNOS, ECE-1, and ET-1 mRNA expressions were assayed by Northern blot. The eNOS and ECE-1 protein expressions were analyzed by Western blot. The NOS activity was assayed by detecting the level of [H]-1-citrullin transformed from [H]-1-arginine.. Sesamin not only increased the NO concentration in the medium of HUVECs in a dose-dependent manner after 24 h, but also induced eNOS mRNA and protein expressions. NOS activity in the HUVECs was also induced by sesamin. The content of cGMP was induced by sesamin through NO signaling. On the other hand, the ET-1 concentration in the medium of HUVECs treated by sesamin was suppressed in a dose-dependent manner after 24 h. The ECE-1 protein and mRNA expressions were also inhibited by sesamin. However, the mRNA expression of prepro ET-1 was not influenced by sesamin.. From the above results, it is suggested that sesamin may improve hypertension by its ability to induce NO and inhibit ET-1 production from endothelial cells. The increase of NO by sesamin is through the induction of eNOS gene expression. The decrease of ET-1 by sesamin is through the inhibition of ECE gene expression, but is not through the inhibition of prepro ET-1 gene expression.

Topics: Antihypertensive Agents; Aspartic Acid Endopeptidases; Cells, Cultured; Culture Media; Cyclic GMP; Dioxoles; Endothelial Cells; Endothelin-1; Endothelin-Converting Enzymes; Enzyme Induction; Humans; Lignans; Metalloendopeptidases; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Osmolar Concentration; RNA, Messenger; Signal Transduction

Sesamin was orally administered to rats, and blood, bile and urine were collected periodically. Over 40% of the dose of sesamin was detected in bile as glucuronides of 2-(3, 4-methylenedioxyphenyl)-6-(3, 4-dihydroxyphenyl)-cis-dioxabicyclo[3.3.0] octane and 2-(3, 4-dihydroxyphenyl)-6-(3, 4-dihydroxyphenyl)-cis-dioxabicyclo[3.3.0] octane by 24 hr after administration. Antioxidant activities of these metabolites were compared and catechol metabolites showed strong radical scavenging activities against not only superoxide anion radical but also hydroxyl radical. It was suggested that sesamin was absorbed by the route of portal vein and metabolized to mono- or di-catechol metabolite by drug metabolizing enzymes in the liver cells. Both metabolites exhibited antioxidant activity in the liver and were finally conjugated with glucuronic acid and to excrete in bile. Sesamin can be classified as a pro-antioxidant. The profiles of gene expression of the liver in rats given sesamin or vehicle were compared. The gene expression levels of the late stage enzymes of beta-oxidation including trifunctional enzyme, acyl-CoA oxidase, bifunctional enzyme and 3-ketoacyl-CoA thiolase were significantly increased by sesamin. On the other hand, the transcription of the genes encoding the enzymes for fatty acid synthesis was decreased. Moreover, in sesamin rats, the gene expression of aldehyde dehydrogenase was increased about 3-fold, whereas alcohol dehydrogenase, liver catalase and CYP2E1 were not changed. These results suggested that sesamin ingestion regulated the transcription levels of hepatic metabolizing enzymes for lipids and alcohol.

Topics: Administration, Oral; Alcohol Drinking; Animals; Antioxidants; Body Temperature; Dioxoles; Ethanol; Exercise; Glucuronides; Humans; Lignans; Lipid Metabolism; Lipid Peroxidation; Liver; Oligonucleotide Array Sequence Analysis; Phytotherapy; Rats; Seeds; Sesamum; Tissue Distribution

The preventive effects of sesamin, a lignan from sesame oil and vitamin E on hypertension and thrombosis were examined using stroke-prone spontaneously hypertensive rats (SHRSP). Animals at 5 weeks of age were separated into four groups: (i) control group; (ii) vitamin E group, which was given 1000 mg alpha-tocopherol/kg diet; (iii) sesamin group, given 1000 mg sesamin/kg diet; and (iv) vitamin E plus sesamin group, given 1000 mg alpha-tocopherol plus 1000 mg sesamin/kg diet for 5 weeks from 5 to 10 weeks of age. Resting blood pressure was measured by the tail-cuff method once weekly. A closed cranial window was created in the right parietal bone of the rat and platelet-rich thrombi were induced in vivo using a helium-neon laser technique. The number of laser pulses required for formation of an occlusive thrombus was used as an index of thrombotic tendency. In control rats, systolic blood pressure and the amount of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) became significantly elevated with age. However, the elevation in blood pressure and 8-OHdG were significantly suppressed in rats administered vitamin E, sesamin, or vitamin E plus sesamin. At 10 weeks, the number of laser pulses required to induce an occlusive thrombus in arterioles of the control group was significantly lower than in the other groups (P < 0.05). These results indicate that chronic ingestion of vitamin E and sesamin attenuated both elevation in blood pressure, oxidative stress and thrombotic tendency, suggesting that these treatments might be beneficial in the prevention of hypertension and stroke.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antihypertensive Agents; Antioxidants; Blood Pressure; Deoxyguanosine; Dioxoles; Fibrinolytic Agents; Hypertension; Intracranial Thrombosis; Lignans; Rats; Rats, Inbred SHR; Stroke; Vitamin E

Sesame seed and oil consumption previously increased human plasma gamma-tocopherol (gamma-T) concentrations. This was attributed to the sesame lignans sesamin and sesamolin. Here, we studied the inhibition of vitamin E metabolism by a single dose of sesame oil lignans coingested with deuterated alpha- and gamma-tocopherols in human volunteers. The urinary excretion of gamma-T metabolites was significantly lower in sesame oil treated than in control subjects. Concentrations of tocopherols in blood were not affected by the treatment. In conclusion, a single dose of sesame oil, containing 136 mg sesame lignans (sesamin and sesamolin), reduces the urinary excretion of co-administered gamma-T in humans.

Topics: alpha-Tocopherol; Chromans; Deuterium; Diet; Dioxoles; Food; gamma-Tocopherol; Humans; Kinetics; Lignans; Sesame Oil

Sesamin, a major lignan in sesame oil, is known to have many biological activities, especially protective effects against oxidative damage in the liver. As sesamin itself has no antioxidative properties in vitro, to elucidate the mechanism of its antioxidative effects, the reaction products of sesamin in rat liver homogenate were analyzed. The methylenedioxyphenyl moiety in the structure of sesamin was shown to be changed into a dihydrophenyl (catechol) moiety. The enzymatic reaction products in vitro were identified as (1R,2S,5R,6S)-6-(3,4-dihydroxyphenyl)-2-(3,4-methylenedioxyphenyl)-3,7-dioxabicyclo[3,3,0]octane and (1R,2S,5R,6S)-2,6-bis(3,4-dihydroxyphenyl)-3,7-dioxabicyclo[3,3,0]octane, which showed strong radical scavenging activities; the latter was a novel compound. The same metabolites were found as glucuronic acid and/or sulfic acid conjugates in substantial amounts in rat bile after oral administration of sesamin. It is suggested that sesamin is a prodrug and the metabolites containing the catechol moieties in their structures are responsible for the protective effects of sesamin against oxidative damage in the liver.

Topics: Animals; Antioxidants; Bile; Biphenyl Compounds; Chromatography, High Pressure Liquid; Dioxoles; Free Radical Scavengers; Hydroxyl Radical; Lignans; Lipid Peroxidation; Liver; Magnetic Resonance Spectroscopy; Male; Picrates; Rats; Rats, Wistar; Spectrometry, Mass, Electrospray Ionization

To investigate the mechanism of antioxidative effects of sesamin in vivo, 32 male ddY mice were administered with 10 mg/kg or 100 mg/kg of sesamin (S10, S100), 100 mg/kg of vitamin E (VE100) or control sample (C). They were subjected to 30 min of swimming exercise 2 h after the sample administration by using a new forced-swimming apparatus, i. e. an adjustable-current swimming pool. Exercise resulted in a significant increase in plasma lipid peroxides (LPO) in C and VE100 (p < 0.01), but not in S10 and S100. S100 showed significantly higher total glutathione peroxidase activity and glutathione S-transferase activity in liver compared to C (p < 0.05). In conclusion, sesamin may enhance LPO degradation in the liver resulting in the strong protective effects against exercise-induced plasma lipid peroxidation.

Topics: Animals; Antioxidants; Dioxoles; Enzyme Activation; Glutathione Peroxidase; Humans; Lignans; Lipid Peroxidation; Lipid Peroxides; Male; Mice; Physical Conditioning, Animal

Reactive oxygen species (ROS) are important mediators of a variety of pathological processes, including inflammation and ischemic injury. The neuroprotective effects of sesame antioxidants, sesamin and sesamolin, against hypoxia or H2O2-induced cell injury were evaluated by cell viability or lactate dehydrogenase (LDH) activity. Sesamin and sesamolin reduced LDH release of PC12 cells under hypoxia or H2O2-stress in a dose-dependent manner. Dichlorofluorescein (DCF)-sensitive ROS production was induced in PC12 cells by hypoxia or H2O2-stress but was diminished in the presence of sesamin and sesamolin. We evaluated further the role of mitogen-activated protein kinases (MAPKs) and caspase-3 in hypoxia-induced PC12 cell death. Extracellular signal-regulated protein kinase (ERK) 1, c-jun N-terminal kinase (JNK), and p38 MAPKs of signaling pathways were activated during hypoxia. We found that the inhibition of MAPKs and caspase-3 by sesamin and sesamolin correlated well with the reduction in LDH release under hypoxia. Furthermore, the hypoxia-induced apoptotic-like cell death in cultured cortical cells as detected by a fluorescent DNA binding dye was reduced significantly by sesamin and sesamolin. Taken together, these results suggest that the protective effect of sesamin and sesamolin on hypoxic neuronal and PC12 cells might be related to suppression of ROS generation and MAPK activation.

Topics: Animals; Cell Death; Cell Hypoxia; Cells, Cultured; Cytoprotection; Dioxoles; Dose-Response Relationship, Drug; Lignans; Neurons; PC12 Cells; Rats; Rats, Sprague-Dawley

The effects of dietary (+)-catechin (CAT) and BHT on plasma and tissue concentrations of alpha-tocopherol (alpha-T), gamma-tocopherol (gamma-T) and cholesterol (C) were studied in male Sprague-Dawley rats. The rats were fed the compounds during a 4-wk period at concentrations of 2 g/kg in standardized diets, low but adequate in vitamin E, with 2 g/kg cholesterol. The CAT-regimen did not affect weight gain, feed intake or organ weights. BHT did not affect feed intake but lowered the body weight and the amount of liver lipids and increased the weights of livers and lungs relative to the body weight. Rats consuming CAT had 2.5-3.5-fold increased plasma, liver and lung alpha-T concentrations, but C concentrations remained unchanged. BHT-feeding resulted in 2.4- and 1.7-fold elevation in alpha-T but approximately 50% decrease in gamma-T concentrations in blood plasma and liver, respectively. BHT also lowered total C in the liver without affecting the concentration of C in the liver lipids. To investigate whether the alpha-T-sparing action of the studied compounds was due to the inhibition of tocopherol-omega-hydroxylase, HepG2 cells were incubated with CAT or BHT in the presence of delta-tocopherol (delta-T) and the 3'- and 5'-delta-carboxychromanol metabolites in the media were analyzed by GC/MS. Neither CAT nor BHT inhibited tocopherol-omega-hydroxylase activity in hepatocyte cultures; CAT was also inactive in a rat microsomal assay. In conclusion, both dietary CAT and BHT markedly increased alpha-T concentrations in plasma and organs of Sprague-Dawley rats by a mechanism that apparently does not involve inhibition of tocopherol-omega-hydroxylase, a key enzyme in tocopherol catabolism.

Topics: alpha-Tocopherol; Animals; Antioxidants; Body Weight; Butylated Hydroxytoluene; Catechin; Cells, Cultured; Cholesterol; Diet; Dioxoles; Enzyme Inhibitors; gamma-Tocopherol; Hepatocytes; Lignans; Lipids; Liver; Lung; Male; Mixed Function Oxygenases; Organ Size; Rats; Rats, Sprague-Dawley

We have previously reported that dietary sesamin and sesaminol, major lignans of sesame seed, elevate the alpha-tocopherol concentration and decrease the thiobarbituric acid reactive substance (TBARS) concentration in the plasma and liver of rats. In this study, the effects of dietary sesamin and sesaminol on the lipid peroxidation in the plasma and tissues of rats fed docosahexaenoic acid (DHA, 22:6 n-3) were examined. Male Wistar rats (4-wk-old) were divided into the following six experimental groups: control group, fed a basal diet: sesamin group, fed a diet with sesamin (2 g/kg); sesaminol group, fed a diet with sesaminol (2 g/kg); DHA group, fed a diet containing DHA (5 g/kg); DHA + sesamin group, fed a diet containing DHA with sesamin; and DHA + sesaminol group, fed a diet containing DHA with sesaminol. Each diet contained either 0.01 or 0.05 g D-alpha-tocopherol/kg, and the rats were fed the respective experimental diet for 5 wk. The dietary DHA elevated the TBARS concentration and also increased the red blood-cell hemolysis induced by the dialuric acid. The dietary sesamin and sesaminol lowered the TBARS concentrations and decreased the red blood hemolysis. The dietary sesamin and sesaminol elevated the alpha-tocopherol concentrations in the plasma, liver, and brain of the rats fed a diet with or without DHA. These results suggest that dietary sesame lignans decrease lipid peroxidation as a result of elevating the alpha-tocopherol concentration in rats fed DHA.

Topics: alpha-Tocopherol; Animals; Antioxidants; Brain; Dioxoles; Docosahexaenoic Acids; Dose-Response Relationship, Drug; Furans; Hemolysis; Lignans; Lipid Peroxidation; Liver; Male; Random Allocation; Rats; Rats, Wistar; Sesamum; Thiobarbituric Acid Reactive Substances

In the present study, we evaluated the relationship between the antihypertensive effect of sesamin, a lignan from sesame oil, and its antioxidative activity in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. After a 5-week treatment period, systolic blood pressure was significantly elevated in normal diet-fed DOCA-salt animals compared with cases in sham-operated animals. Sesamin feeding, tempol (a superoxide dismutase mimetic) treatment or antihypertensive drugs combination (triple therapy; reserpine, hydralazine, hydrochlorothiazide) significantly suppressed the development of DOCA-salt-induced hypertension. Compared with sham-operated rats, the normal diet-fed DOCA-salt rats revealed marked increases in aortic superoxide (O(2)(-)) production. These increases in O(2)(-) production were significantly suppressed by sesamin feeding or tempol treatment, but not by triple therapy. Acetylcholine (Ach)-induced endothelium-dependent relaxation was markedly decreased in normal diet-fed DOCA-salt rats, compared with cases in sham-operated rats. Sesamin feeding and triple therapy significantly improved the DOCA-salt-induced impairment of endothelium-dependent relaxation. However, tempol treatment had no effect on the impaired vasodilator responses induced by DOCA-salt treatment. In DOCA-salt rats with or without sesamin feeding, systolic blood pressure significantly correlated with both aortic O(2)(-) production and endothelium-dependent vascular relaxation. These findings suggest that sesamin feeding inhibits the enhancement of aortic O(2)(-) production in DOCA-salt hypertensive rats, and this effect may contribute to the antihypertensive effect of sesamin. Sesamin feeding-induced improvement of endothelial dysfunction seems to result from the above antioxidative and antihypertensive effects.

Topics: Acetylcholine; Administration, Oral; Animals; Antihypertensive Agents; Aorta; Blood Pressure; Cyclic N-Oxides; Desoxycorticosterone; Dioxoles; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Drug Therapy, Combination; Endothelium, Vascular; Hypertension; Hypertension, Renovascular; Lignans; Male; Muscle, Smooth, Vascular; Oxidative Stress; Rats; Rats, Sprague-Dawley; Spin Labels; Superoxides; Vasodilation

In this study, we examined the effects of sesamin and vegetable oil on the concentrations of polyunsaturated fatty acid (PUFA) and lipids (triacylglycerol, free cholesterol, and phospholipid), and beta-oxidation enzyme activities in the rat liver. Rats were fed a diet containing 5% (low-fat diet) or 20% (high-fat diet) salad oil (rapeseed oil: soybean oil, 7:3) with or without sesamin (0.5% w/w) for 4 wk. As a result, the concentrations of linoleic acid (LA, n-6), alpha-linolenic acid (ALA, n-3), and total PUFA in the liver increased significantly as the result of the high-fat diet. In the high-fat diet groups, sesamin administration decreased the concentrations of LA, ALA, and total PUFA to almost the same level as the low-fat diet group, while it increased the concentrations of dihomo-gamma-linolenic acid (DGLA, n-6) and arachidonic acid (AA, n-6). The activities of carnitine acyltransferase and acyl-CoA dehydrogenase in liver mitochondria were enhanced by the intake of the high-fat diet, and were further enhanced by the administration of sesamin. Peroxisomal acyl-CoA oxidase activity was also enhanced by sesamin, while it was not affected by the dietary fat level. These results suggest that sesamin suppressed the increase of hepatic PUFA concentration caused by feeding the high-fat diet through enhancing the enzyme activities of fatty acid beta-oxidation and PUFA metabolism from LA and ALA.

Topics: 8,11,14-Eicosatrienoic Acid; Acyl-CoA Dehydrogenase; alpha-Linolenic Acid; Animals; Arachidonic Acid; Carnitine Acyltransferases; Dietary Fats; Dioxoles; Fatty Acids, Monounsaturated; Fatty Acids, Unsaturated; Lignans; Linoleic Acid; Liver; Male; Mitochondria, Liver; Plant Oils; Rapeseed Oil; Rats; Rats, Wistar; Soybean Oil

Sesamin, a lignan in sesame seeds and sesame seed oil, and capsaicin, the pungent principle of hot red pepper, affect lipid metabolism. Sesamin specifically inhibits delta5 desaturase activity in the Mortierella alpina fungus and rat liver microsomes, however, the effects of sesamin and capsaicin on mRNA expressions of delta6 and delta5 desaturases are not still clear. In this study, we investigated the effects of sesamin and capsaicin on the desaturation indexes of delta6 [(gamma-linolenic acid+dihomo-gamma-linolenic acid)/linolenic acid, (GLA+DGLA)/LA] and delta5 (arachidonic acid/DGLA, AA/DGLA) and mRNA expressions of delta6 and delta5 desaturases in rat primary cultured hepatocytes. To measure the mRNA expressions of delta6 and delta5 desaturase, hepatocytes were cultured in the presence of sesamin or capsaicin for 24 h. To investigate the delta6 or delta5 desaturation index, hepatocytes were cultured in the presence of LA or DGLA, respectively, with sesamin or capsaicin for 24 h. The fatty acid composition of the cells was measured by GLC. The mRNA expressions of delta6 and delta5 desaturases were detected by real time quantitative RT-PCR. Sesamin and capsaicin had no effect on the mRNA expressions of delta6 and delta5 desaturases in rat hepatocytes. Capsaicin had no effect on both delta6 and delta5 desaturation indexes, either. On the other hand, sesamin significantly reduced the index of delta5 desaturation but not delta6 desaturation. These results suggested that sesamin reduced the delta5 desaturation index without the changing of the delta5 desaturase mRNA level.

Topics: 8,11,14-Eicosatrienoic Acid; Animals; Capsaicin; Cells, Cultured; Delta-5 Fatty Acid Desaturase; Dioxoles; Fatty Acid Desaturases; Gene Expression; Hepatocytes; Lignans; Linoleic Acid; Linoleoyl-CoA Desaturase; Male; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

We previously demonstrated the preventive effect of sesamin, a lignan from sesame oil, on the development of several experimental models of hypertension. In the present study, we explored the mechanisms underlying the antihypertensive effect of sesamin using the deoxycorticosterone acetate (DOCA)-salt rat hypertensive model. After a 5-week treatment period, aortic superoxide (O2-) production was measured in the lucigenin chemiluminescence assay. Chemiluminescence signals significantly decreased in sesamin-containing diet-fed DOCA-salt hypertensive rats compared with those in the normal diet-fed DOCA-salt rats, although the signals in sham-operated control animals were not affected by the sesamin feeding. In addition, there was a positive correlation between systolic blood pressure and aortic O2- production. These findings suggest that sesamin feeding inhibits enhanced vascular O2- production in DOCA-salt hypertensive rats and that the antioxidative action of sesamin may contribute to its antihypertensive activity.

Topics: Animals; Antihypertensive Agents; Aorta, Thoracic; Dioxoles; Hypertension; Lignans; Male; Rats; Rats, Sprague-Dawley; Superoxides

To establish a method for determining the content of L-sesamin and L-asarinin indifferent parts of Zanthoxylum(Roxb.)DC.. High-performance liquid chromatography (HPLC) was utilized for this purpose with the column of HYPERSIL BDS C18 and the mobile phase containing acetonitrile and water (50:50), the detection wavelength being 287 nm.. The average recovery rates for L-sesamin and L-asarinin were 100.13% and 1.61% and their relative standard deviation (RSD) were 101.24% and 1.46% respectively.. The method can be used for the quality control of Zanthoxylum(Roxb.)DC, and the roots of this herb contains more L-sesamin and L-asarinin than its other parts do.

Topics: Chromatography, High Pressure Liquid; Dioxoles; Drugs, Chinese Herbal; Lignans; Plants, Medicinal; Zanthoxylum

The effects of a combination of dietary conjugated linoleic acid (CLA) supplemented with sesamin on hepatic ketogenesis and triacylglycerol secretion were compared using the livers of rats fed diets containing 1% CLA or linoleic acid (LA) in combination with 0.2% sesamin for 14 d, respectively. The feeding of CLA, as compared to LA, caused a significant reduction in the weight of perirenal adipose tissue but not that of epididymal adipose tissue, and affected neither growth parameters nor hepatic lipid concentration. Hepatic production of ketone bodies was consistently higher in rats fed CLA than in those fed LA, while triacylglycerol secretion was reversed. No significant difference was noted in the hepatic secretion of cholesterol among the groups. Although there was no effect of the dietary combination of CLA with sesamin on adipose tissue weight, hepatic lipid parameters and ketone body production were observed: i.e., triacylglycerol secretion tended to be reduced. These results suggest that the dietary combination of CLA with sesamin may be an effective approach for lowering serum triacylglycerol levels. The decreased hepatic secretion of triacylglycerol is, in part, due to enhanced fatty acid oxidation in the liver.

Topics: Animals; Anticholesteremic Agents; Body Composition; Diet; Dioxoles; Ketone Bodies; Lignans; Linoleic Acid; Lipid Metabolism; Liver; Male; Perfusion; Rats; Rats, Sprague-Dawley; Time Factors; Triglycerides; Weight Gain

Intramolecular radical cyclization of suitably substituted epoxy ethers 4a-g using bis(cyclopentadienyl)titanium(III) chloride as the radical source resulted in trisubstituted tetrahydrofurano lignans and 2,6-diaryl-3,7-dioxabicyclo[3.3.0]octane lignans depending on the reaction conditions. The titanium(III) species was prepared in situ from commercially available titanocene dichloride and activated zinc dust in THF. Upon radical cyclization followed by acidic workup, epoxy olefinic ethers 4a-g afforded furano lignans dihydrosesamin 1a, lariciresinol dimethyl ether 1b, acuminatin methyl ether 1e, and sanshodiol methyl ether 1g directly and lariciresinol 1h, acuminatin 1i, and lariciresinol monomethyl ether 1j after removal of the benzyl protecting group by controlled hydrogenolysis of the corresponding cyclized products. The furofuran lignans sesamin 2a, eudesmin 2b, and piperitol methyl ether 2e were also prepared directly by using the same precursors 4a-f on radical cyclization followed by treatment with iodine and pinoresinol 2h, piperitol 2i, and pinoresinol monomethyl ether 2j after controlled hydrogenolysis of the benzyl protecting group of the corresponding cyclized products. Two naturally occurring acyclic lignans, secoisolariciresinol 5h and secoisolariciresinol dimethyl ether 5b, have also been prepared by exhaustive hydrogenolysis of 2h and 2b, respectively.

Topics: Alkylation; Catalysis; Chemistry, Organic; Cyclization; Dioxoles; Epoxy Compounds; Ethers, Cyclic; Flavonoids; Furans; Glycosides; Lignans; Lignin; Magnetic Resonance Spectroscopy; Molecular Structure; Stereoisomerism

The chemical constituents of the herb of Cuscuta chinensis Lam. were investigated. Five compounds were isolated from petroleum ether and chloroform fraction. Their structures were identified as beta-sitosterol, d-sesamin, 9(R)-hydroxy-d-sesamin, d-pinoresinol and daucosterol by chemical and spectroscopical methods. All these compounds were isolated from the stem for the first time.

Topics: Chemical Fractionation; Cuscuta; Dioxoles; Drugs, Chinese Herbal; Furans; Lignans; Sitosterols; Spectrum Analysis

Sesamin, a major lignan of Piper mullesua of Manipur origin, exhibited significant antifeedant activity and moderate growth inhibition towards 4th instar larvae of Spilarctia obliqua. No larval toxicity of sesamin could be established in topical bioassay experiments. Its effective dose for 50% feeding deterrence (ED(50)) and growth inhibition (GI(50)) were found to be 3856 and 6212 ppm, respectively.

Topics: Animals; Dioxoles; Growth Inhibitors; Insecticides; Larva; Lepidoptera; Lignans

Activities of enzymes involved in hepatic fatty acid oxidation and synthesis among rats fed sesame (Sesamum indicum L.) differing in lignan content (sesamin and sesamolin) were compared. Sesame seeds rich in lignans from two lines, 0730 and 0732, lines established in this laborary, and those from a conventional cultivar (Masekin) were employed. Seeds from the 0730 and 0732 lines contained sesamin and sesamolin at amounts twice those from Masekin. Sesame seeds were added at levels of 200 g/kg to the experimental diets. Sesame increased both the hepatic mitochondrial and the peroxisomal fatty acid oxidation rate. Increases were greater with sesame rich in lignans than with Maskin. Noticeably, peroxisomal activity levels were >3 times higher in rats fed diets containing sesame seeds from the 0730 and 0732 lines than in those fed a control diet without sesame. The diet containing Masekin seed caused only a 50% increase in the value, however. Diets containing seeds from the 0730 and 0732 lines, compared to the control and Masekin diets, also significantly increased the activity of hepatic fatty acid oxidation enzymes including acyl-CoA oxidase, carnitine palmitoyltranferase, 3-hydroxyacyl-CoA dehydrogenase, and 3-ketoacyl-CoA thiolase. In contrast, diets containing sesame lowered the activity of enzymes involved in fatty acid synthesis including fatty acid synthase, glucose-6-phosphate dehydrogenase, ATP-citrate lyase, and pyruvate kinase. No significant differences in enzyme activities were, however, seen among diets containing sesame from Masekin cultivar and lines 0730 and 0732. Serum triacylglycerol concentrations were lower in rats fed diets containing sesame from lines 0730 and 0732 than in those fed the control or Masekin diet. It is apparent that sesame rich in lignans more profoundly affects hepatic fatty acid oxidation and serum triacylglycerol levels. Therefore, consumption of sesame rich in lignans results in physiological activity to alter lipid metabolism in a potentially beneficial manner.

Topics: Animals; Antioxidants; Dioxoles; Fatty Acids; Lignans; Lipids; Liver; Male; Mitochondria, Liver; Oxidation-Reduction; Peroxisomes; Rats; Rats, Sprague-Dawley; Seeds

The effects of dietary sesamin on the hepatic metabolism of arachidonic (AA) and eicosapentaenoic (EPA) acids, were investigated with respect to their beta-oxidation and secretion as triacylglycerol (TG). For 2 wk, rats were fed three types of dietary oils: (i) corn oil (control) group; (ii) EPA group: EPA ethyl esters/rapeseed oil = 2:3; (iii) AA group: AA ethyl esters/palm oil/perilla oil = 2:2:1, with or without 0.5% (w/w) of sesamin. Dietary sesamin significantly increased the activities of hepatic mitochondrial and peroxisomal fatty acid oxidation enzymes (mitochondrial carnitine acyltransferase I, acyl-CoA dehydrogenase, and peroxisomal acyl-CoA oxidase). Dietary EPA increased mitochondrial carnitine acyltransferase I and peroxisomal acyl-CoA oxidase. Dietary AA, however, had an effect on peroxisomal acyl-CoA oxidase only. In whole liver and the TG fraction, EPA and AA concentrations were significantly increased by dietary EPA and AA, respectively, and were decreased by dietary sesamin. In hepatic mitochondria and peroxisomes, EPA concentration was increased by dietary EPA, but AA was not changed by dietary AA. The addition of dietary sesamin to the EPA-supplemented diet significantly decreased the EPA concentration compared to concentrations found with consumption of dietary EPA alone. These results suggest that sesamin increased beta-oxidation enzyme activities and reduced hepatic EPA and AA concentrations by degradation. The stimulating effect of sesamin on beta-oxidation, however, was more significant in the EPA group than in the AA group. Hepatic AA concentration was altered by the joint effect of sesamin through esterification into TG and the stimulation of beta-oxidation.

Topics: Animals; Arachidonic Acid; Body Weight; Chromatography, Thin Layer; Dioxoles; Eicosapentaenoic Acid; Feeding Behavior; Lignans; Liver; Male; Mitochondria, Liver; Organ Size; Oxidation-Reduction; Peroxisomes; Rats; Rats, Wistar

A series of novel 5-aryl-4-aryloxymethyl-3-diazotetrahydrofuran-2-ones (12, 24, and 35a/b) have been prepared and found to undergo regio- and stereoselective C-H insertion reactions to afford 2,6-diaryl-3,7-dioxabicyclo[3.3.0]octane-8-ones (18, 26, and 36a/b) with endo,exo stereochemistry. Subsequent reduction of the lactone ring and cyclization of the resulting diols 27 and 37a/b permitted the synthesis of three endo,exo-furofuran lignans: asarinin (2), fargesin (3), and epimagnolin A (4). En route to the key diazo compounds 24 and 35a/b, a modified procedure for the Ghosez keteniminium-olefin cyclization was developed, which was required to minimize the decomposition of acid-sensitive functional groups such as electron-rich benzylic ethers that were present in the target compounds 2-4.

Topics: Anti-Allergic Agents; Anticholesteremic Agents; Antihypertensive Agents; Antineoplastic Agents; Antioxidants; Dioxoles; Drugs, Chinese Herbal; Furans; Lignans; Lignin; Platelet Aggregation Inhibitors

The tocopherols, the major vitamers of vitamin E, are believed to play a role in the prevention of human aging-related diseases such as cancer and heart disease, yet little is known concerning determinants of their plasma concentrations. Evidence from animal studies suggests that the dietary source of gamma-tocopherol can significantly affect plasma levels of this tocopherol as well as its functional vitamin E activity. To determine whether plasma levels of tocopherols in humans are similarly altered, a study was undertaken in which subjects (n = 9) were fed muffins containing equivalent amounts of gamma-tocopherol from sesame seeds, walnuts, or soy oil. We observed that consumption of as little as 5 mg of gamma-tocopherol per day over a three-day period from sesame seeds, but not from walnuts or soy oil, significantly elevated serum gamma-tocopherol levels (19.1% increase, p = 0.03) and depressed plasma beta-tocopherol (34% decrease, p = 0.01). No significant changes in baseline or postintervention plasma levels of cholesterol, triglycerides, or carotenoids were seen for any of the intervention groups. All subjects consuming sesame seed-containing muffins had detectable levels of the sesame lignan sesamolin in their plasma. Consumption of moderate amounts of sesame seeds appears to significantly increase plasma gamma-tocopherol and alter plasma tocopherol ratios in humans and is consistent with the effects of dietary sesame seeds observed in rats leading to elevated plasma gamma-tocopherol and enhanced vitamin E bioactivity.

Topics: Adult; Aging; Antioxidants; Bread; Chromatography, High Pressure Liquid; Dioxoles; Female; Food Analysis; gamma-Tocopherol; Humans; Lignans; Male; Middle Aged; Nuts; Seeds; Sesame Oil; Soybean Oil; Tocopherols

The effect of sesamin, one of the most abundant lignans in sesame seed, on hepatic fatty acid synthesis was examined in rats. Rats were fed experimental diets containing varying amounts (0, 0.1 and 0.2% for Exp. 1 and 0, 0.2 and 0.4% for Exp. 2, respectively) of sesamin for 15 days. The activity and gene expression of enzymes involved in fatty acid synthesis including acetyl-CoA carboxylase, fatty acid synthase, ATP-citrate lyase and glucose-6-phosphate dehydrogenase decreased as the dietary level of sesamin increased in Exp. 1 and in rats fed the 0.2% sesamin diet they were approximately one-half those in animals fed a sesamin-free diet. In Exp. 2, the 0.2% sesamin diet lowered these parameters to one-half the level for a sesamin-free diet, but no further reduction was seen in animals fed the 0.4% sesamin diet. Dietary sesamin dose-dependently decreased the sterol regulatory element binding protein-1 (SREBP-1) mRNA level, and the value in rats fed a 0.4% sesamin diet was approximately one-half that in those fed a sesamin-free diet. The protein content of the membrane-bound precursor form of SREBP-1 decreased as dietary sesamin increased and was 37% lower in rats fed the 0.4% sesamin diet than in those fed a sesamin-free diet. Dietary sesamin exerted a more marked influence on the protein content of the mature nuclear form of SREBP-1. Diets containing 0.2 and 0.4% sesamin lowered the amount of mature SREBP-1 protein to less than one-fifth of that in the animals fed a sesamin-free diet. It was suggested that the dietary sesamin-dependent decrease in lipogenic enzyme gene expression is due to the suppression of the gene expression of SREBP-1 as well as the proteolysis of the membrane-bound precursor form of this transcriptional factor to generate the mature form.

Topics: Acetyl-CoA Carboxylase; Animals; ATP Citrate (pro-S)-Lyase; Blotting, Western; CCAAT-Enhancer-Binding Proteins; Cholesterol; Dioxoles; DNA-Binding Proteins; Down-Regulation; Fatty Acid Synthases; Fatty Acids; Gene Expression Regulation, Enzymologic; Glucosephosphate Dehydrogenase; Lignans; Liver; Male; Rats; Rats, Sprague-Dawley; Receptors, LDL; RNA, Messenger; Sterol Regulatory Element Binding Protein 1; Transcription Factors

The preventive effects of sesamin, a lignan from sesame oil, and vitamin E on hypertension and thrombosis were examined using stroke-prone spontaneously hypertensive rats (SHRSP). At 5 weeks of age the animals were separated into four groups: (i) a control group; (ii) a vitamin E group, which was given a 1,000 mg alpha-tocopherol/kg diet; (iii) a sesamin group, given a 1,000 mg sesamin/kg diet; and (iv) a vitamin E plus sesamin group, given a 1,000 mg alpha-tocopherol plus 1,000 mg sesamin/kg diet for 5 weeks from 5 to 10 weeks of age. Resting blood pressure was measured by the tail-cuff method once weekly. A closed cranial window was created and platelet-rich thrombi were induced in vivo using a helium-neon laser technique. The number of laser pulses required for formation of an occlusive thrombus was used as an index of thrombotic tendency. In control rats, systolic blood pressure and the amount of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) became significantly elevated with age. However, the elevation in blood pressure and 8-OHdG were significantly suppressed in rats administrated vitamin E, sesamin, or vitamin E plus sesamin. At 10 weeks, the number of laser pulses required to induce an occlusive thrombus in arterioles of the control group was significantly lower than in the other groups (p<0.05). These results indicate that chronic ingestion of vitamin E and sesamin attenuated each of elevation in blood pressure, oxidative stress and thrombotic tendency, suggesting that these treatments might be beneficial in the prevention of hypertension and stroke.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Blood Pressure; Blood Vessels; Body Weight; Cerebrovascular Circulation; Cerebrovascular Disorders; Deoxyguanosine; Dioxoles; Disease Susceptibility; Drug Combinations; Genetic Predisposition to Disease; Hypertension; Lignans; Male; Microcirculation; Rats; Rats, Inbred SHR; Stroke; Thrombosis; Vasomotor System; Vitamin E

To study whether the body fat-reducing potential of conjugated linoleic acid (CLA) could be increased through dietary manipulations, the effects of the combination of CLA with different proteins, fats, and sesamin were examined in rats. Male rats were fed diets containing 1% CLA or linoleic acid (LA) in combination with different proteins (20% of casein or soybean protein), fats (7% perilla oil or soybean oil) and 0.2% sesamin (SES) for 3 or 4 weeks. When the dietary fat source was soybean oil, CLA, as compared with LA, significantly reduced weights of epididymal and perirenal adipose tissues, irrespective of the dietary protein sources. However, the highest reducing effect was shown when soybean protein was given as a protein source. SES stimulated the reduction of epididymal and perirenal adipose tissue weights in both protein diets. In contrast, CLA increased the weight of brown adipose tissue, and SES further increased it in combination with soybean oil but not with perilla oil. No effect of dietary manipulation was observed on serum leptin and TNF-alpha levels. Thus, the body fat-reducing potential of CLA can be increased by an appropriate combination with food factors that may stimulate fatty acid beta-oxidation.

Topics: Adipose Tissue; Adipose Tissue, Brown; Animals; Diet, Reducing; Dietary Fats, Unsaturated; Dietary Proteins; Dioxoles; Leptin; Lignans; Linoleic Acids; Lipids; Male; Organ Size; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

Docosahexaenoic acid (DHA) is an essential nutrient for human health, but has extremely high oxidative susceptibility. We examined the suppressing effect of sesamin, a sesame seed lignan, on lipidperoxides in rats fed a low alpha-tocopherol and high DHA containing diet. Groups of rats were fed four experimental diets: low alpha-tocopherol (10 mg/kg diet) control diet, low alpha-tocopherol + 0.2% sesamin diet, low alpha-tocopherol + 0.5% DHA diet and low alpha-tocopherol + 0.5% DHA + 0.2% sesamin diet. TBARS concentrations in plasma and liver were significantly increased by DHA, but were completely suppressed by sesamin. Alpha-tocopherol concentrations in plasma and liver decreased by addition of DHA, but with sesamin recovered to the control level. The addition of DHA into the diets caused remarkable increases of DHA concentrations in plasma and liver lipids. Sesamin caused a significant increase of DHA concentrations in the triacylglycerol of plasma.

Topics: Animals; Antioxidants; Dietary Fats, Unsaturated; Dioxoles; Docosahexaenoic Acids; Drug Synergism; Hemolysis; Lignans; Lipid Peroxidation; Lipid Peroxides; Liver; Rats; Triglycerides; Vitamin E

The exposure of human lymphoid leukemia Molt 4B cells to sesamin and episesamin which were isolated from unroasted sesame seed oil and identified by MS, and 1H and 13C-NMR, led to both growth inhibition and the induction of programmed cell death (apoptosis). Morphological change showing apoptotic bodies was observed in the Molt 4B cells treated with sesamin and episesamin. The fragmentations by sesamin and episesamin of DNA to oligonucleosomal-sized fragments that are characteristics of apoptosis were observed to be concentration-dependent, respectively. Moreover, the amount of the DNA fragments in the sesamin-treated cells was increased from 2 days, while that in the episesamin-treated cells was elevated at 3 days after addition of the compounds. These findings suggest that growth inhibitions by sesamin and episesamin of Molt 4B cells result from the induction of apoptosis in the cells.

Topics: Antineoplastic Agents; Apoptosis; Dioxoles; DNA Fragmentation; Humans; Leukemia, Lymphoid; Lignans; Magnetic Resonance Spectroscopy; Mass Spectrometry; Microscopy, Fluorescence; Sesame Oil; Tumor Cells, Cultured

The effects of the phenolic compounds butylated hydroxytoluene (BHT), sesamin (S), curcumin (CU), and ferulic acid (FA) on plasma, liver, and lung concentrations of alpha- and gamma-tocopherols (T), on plasma and liver cholesterol, and on the fatty acid composition of liver lipids were studied in male Sprague-Dawley rats. Test compounds were given to rats ad libitum for 4 wk at 4 g/kg diet, in a diet low but adequate in vitamin E (36 mg/kg of gamma-T and 25 mg/kg of alpha-T) and containing 2 g/kg of cholesterol. BHT significantly reduced feed intake (P < 0.05) and body weight and increased feed conversion ratio; S and BHT caused a significant enlargement of the liver (P < 0.001), whereas CU and FA did not affect any of these parameters. The amount of liver lipids was significantly lowered by BHT (P < 0.01) while the other substances reduced liver lipid concentrations but not significantly. Regarding effects on tocopherol levels, (i) feeding of BHT resulted in a significant elevation (P< 0.001) of alpha-T in plasma, liver, and lung, while gamma-T values remained unchanged; (ii) rats provided with the S diet had substantially higher gamma-T levels (P < 0.001) in plasma, liver, and lung, whereas alpha-T levels were not affected; (iii) administration of CU raised the concentration of alpha-T in the lung (P < 0.01) but did not affect the plasma or liver values of any of the tocopherols; and (iv) FA had no effect on the levels of either homolog in the plasma, liver, or lung. The level of an unknown substance in the liver was significantly reduced by dietary BHT (P < 0.001). BHT was the only compound that tended to increase total cholesterol (TC) in plasma, due to an elevation of cholesterol in the very low density lipoprotein + low density lipoprotein (VLDL + LDL) fraction. S and FA tended to lower plasma total and VLDL + LDL cholesterol concentrations, but the effect for CU was statistically significant (P < 0.05). FA increased plasma high density lipoprotein cholesterol while the other compounds reduced it numerically, but not significantly. BHT, CU, and S reduced cholesterol levels in the liver TC (P < 0.001) and percentages of TC in liver lipids (P < 0.05). With regard to the fatty acid composition of liver lipids, S increased the n-6/n-3 and the 18:3/20:5 polyunsaturated fatty acids (PUFA) ratios, and BHT lowered total monounsaturated fatty acids and increased total PUFA (n-6 + n-3). The effects of CU and FA on fatty acids were not highly significant. Thes

Topics: Animals; Butylated Hydroxytoluene; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Coumaric Acids; Curcumin; Diet; Dioxoles; Fatty Acids; Lignans; Liver; Lung; Male; Phenols; Rats; Rats, Sprague-Dawley; Vitamin E

Sesamin, a nonfat constituent of sesame oil, inhibits Delta(5)-desaturase activity, resulting in accumulation of dihomo-gamma-linolenic acid (DGLA), which displaces arachidonic acid (AA) and consequently decreases the formation of proinflammatory 2-series prostaglandins.. We sought to determine whether dietary supplementation with sesamin augments the antiinflammatory effects of dietary linseed oil in rats.. We investigated the effects of continuous tube feedings of emulsions containing safflower oil or linseed oil with sesamin (SO+ and LO+) or without sesamin (SO and LO) on liver fatty acid composition and on endotoxin-induced production of prostaglandin E(2), 6-keto-prostaglandin F(1alpha), and tumor necrosis factor alpha (TNF-alpha) by whole blood from rats (n = 6 per diet group).. We found a significant accumulation of DGLA only in the liver phospholipids of animals fed SO+ and LO+ (1.8 +/- 0.2 and 1.4 +/- 0.3 mol%, respectively), which suggests that sesamin inhibited Delta(5)-desaturation of n-6 fatty acids. These changes were associated with significant reductions in plasma prostaglandin E(2) concentrations in animals fed SO+ compared with those fed SO (P: < 0. 05). Despite a significant reduction in tissue AA content in the LO group, the prostaglandin E(2) concentrations did not differ significantly from those of the SO group. Plasma concentrations of TNF-alpha were significantly lower (P: < 0.05) in the animals fed LO+ than in those fed SO (199 +/- 48 and 488 +/- 121 ng/L, respectively).. These data indicate that in rats, tube feedings of diets containing sesamin exerted antiinflammatory effects that were augmented by concurrent consumption of linseed oil.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Inflammatory Agents; Body Weight; Dietary Fats; Dietary Supplements; Dinoprostone; Dioxoles; Emulsions; Fatty Acids; Lignans; Lipopolysaccharides; Liver; Male; Prostaglandins; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

The effect of sesamin, a lignan from sesame oil, on altered vasodilator and vasoconstrictor responses in aortic rings from deoxycorticosterone acetate (DOCA)-salt-induced hypertensive rats, were examined. The systolic blood pressure after 5-weeks DOCA-salt treatment was 195.0+/-2.8 mmHg, which was much higher than that of sham-operated control animals (131.2+/-2.4 mmHg). Sesamin feeding significantly suppressed the development of this hypertension (167.1+/-8.6 mmHg). Acetylcholine (ACh)-induced endothelium-dependent relaxation of aortic rings was markedly decreased in the DOCA-salt hypertensive animals, compared with cases of the control (pD2, 7.0+/-0.1; maximal response, 64.8+/-3.4% versus pD2, 7.7+/-0.2; maximal response, 93.3+/-2.7%). These changes were partially but significantly improved by the sesamin feeding. This improvement seems to be related to a nitric oxide (NO)-dependent component of ACh-induced action, because sesamin feeding did not affect the responses to ACh in the presence of NO synthase inhibitor. A spontaneous NO releaser (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (NOR 3) which exerts endothelium-independent vasodilatation, produced the same patterns of responses as those observed with ACh in cases of DOCA-salt treatment and sesamin feeding. Phenylephrine-induced vasoconstriction was enhanced by the DOCA-salt treatment, both in preparations with and without endothelium, but these enhancements were almost completely normalized by sesamin feeding. Thus, dietary sesamin could efficiently improve the abnormal vasodilator and vasoconstrictor responses in DOCA-salt hypertensive animals. These effects may contribute to the antihypertensive activity of sesamin.

Topics: Animals; Antihypertensive Agents; Aorta; Body Weight; Desoxycorticosterone; Diet; Dioxoles; Hypertension; In Vitro Techniques; Lignans; Male; Nitric Oxide; Rats; Rats, Sprague-Dawley; Sodium Chloride; Vasoconstriction

Carboxychroman metabolites of the major dietary tocopherols are excreted in human urine, but the mechanism of their synthesis is unknown. We employed well-characterized inhibitors of specific cytochrome P-450 (CYP) enzymes to determine which form was likely involved in tocopherol side chain oxidation. Ketoconozole (1.0 microM), a potent and selective inhibitor of CYP3A, substantially inhibited metabolism of gamma- and alpha-tocopherol in rat primary hepatocytes, and metabolism of gamma- and delta-tocopherol in HepG2/C3A cells. Sulphaphenazole and cyclosporin, inhibitors of CYP2C and CYP27, respectively, were without effect. Sesamin, a sesame lignan that causes elevation of tissue tocopherol concentration in rats, strongly inhibited tocopherol metabolism by HepG2/C3A cells at 1.0 microM. These results support a CYP3A-dependent mechanism of side chain metabolism of tocopherols to water-soluble carboxychromans, and provide the first evidence of a specific enzyme involved in vitamin E metabolism. The data further suggest that sesamin increases tissue tocopherol concentration by inhibiting tocopherol catabolism.

Topics: Antioxidants; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Dioxoles; Enzyme Inhibitors; Humans; Isoenzymes; Ketoconazole; Lignans; Liver; Oxidation-Reduction; Oxidoreductases, N-Demethylating; Tumor Cells, Cultured; Vitamin E

3,5-Dimethoxy-4-geranyloxycinnamyl alcohol (1), 8-methoxy-N-methylflindersine (2), xanthyletin and sesamin have been isolated from petroleum ether extract of the stem bark of Zanthoxylum rhesta. The petroleum ether extract and 8-methoxy-N-methylflindersine showed cytotoxicity on brine shrimp nauplii.

Topics: Animals; Artemia; Coumarins; Dioxoles; Humans; Lignans; Plant Extracts; Plant Stems; Plants, Medicinal; Pyrans; Quinolones

The filamentous fungus, Mortierella alpina, accumulates complex lipids relatively rich in arachidonic acid (C(20:4) Delta(5,8,11,14)). The lignan, sesamin, has been used to reduce arachidonic acid production by specifically inhibiting Delta(5)-desaturation [Shimizu, Akimoto, Shinmen, Kawashima, Sugano and Yamada (1991) Lipids 26, 512-516]. Microsomal membrane preparations from M. alpina exhibit acyl-CoA:1-acyl lysophosphatidylcholine acyltransferase (LPCAT) activity. LPCAT is an enzyme involved in channelling fatty acid substrates to phosphatidylcholine for subsequent desaturation. Sesamin was found to inhibit this enzyme as measured in both spectrophotometric and radioactive assays. The inhibitory effect of sesamin on LPCAT was only evident in species of Mortierella and could not be demonstrated in other organisms.

Topics: 1-Acylglycerophosphocholine O-Acyltransferase; Antioxidants; Dioxoles; Intracellular Membranes; Kinetics; Lignans; Microsomes; Mucorales; Sesame Oil

The effects of six lignans and neolignans as inhibitors of ecdysis and on the water balance in fourth-instar larvae of Rhodnius prolixus were studied by oral, topical and continuous contact treatments. The main results may be summarised as follows: (i) burchellin, pinoresinol, sesamin, licarin A and nordihydroguaiaretic acid (NDGA) did not cause feeding inhibition at doses of 100 micrograms/ml blood; podophyllotoxin had no antifeedant effect but caused a high moulting inhibition and significant toxicity when applied either orally or topically; (ii) the highest ecdysis inhibitory effects were observed with pinoresinol and NDGA when applied orally at a dose of 100 micrograms/ml (58% and 50% of moulting inhibition, respectively); burchellin inhibited 30% of the moulting at this concentration; (iii) by topical treatment none of the compounds presented any influence on the moulting cycle; and (iv) podophyllotoxin and burchellin significantly reduced the excretion of the insect in 24 h; the other compounds had no effect on excretion. The implications of these findings in relation to the pertinent biological events in R. prolixus are discussed.

Topics: Animals; Benzofurans; Dioxoles; Feeding Behavior; Furans; Larva; Lauraceae; Lignans; Masoprocol; Plants, Medicinal; Podophyllotoxin; Rhodnius

In this study, we examined the distribution and metabolism of refined sesame oil lignans (sesamin and episesamin) in rat. For 8 wk rats were fed the diet including 0.5% (w/w) sesame lignans (sesamin and episesamin) with 5% (w/w) corn oil or eicosapentaenoic acid (EPA)-rich oil. The concentrations of sesamin and episesamin in rat liver after their administration for 8 wk were very low; both of them were less than 0.5 microgram/g liver. These were observed in both oil groups although the fatty acid compositions of dietary oils were completely different. No significant difference existed in lymphatic absorption between sesamin and episesamin. To investigate the distribution of sesamin and episesamin in rats, the concentrations of sesamin and episesamin were determined in tissues and serum within 24 h after administration to rats. Sesamin and episesamin may be, at first, incorporated into the liver and then transported to the other tissues (lung, heart, kidney, and brain). They are lost from the body within 24 h after administration. There was no significant difference in lymphatic absorption between sesamin and episesamin, but the amount of sesamin was significantly lower than that of episesamin in all tissues and serum. These results suggest that sesamin is absorbed in lymph the same as episesamin, but that sesamin is subsequently metabolized faster by the liver.

Topics: Animals; Brain; Dioxoles; Kidney; Lignans; Liver; Lung; Lymph; Male; Myocardium; Rats; Rats, Wistar; Tissue Distribution

Plant glucosides possess antioxidative properties due to their ability to scavenge free radicals. Sesame seeds contain a class of these compounds, the sesaminol glucosides. To evaluate their antioxidative activity in vivo, we fed rabbits diets containing 1% cholesterol (Chol) with or without 10% defatted sesame flour (DSF) (containing 1% sesaminol glucosides) for 90 d. We determined the susceptibility of their tissues to oxidation ex vivo as well as serum total cholesterol (TC), phospholipid (PL), triglyceride (TG) and HDL cholesterol (HDL-C) concentrations. Serum TC, HDL-C, PL and TG levels were unaffected by the addition of DSF. The HDL-C in the Chol + DSF group was greater than in the Chol group at 45 d. Both were greater than in the groups that did not consume cholesterol. Liver TC and TG were significantly lower in rabbits fed the diet containing DSF plus 1% cholesterol than in those fed 1% cholesterol alone. Lipid peroxidation activity, measured as 2-thiobarbituric acid reactive substances (TBARS), was lower in the liver (P < 0.05) and serum (P = 0.06) of rabbits fed DSF plus cholesterol than in rabbits fed the cholesterol diet. Although we did not detect sesaminol glucosides in peripheral tissues, we observed abundant quantities of sesaminol in rabbits fed DSF, the principal metabolite. Our findings suggest that feeding DSF to rabbits does not protect cholesterol-induced hypercholesterolemia, but may decrease susceptibility to oxidative stress in rabbits fed cholesterol, perhaps due to the antioxidative activity of sesaminol.

Topics: Analysis of Variance; Animals; Anticholesteremic Agents; Antioxidants; Body Weight; Cholesterol, Dietary; Cholesterol, LDL; Chromatography, High Pressure Liquid; Dietary Fats; Dioxoles; Flour; Furans; Hypercholesterolemia; Lignans; Lipid Peroxidation; Liver; Male; Organ Size; Oxidative Stress; Rabbits; Vitamin E

The effects of sesamin, one of the most abundant lignans in sesame seed, on hepatic fatty acid oxidation were examined in rats that were fed experimental diets containing various amounts (0%, 0.1%, 0.2%, and 0.5%) of sesamin (a 1:1 mixture of sesamin and episesamin) for 15 days. Dietary sesamin dose-dependently increased both mitochondrial and peroxisomal palmitoyl-coenzyme A (CoA) oxidation rates. Mitochondrial activity almost doubled in rats on the 0.5% sesamin diet. Peroxisomal activity increased more than 10-fold in rats fed a 0.5% sesamin diet in relation to rats on the sesamin-free diet. Dietary sesamin greatly increased the hepatic activity of fatty acid oxidation enzymes, including carnitine palmitoyltransferase, acyl-CoA dehydrogenase, acyl-CoA oxidase, 3-hydroxyacyl-CoA dehydrogenase, enoyl-CoA hydratase, and 3-ketoacyl-CoA thiolase. Dietary sesamin also increased the activity of 2,4-dienoyl-CoA reductase and delta3,delta2-enoyl-CoA isomerase, enzymes involved in the auxiliary pathway for beta-oxidation of unsaturated fatty acids dose-dependently. Examination of hepatic mRNA levels using specific cDNA probes showed a sesamin-induced increase in the gene expression of mitochondrial and peroxisomal fatty acid oxidation enzymes. Among these various enzymes, peroxisomal acyl-CoA oxidase and bifunctional enzyme gene expression were affected most by dietary sesamin (15- and 50-fold increase by the 0.5% dietary level). Sesamin-induced alterations in the activity and gene expression of carnitine palmitoyltransferase I and acyl-CoA oxidase were in parallel with changes in the mitochondrial and peroxisomal palmitoyl-CoA oxidation rate, respectively. In contrast, dietary sesamin decreased the hepatic activity and mRNA abundance of fatty acid synthase and pyruvate kinase, the lipogenic enzymes. However, this lignan increased the activity and gene expression of malic enzyme, another lipogenic enzyme. An alteration in hepatic fatty acid metabolism may therefore account for the serum lipid-lowering effect of sesamin in the rat.

Topics: Administration, Oral; Animals; Antioxidants; Blood Glucose; Cholesterol; Dioxoles; DNA Primers; DNA Probes; Fatty Acids, Nonesterified; Gene Expression Regulation, Enzymologic; Lignans; Liver; Male; Mitochondria, Liver; Oxidation-Reduction; Palmitoyl Coenzyme A; Peroxisomes; Phospholipids; Rats; Rats, Sprague-Dawley; Triglycerides

To estimate the relative significance of exogenous and endogenous fatty acid substrates in decreasing hepatic triacylglycerol secretion after sesamin feeding, livers from rats fed diets supplemented with and without sesamin (sesamin: episesamin, 1:1, w/w) were perfused in the presence and absence of an exogenous di-trans isomer of linoleic acid (linolelaidic acid, trans,trans-9,12-octadecadienoic acid). Both exogenous trans fatty acid and dietary sesamin, as compared with respective controls, resulted in a marked increase in hepatic ketogenesis; however, the beta-hydroxybutyrate to acetoacetate ratio was elevated by exogenous fatty acid and decreased by dietary sesamin. On the other hand, hepatic secretions of triacylglycerol, phospholipid and cholesterol were markedly lowered in rats fed sesamin, especially when exogenous fatty acid substrate was provided. The relative significance of the exogenous fatty acid was observed in the dietary sesamin-induced decrease in hepatic secretion of triacylglycerol. These results suggest that increased fatty acid oxidation by dietary sesamin, as reflected by enhanced ketone body production, leads to decreased partition of fatty acid substrates to the esterification pathways, and this in turn reduces the synthesis and secretion of triacylglycerol. The altered metabolism of exogenous fatty acids in the liver was therefore a major determinant for the synthesis and secretion of triacylglycerol.

Topics: Animals; Diet; Dioxoles; Fatty Acids; Hypolipidemic Agents; Ketone Bodies; Lignans; Linoleic Acid; Lipid Metabolism; Liver; Male; Rats; Rats, Wistar; Triglycerides

Sesamin (a non-fat portion of sesame seed oil) inhibits delta-5 desaturase activity resulting in an accumulation of dihomo-gamma-linolenic acid (DGLA) which can displace arachidonic acid (AA) and decrease the formation of pro-inflammatory mediators. We investigated the effects of consumption of diets containing 0.25wt% sesamin and 15 wt% safflower oil (SO) (providing 12% of the added fat as linoleic acid) or a 15 wt% 2:1 mixture of linseed oil and SO (LOSO) (providing 6% alpha-linolenic acid and 6% linoleic acid) for 3 weeks on the liver membrane fatty acid composition and on the production of prostaglandin (PG) E2, TNF-alpha, IL-6 and IL10 in mice. Consumption of sesamin-supplemented SO and LOSO diets resulted in a significant increase in the levels of 20:3omega6 (DGLA), suggesting that sesamin inhibited delta-5 desaturation of omega6 fatty acids. In animals fed LOSO diets, the levels of alpha-linolenic acid, eicosapentaenoic acid (EPA) and of docosahexaenoic acid (DHA) were elevated with a concomitant decrease of arachidonic acid (AA) in the liver membrane phospholipids. Further, in animals fed LOSO diets with or without sesamin, an increase in the circulating levels of TNF-alpha was associated with a concomitant decrease in PGE2. Despite a lack of differences in the levels of AA, the PGE2 levels were significantly lower in mice fed sesamin-supplemented SO compared to those fed SO alone. Thus, these data suggest that irrespective of the availability of a specific fatty acid as a substrate, through regulating the PGE2 synthesis, the production of TNF-alpha could be modulated.

Topics: alpha-Linolenic Acid; Animals; Anticholesteremic Agents; Delta-5 Fatty Acid Desaturase; Dietary Fats, Unsaturated; Dinoprostone; Dioxoles; Dose-Response Relationship, Drug; Fatty Acid Desaturases; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Female; Interleukin-10; Interleukin-6; Lignans; Lipopolysaccharides; Membrane Lipids; Mice; Mice, Inbred BALB C; Tumor Necrosis Factor-alpha

The antihypertensive effect of sesamin, a lignan from sesame oil, was examined using salt-loaded and unloaded stroke-prone spontaneously hypertensive rats (SHRSP). The animals at 6 weeks of age were separated into a salt-loaded group and an unloaded group. Salt-loaded animals were maintained on 1% NaCl drinking water. Each group was further divided into two groups: normal-diet group and sesamin-diet group. Systolic blood pressure of all animals was monitored once weekly. At the end of the feeding periods, cardiovascular hypertrophy and renal damage were evaluated. In the salt-loaded group, sesamin feeding significantly suppressed the development of hypertension, and efficient suppression was maintained from 9 to 26 weeks (e.g., 215+/-4 vs. 180+/-4 mmHg, at 17 weeks old). The left ventricle plus septum weight-to-body weight ratio was slightly but significantly lowered by sesamin feeding. When the degree of vascular hypertrophy of the aorta and superior mesenteric artery was histochemically evaluated, wall thickness and wall area of these vessels were significantly decreased by the sesamin feeding. Histological renal damage such as thickening of the tunica intima and fibrinoid degeneration of the arterial wall were often observed in the normal-diet group, but this damage was efficiently reduced in the sesamin-fed animals. On the other hand, in the salt-unloaded group, only a slight and nonsignificant suppressive effect of sesamin on the development of hypertension was observed. Although the wall area of the aorta was significantly decreased by the sesamin feeding, other vascular parameters were not ameliorated. The incidence of histological renal damage tended to decrease in sesamin-fed animals, but these alterations were not statistically significant. Thus, sesamin feeding was much more effective as an antihypertensive regimen in salt-loaded SHRSP than in unloaded SHRSP, thereby suggesting that sesamin is more useful as a prophylactic treatment in the malignant status of hypertension and/or hypertension followed by water and salt retention.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Body Weight; Cardiomegaly; Cerebrovascular Disorders; Diet; Dioxoles; Heart Rate; Hypertension; Kidney; Kidney Diseases; Lignans; Male; Myocardium; Rats; Rats, Inbred SHR

In this study, we examined the effect of dietary arachidonic acid (AA) and sesame lignans on the content and n-6/n-3 ratio of polyunsaturated fatty acid (PUFA) in rat liver and the concentrations of triglyceride (TG) and ketone bodies in serum. For 4 wk, rats were fed two types of dietary oils: (i) the control oil diet groups (CO and COS): soybean oil/perilla oil = 5:1, and (ii) the AA-rich oil group (AO and AOS): AA ethyl esters/palm oil/perilla oil = 2:2:1, with (COS and AOS) or without (CO and AO) 0.5% (w/w) of sesame lignans. Dietary AA and sesame lignans significantly affected hepatic PUFA metabolism. AA content and n-6/n-3 ratio in the liver were significantly increased in the AO group, despite the dietary total of n-6 PUFA being the same in all groups, while AOS diet reduced AA content and n-6/n-3 ratio to a level similar to the CO and COS groups. These results suggest that (i) dietary AA considerably affects the hepatic profile and n-6/n-3 ratio of PUFA, and (ii) dietary sesame lignans reduce AA content and n-6/n-3 ratio in the liver. In the AO group, the concentration of acetoacetate was significantly increased, but the ratio of beta-hydroxybutyrate/acetoacetate was decreased. On the other hand, the AO diet increased the concentration of TG in serum by almost twofold as compared to other groups. However, the AOS diet significantly reduced serum TG level as compared to the AO group. In addition, the AOS diet significantly increased the acetoacetate level, but reduced the beta-hydroxybutyrate/acetoacetate ratio. These results suggest that dietary sesame lignans promote ketogenesis and reduce PUFA esterification into TG. This study resulted in two findings: (i) sesame lignans inhibited extreme changes of the n-6/n-3 ratio by reducing hepatic PUFA content, and (ii) the reduction of hepatic PUFA content may have occurred because of the effects of sesame lignans on PUFA degradation (oxidation) and esterification.

Topics: Animals; Arachidonic Acid; Dietary Fats, Unsaturated; Dioxoles; Fatty Acids, Essential; Fatty Acids, Unsaturated; Ketone Bodies; Lignans; Liver; Male; Rats; Rats, Wistar; Sesame Oil; Triglycerides

We examined the effect of three dietary fats, safflower oil (SAF) rich in linoleic acid, borage oil (BOR) rich in gamma-linolenic acid, and perilla oil (PER) rich in alpha-linolenic acid, on the lipid metabolism, and chemical mediator and immunoglobulin levels in Sprague-Dawley rats, as well as the dietary effect of sesame-derived antioxidative sesamin. The serum cholesterol, phospholipid, triglyceride, prostaglandin E2 level and splenic leukotriene B4 level were lower in the rats fed on BOR or PER than in those fed on SAF. SES feeding suppressed the expression of the lipid-decreasing effect of BOR, but not in the rats fed on PER. In respect of the fatty acid composition of the liver and spleen, PER feeding gave a lower arachidonic acid level, and higher eicosapentaenoic and docosahexaenoic acid levels than SAF feeding did, while the effect of BOR feeding was marginal. The effect of SES feeding on fatty acid composition was much smaller than that of dietary fats. In respect of immunoglobulin production, PER + SES feeding gave the lowest IgE productivity in the mesenteric lymph node lymphocytes. These results suggest that PER feeding regulated lipid metabolism and exerted an anti-allergic effect by a different mechanism from that with BOR feeding.

Topics: alpha-Linolenic Acid; Animals; Anticholesteremic Agents; Dietary Fats; Dioxoles; gamma-Linolenic Acid; Immunoglobulins; Lignans; Linoleic Acid; Lipids; Male; Plant Oils; Rats; Rats, Sprague-Dawley; Safflower Oil

The effects of dietary sesamin (a mixture of sesamin and episesamin, 1:1, w/w) on ketone body production and lipid secretion were studied in isolated perfused liver from rats given sesamin. Feeding sesamin at the dietary level of 0.2% from 14 to 16 d resulted in an enlargement of liver weight. Ketone body production was significantly elevated in the livers perfused with oleic acid in comparison with those perfused without an exogenous-free fatty acid, and sesamin feeding caused a stimulation of ketone body production, especially when exogenous oleic acid was provided. On the other hand, the ratio of beta-hydroxybutyrate to acetoacetate, an index of mitochondrial redox potential, tended to increase in the livers perfused with oleic acid compared with those without fatty acid, thought it was consistently lowered by dietary sesamin. The cumulative secretion of triacylglycerol, but not of cholesterol, by the livers from sesamin-fed rats was decreased markedly, especially when exogenous oleic acid was provided, suggesting an inverse relationship between the rates of ketogenesis and triacylglycerol secretion. These results suggest that dietary sesamin exerts its hypotriglyceridemic effect at least in part through an enhanced metabolism of exogenous-free fatty acid to oxidation at the expense of esterification in rat liver.

Topics: 3-Hydroxybutyric Acid; Acetoacetates; Animals; Antioxidants; Cholesterol; Diet; Dioxoles; Ketone Bodies; Kinetics; Lignans; Liver; Male; Oleic Acid; Organ Size; Rats; Rats, Wistar; Triglycerides

The effects of sesaminol and sesamin on the ethanol-induced modulation of immune indices related to food allergy were examined in rats given a low (10%)-casein diet. Chronic ethanol drinking, at the dietary level of 23% (w/w), significantly increased the plasma IgA and IgM concentrations, irrespective of the presence of 0.1% and 0.2% sesaminol, but the effects disappeared with 0.2% sesamin. A significant IgG-elevating effect of these lignans was also found. In contrast, the concentration of plasma IgE was not influenced by the dietary manipulation. Although ethanol drinking did not influence splenic leukotriene B4 production, sesaminol tended to decrease it dose dependently, while sesamin increased the plasma prostaglandin E2 concentration. These results suggest that sesaminol and sesamin seems to have a diverse effect on the plasma levels of immunoglobulins and eicosanoids.

Topics: Analysis of Variance; Animals; Diet; Dinoprostone; Dioxoles; Ethanol; Furans; Immunoglobulins; Leukotriene B4; Lignans; Male; Rats; Rats, Wistar; Sesame Oil; Spleen

Two lignans, asarinin (6) and xanthoxylol (7), were isolated from the radix of Asiasarum heterotropoides var. mandshuricum, which consist of a kampo prescription, Shouseiryu-to, as inhibitors of Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). These lignans also exhibited remarkable inhibitory effects on a two-stage carcinogenesis test of mouse skin and pulmonary tumors. Furthermore, it was confirmed that these hydrophobic lignans dissolved in the water decoction of Shouseiryu-to, and these lignans might be among the active constituents of this kampo prescription in terms of its anti-tumor-promoting activity.

Topics: Animals; Anticarcinogenic Agents; Antigens, Viral; Cell Line; Cell Transformation, Neoplastic; Dioxoles; Female; Furans; Lignans; Lung Neoplasms; Mice; Mice, Inbred ICR; Phenols; Skin Neoplasms; Tetradecanoylphorbol Acetate

Sesamin, present in sesame seed oil (SSO), can inhibit delta-5-desaturase activity and cause accumulation of dihomo-gamma-linolenic acid (DGLA), which displaces arachidonic acid, and subsequently decrease production of dienoic eicosanoids. The effects of diets containing both SSO and Quil A, a saponin that emulsifies fats and potentiates the immune responses, were also studied. A mixture of oils having a fatty-acid composition similar to that of SSO served as a control diet. The levels of docosapentaenoic acid in mice fed Quil-A-supplemented diets and of DGLA in those fed SSO diets were markedly higher in the liver. These changes were associated with a significant reduction in the plasma prostaglandin-E(1+2) and thromboxane-B2 levels in response to an intraperitoneal injection of a lethal dose of lipopolysaccharide (LPS) endotoxin (LD50 20 mg/kg). The levels of interleukin (IL-)6 were elevated and those of IL-1beta were decreased in mice consuming Quil-A-supplemented diets. The IL-10 levels that were elevated in all mice after LPS exposure, remained higher (even at 9 h) only in those fed Quil-A-supplemented diets, but declined rapidly in others. During a 48-hour observation period following LPS injection, all control animals died, and survival was 40% in the SSO group, and 27 and 50%, respectively, in those fed Quil-A-supplemented control and SSO diets. These data suggest that SSO and Quil A when present in the diet exerted cumulative effects that resulted in a decrease in the levels of dienoic eicosanoids with a reduction in IL-1beta and a concomitant elevation in the levels of IL-10 that were associated with a marked increase in survival in mice.

Topics: Animals; Dietary Supplements; Dinoprostone; Dioxoles; Eicosanoids; Fatty Acids; Female; Interleukins; Lignans; Liver; Membranes; Mice; Mice, Inbred BALB C; Quillaja Saponins; Saponins; Sesame Oil; Shock, Septic; Survival Analysis; Thromboxane B2

The furofuran lignans in sesame seed have an unusual oxygen insertion between their furan and aryl rings. In our continuing investigations on the isolation and characterization of the enzyme(s) involved, the diastereoselective syntheses of various substrate analogues for the oxygen insertion step were developed for future substrate specificity and inhibitor studies. This synthetic strategy also provided entry to so-called furofuranone epoxy-lignans, such as salicifoliol from Bupleurum sp., and acuminatolide from Helichrysum sp.

Topics: Dioxoles; Furans; Lignans; Magnoliopsida; Oxygen; Seeds; Sesame Oil; Stereoisomerism

Alkyl gallate, which is known as an antioxidant, intensively inhibited delta 5 and delta 6 desaturation in both rat liver microsomes and an arachidonic acid-producing fungus Mortierella alpina 1S-4. The rat liver microsomal delta 5 and delta 6 desaturases were inhibited by gallic acid esterified with alcohols with various numbers of carbons, suggesting that the necessary structure in an esterified alcohol for the inhibition is not so strict. Among the three hydroxy groups in gallic acid, the m-hydroxy group was shown to be the necessary structure. Kinetic analyses revealed that propyl gallate is a noncompetitive inhibitor of delta 5 desaturase (Ki = 2.6.10(-5)M) and delta 6 desaturase (Ki = 1.7.10(-4) M). These data indicate that alkyl gallate is a new type of desaturase inhibitor and different from known natural inhibitors, i.e., sesamin and curcumin.

Topics: Animals; Antioxidants; Delta-5 Fatty Acid Desaturase; Dioxoles; Enzyme Inhibitors; Fatty Acid Desaturases; Fatty Acids, Unsaturated; Fungi; Kinetics; Lignans; Male; Microsomes, Liver; Propyl Gallate; Rats; Rats, Wistar; Sesame Oil

Changes in the hepatic concentration of n-3 fatty acids, e.g., eicosapentaenoic acid and linolenic acid, were significantly reduced by their simultaneous administration with sesamin, whereas there was no such effect of sesamin for n-6 and n-9 fatty acids. However, there was no significant difference in lymphatic absorption between eicosapentaenoic acid (n-3) and arachidonic acid (n-6), irrespective of the presence of absence of sesamin.

Topics: Animals; Anticholesteremic Agents; Dioxoles; Eicosapentaenoic Acid; Fatty Acids; Lignans; Liver; Lymphatic System; Male; Rats; Rats, Wistar

Sesamin is known as a specific inhibitor of delta 5-desaturation, the conversion from dihomo-gamma-linolenic acid (20:3(n=6)) to arachidonic acid (20:4(n-6)). In the previous paper, we reported that sesamin inhibited delta 5-desaturation of n-6 fatty acids in rat hepatocytes but not that of n-3 fatty acids, from 20:4(n-3) to 20:5(n-3). Then, we studied the effects of sesamin on delta 5-desaturation of n-6 and n-3 fatty acids in vivo. Rats were fed two types of diets containing sesamin (0.5% w/w) for 4 weeks as follows: in experiment 1 (Exp. 1) gamma-linolenic acid-rich diet and in experiment 2 (Exp. 2) alpha-linolenic acid-rich diet. The fatty acid composition of liver lipids was compared to those of control groups without sesamin. In both Exps. 1 and 2, sesamin increased the liver weight and phospholipid contents in liver. In Exp. 2, sesamin increased n-6 fatty acids and decreased n-3 fatty acids even though the diet was rich in n-3 fatty acids. Sesamin enhanced the composition ratio of 20:3(n-6) in both Exps. 1 and 2. Decrease of delta 5-desaturation index of n-6 fatty acid, the ratio of 20:4(n-6)/20:3(n-6), by the administration of sesamin suggested that sesamin inhibited the delta 5-desaturation of n-6 fatty acids in the liver. On the contrary, the delta 5-desaturation index of n-3 fatty acids, the ratio of 20:5(n-3) to 18:3(n-3), was increased by sesamin administration in the liver of rats fed alpha-linolenic acid-rich diet (Exp. 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: alpha-Linolenic Acid; Animals; Diet; Dioxoles; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Lignans; Liver; Male; Rats; Rats, Wistar; Sesame Oil

We investigated the antihypertensive effect of sesamin, a lignan from sesame oil, using deoxycorticosterone acetate (DOCA)-salt hypertensive rats. The animals were unilaterally nephrectomized, and then separated into a sham-operated group (sham group) and a DOCA-salt-treated group. The latter was further separated into a normal diet group (control group) and a sesamin-containing diet group (sesamin group). The systolic blood pressure of control group progressively increased in comparison with that of sham group. This DOCA-salt-induced hypertension was markedly suppressed by feeding a sesamin-containing diet. Systolic blood pressure after 5 weeks was 130.6 +/- 1.9 mmHg in the sham group, 198.1 +/- 7.3 mmHg in the control group and 152.5 +/- 8.4 mmHg in the sesamin group, respectively. The treatment with DOCA and salt for 5 weeks significantly increased the weight of the left ventricle plus the septum. However, this increase was significantly suppressed in the sesamin group. When the degree of vascular hypertrophy of the aorta and superior mesenteric artery was histochemically evaluated, there were significant increases in wall thickness, wall area and the wall-to-lumen ratio in the control group, compared with the sham. Sesamin feeding ameliorated the development of DOCA-salt-induced vascular hypertrophy in both the aorta and mesenteric artery. These findings strongly suggest that sesamin is useful as a prophylactic treatment in the development of hypertension and cardiovascular hypertrophy.

Topics: Animals; Antihypertensive Agents; Aorta, Thoracic; Blood Pressure; Cardiomegaly; Desoxycorticosterone; Diet; Dioxoles; Hypertension; Hypertrophy; Lignans; Male; Nephrectomy; Rats; Rats, Sprague-Dawley

Six groups of rats were fed diets low, but adequate, in alpha-tocopherol but high in gamma-tocopherol. The six diets differed only in their contents (0, 0.25, 0.5, 1.0, 2.0, and 4.0 g/kg, respectively) of sesamin, a lignan from sesame oil. After four weeks of ad libitum feeding, the rats were sacrificed and the concentrations of alpha- and gamma-tocopherols were measured in the plasma, livers, and lungs. Sesamin-feeding increased gamma-tocopherol and gamma-/alpha-tocopherol ratios in the plasma (P < 0.05), liver (P < 0.001), and lungs (P < 0.001). The increase was non-significant for alpha-tocopherol. Thus, sesamin appears to spare gamma-tocopherol in rat plasma and tissues, and this effect persists in the presence of alpha-tocopherol, a known competitor to gamma-tocopherol. This suggests that the bioavailability of gamma-tocopherol is enhanced in phenol-containing diets as compared with purified diets.

Topics: Animals; Diet; Dioxoles; Lignans; Liver; Lung; Male; Rats; Rats, Sprague-Dawley; Regression Analysis; Sesame Oil; Vitamin E

Three series of experiments demonstrated that sesame seed and its lignans cause significant elevation of alpha-tocopherol content in rats. In Experiment 1, 20% sesame seed (with a negligible amount of alpha-tocopherol) supplementing 10 (low), 50 (normal), or 250 (high) mg/kg alpha-tocopherol diets (protein and fat concentrations in diets were adjusted to 200 and 110 g/kg, respectively) all caused a significant increase of alpha-tocopherol in the blood and tissue of rats. In Experiment 2, groups of rats were fed five different diets: a vitamin E-free control diet, a low alpha-tocopherol diet, and three low alpha-tocopherol diets supplemented with 5, 10, and 15% sesame seed. Changes in lipid peroxides in liver, red blood cell hemolysis, and pyruvate kinase activity, as indices of vitamin E deficiency, were examined. These indices were high in the low alpha-tocopherol diet, whereas supplementation with even 5% sesame seed suppressed these indices completely and caused a significant increase of alpha-tocopherol content in the plasma and liver. In Experiment 3, two diets containing sesame lignan (sesaminol or sesamin) and low alpha-tocopherol were tested. Results in both of the sesame lignan-fed groups were comparable to those observed in the sesame seed-fed groups as shown in Experiment 2. These experiments indicate that sesame seed lignans enhance vitamin E activity in rats fed a low alpha-tocopherol diet and cause a marked increase in alpha-tocopherol concentration in the blood and tissue of rats fed an alpha-tocopherol-containing diet with sesame seed or its lignans.

Topics: Animals; Antioxidants; Diet; Dioxoles; Furans; Kidney; Lignans; Liver; Male; Rats; Rats, Wistar; Vitamin E

Feeding sesamin and alpha-tocopherol in combination, both at the 0.5% dietary level, to Sprague-Dawley rats for 3 weeks resulted in a trend toward decreasing the proportion of 20:4n-6 and 22:5n-6 and increasing that of 18:2n-6 in phosphatidylcholine from various tissues, suggesting interference with the metabolism of linoleic acid. This dietary manipulation significantly reduced the production of leukotriene C4 in the lung, the splenic production of leukotriene B4, and reduction of the plasma histamine level. Simultaneous administration of sesamin and alpha-tocopherol significantly increased the production of IgA, IgG, and IgM by mesenteric lymph node lymphocytes, while the IgE level tended to be reduced. These effects were not necessarily apparent by feeding these compounds separately. Thus, sesamin and alpha-tocopherol in combination would be effective for regulating the eicosanoid production and modifying the immune function.

Topics: Animals; Anticholesteremic Agents; Body Weight; Dioxoles; Drug Interactions; Eicosanoids; Fatty Acids, Unsaturated; Histamine; Immunoglobulins; Lignans; Lipid Metabolism; Liver; Lymph Nodes; Lymphocytes; Male; Mesentery; Organ Size; Phosphatidylcholines; Rats; Rats, Sprague-Dawley; Spleen; Vitamin E

Sesamin is a specific inhibitor of delta 5 desaturation, the conversion from dihomo-gamma-linolenic acid (20:3, n-6) to arachidonic acid (AA, 20:4, n-6). Previously, we reported that sesamin inhibited delta 5 desaturation of n-6 fatty acids in rat hepatocytes but not that of n-3 fatty acids, from 20:4 (n-3) to eicosapentaenoic acid (EPA, 20:5, n-3). In this study, we investigated the interaction of sesamin and EPA on delta 5 desaturation of both series and the n-6/n-3 fatty acids ratio by measuring actural fatty acid contents in vivo. Rats were fed three types of dietary oils; 1) linoleic acid (LA, 18:2, n-6): linolenic acid (LLA, 18:3, n-3) = 3:1, n-6/n-3 ratio of 3:1 (LA group), 2) LA:LLA = 1:3, n-6/n-3 ratio of 1:3 (LLA group), 3) LA:LLA:EPA = 1:0.5:3, n-6/n-3 ratio of 1:3.5 (EPA group) with or without sesamin (0.5% w/w) for 4 weeks. In all groups, sesamin administration increased the content of dihomo-gamma-linolenic acid (20:3, n-6) in the liver and decreased the delta 5 desaturation index of n-6 fatty acid, the ratio of 20:4/20:3 (n-6). On the contrary, the delta 5 desaturation index of n-3 fatty acid, the ratio of 20:5 + 22:5 + 22:6/20:4 (n-3), was increased by the administration of sesamin. These results suggest that sesamin inhibits the delta 5 desaturation of n-6 fatty acid, but not that of n-3 fatty acid in rat livers. Sesamin administration decreased incorporation of EPA (n-3) and simultaneously increased the AA (n-6) content in the liver. The n-6/n-3 ratio in the liver was increased by administering sesamin under n-3 rich conditions, i.e., the LLA and EPA groups.

Topics: Animals; Anticholesteremic Agents; Body Weight; Brain; Dioxoles; Drug Interactions; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Lignans; Lipids; Liver; Male; Organ Size; Phosphatidylcholines; Rats; Rats, Wistar; Tissue Distribution

The effect of alpha-tocopherol on the hypocholesterolemic action of sesamin was examined in rats given a cholesterol-enriched diet. When different levels (0.05 and 0.2%) of sesamin were fed, the supplementation of 1% alpha-tocopherol significantly accentuated the hypocholesterolemic action of sesamin, particularly with the higher sesamin level, although alpha-tocopherol alone did not affect the concentration of serum cholesterol. The dose-dependent promoting effect of alpha-tocopherol on the hypocholesterolemic action of sesamin was confirmed by supplementing different levels (0.2 and 1%) of alpha-tocopherol to a fixed level of sesamin (0.2%). alpha-Tocopherol was still effective at the 0.2% level. The metabolism of sesamin in the liver S9 fraction appeared to be interfered with alpha-tocopherol in vitro, suggesting a possible role of alpha-tocopherol in maintenance of the availability of sesamin.

Topics: Animals; Anticholesteremic Agents; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Dioxoles; Drug Interactions; Lignans; Liver; Male; Organ Size; Rats; Rats, Wistar; Vitamin E; Weight Gain

We investigated the antihypertensive effect of sesamin, a lignan from sesame oil, using two-kidney, one-clip (2K,1C) renal hypertensive rats. After clipping the left renal artery, animals were assigned to either a normal diet group (control group) or a sesamin-containing (1% (w/w)) diet group (sesamin group). The sham-operated rats (sham group) were fed a normal diet and tap water. The systolic blood pressure of the control group increased progressively in comparison with the sham group. This 2K,1C-induced hypertension was markedly reduced by feeding the sesamin-containing diet. The systolic blood pressure after 4 weeks was 123.60 +/- 4.01 mmHg in the sham group, 187.43 +/- 5.69 mmHg in the control group and 145.57 +/- 6.78 mmHg in the sesamin group, respectively. There were significant increases in left ventricle plus septum weight-body weight ratio in the control group compared with the sham group. This rise was also significantly reduced in the sesamin group. When the thoracic aorta was histochemically evaluated, the wall thickness and wall-to-lumen ratio in the control group were significantly increased, compared with the sham group, indicating that vascular hypertrophy had occurred in the control group. The sesamin diet tended to ameliorate this vascular hypertrophy, although its effect was not statistically significant. These findings suggest that sesamin is useful as prophylactic treatment to combat the development of renal hypertension and cardiac hypertrophy.

Topics: Animals; Antihypertensive Agents; Cardiomegaly; Dioxoles; Hypertension, Renovascular; Lignans; Male; Rats; Rats, Sprague-Dawley; Sesame Oil

1. Effects of sesamin and episesamin (an epimer of sesamin) on lipid metabolism, in particular cholesterol metabolism, were examined in normocholesterolaemic and hypercholesterolaemic stroke-prone spontaneously hypertensive rats (SHRSP). 2. In normocholesterolaemic SHRSP fed a regular diet, both sesamin and episesamin significantly increased the concentration of serum total cholesterol, which was due to an increase of high density lipoprotein (HDL) subfraction rich in apoE (apoE-HDL). In addition, both substances effectively decreased serum very low density lipoprotein (VLDL). In the liver, only episesamin significantly decreased the activity of microsomal acyl-CoA:cholesterol acyltransferase. 3. In hypercholesterolaemic SHRSP fed a high-fat and high-cholesterol diet (HFC diet), only episesamin improved serum lipoprotein metabolism with an increase in apoA-I and a decrease in apoB. In the liver, both sesamin and episesamin significantly suppressed cholesterol accumulation. Interestingly, only episesamin significantly increased the activity of microsomal cholesterol 7alpha-hydroxylase. 4. These results indicate that sesamin may be effective in preventing cholesterol accumulation in the liver. In comparison with sesamin, episesamin may be effective in the regulation of cholesterol metabolism in the serum and liver.

Topics: Animals; Anticholesteremic Agents; Apolipoproteins; Blood Pressure; Cerebrovascular Disorders; Cholesterol; Dioxoles; Hypercholesterolemia; Lignans; Lipid Metabolism; Lipids; Male; Rats; Rats, Inbred SHR; Sterol O-Acyltransferase

The effects of a cholesterol-free diet, a cholesterol-free diet supplemented with sesamin, and a diet supplemented with sesamin on pancreatic carcinogenesis of N-nitrosobis(2-oxopropyl)amine (BOP) were investigated in 140 female Syrian golden hamsters. BOP (70 and 20 mg/kg body wt) was injected s.c. twice at an interval of 2 weeks at the beginning of the experiment. Starting 3 weeks thereafter, the animals were maintained on basal diet, cholesterol-free diet, basal diet plus sesamin, or cholesterol-free diet plus sesamin for a further 15 weeks. All surviving hamsters were killed at week 18, and the pancreatic tissues examined histologically. The incidences of pancreatic neoplastic and preneoplastic lesions in each group did not show any statistically significant variation. The cholesterol-free diet significantly decreased the cholesterol contents of the serum, pancreas and liver, and sesamin supplement significantly decreased the cholesterol contents of the serum and liver. Both the cholesterol-free diet and sesamin decreased the serum lipoperoxide levels. The results thus indicated that low cholesterol per se and sesamin exert no significant influence on BOP-initiated pancreatic carcinogenesis in hamsters, at least within the 4 month period after carcinogen treatment.

Topics: Animals; Carcinogens; Cholesterol; Cholestyramine Resin; Cricetinae; Dioxoles; Female; Lignans; Lipid Peroxides; Mesocricetus; Nitrosamines; Pancreas; Pancreatic Neoplasms

The effects of sesamin, a potent inhibitor of delta 5-desaturase in polyunsaturated fatty acid biosynthesis, on the fatty acid compositions of tissue lipids and liver functions were examined in rodents. When a mixture of sesamin and episesamin (51.1:48.2, w/w) was given to rats at a dietary level of 0.5% for 13 days, the proportions of dihomo-gamma-linolenic acid significantly increased not only in the liver but also in plasma and hemocytes, suggesting an interference with delta 5-desaturation by these lignans. The sesamin preparation at the dietary level of 1% improved changes in various blood parameters of the mouse, such as aspartate aminotransferase and alanine aminotransferase activities, and the concentrations of total cholesterol, triglyceride and total bilirubin, caused by continuous inhalation of ethanol. In addition, sesamin showed a significant protective effect against the accumulation of fat droplets and vacuolar degeneration in the mouse liver, as confirmed on histological examination. Sesamin, at the level of 100 mg/kg body weight, also tended to prevent liver lipid accumulation by carbon tetrachloride in mice. These results indicate that sesamin and a related lignan compound have an ability to improve liver function.

Topics: Administration, Inhalation; Alanine Transaminase; Animals; Aspartate Aminotransferases; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Dioxoles; Ethanol; Fatty Acid Desaturases; Fatty Acids; Lignans; Lipid Metabolism; Liver Diseases; Male; Mice; Microsomes, Liver; Rats; Rats, Wistar

Topics: Animals; Dioxoles; Hypercholesterolemia; Lignans; Lipase; Lipoprotein Lipase; Lipoproteins; Male; Rats; Rats, Inbred SHR

Effects of sesamin and curcumin on delta 5-desaturation and chain elongation of polyunsaturated fatty acid (PUFA) were studied in rat primary cultured hepatocytes. When sesamin was added to culture medium containing 20:4 (n-3), rat hepatocytes after 24 h of incubation produced 20:5 (n-3) from 20:4 (n-3), whereas when incubated with 20:3 (n-6), the metabolite by delta 5-desaturation did not accumulate, and consequently, the ratio of 20:3 (n-6)/20:4 (n-6) increased with the amount of sesamin added. Curcumin was more effective than sesamin in this respect. Both sesamin and curcumin interfered with chain elongation of PUFAs. An addition of 18:3 (n-6) or 18:4 (n-3) increased the cellular concentrations of 20:3 (n-6) or 20:4 (n-3), respectively, but the simultaneous addition of sesamin or curcumin inhibited the chain elongation of C18 acids (the fatty acids with 18 carbons) into corresponding C20 and C18 acids. Similarly, the elongation from C20 of n-3 and n-6 families to C22 was also inhibited with sesamin and curcumin. These results suggested that: 1) sesamin and curcumin inhibited delta 5-desaturation of n-6 fatty acid, but not n-3 fatty acid in rat hepatocytes; 2) curcumin was more effective than sesamin; 3) chain elongation was also inhibited by sesamin and curcumin.

Topics: Animals; Cells, Cultured; Curcumin; Dioxoles; Fatty Acid Desaturases; Fatty Acids, Unsaturated; Lignans; Liver; Male; Rats; Rats, Wistar

Vitamin E activity of sesame seed, which contains only gamma-tocopherol, a compound that has vitamin E activity equal to only 6-16% that of alpha-tocopherol, was examined in two experiments. In the first experiment, groups of rats were fed four diets: vitamin E-free control diet, alpha-tocopherol-containing diet, gamma-tocopherol-containing diet and sesame seed-containing diet. Changes in red blood cell hemolysis, plasma pyruvate kinase activity, and peroxides in plasma and liver, as indices of vitamin E activity, were examined. The sesame seed diet has high vitamin E activity, whereas this activity was low in the gamma-tocopherol diet. In plasma and liver, alpha-tocopherol was found in high concentration only in the alpha-tocopherol-fed group, and gamma-tocopherol was found in high concentration only in the sesame seed-fed group, with negligible amounts of gamma-tocopherol in liver of the gamma-tocopherol-fed group. In the second experiment, two diets containing sesame lignan (sesaminol or sesamin) and gamma-tocopherol were tested. Results in both of the sesame lignan-fed groups were comparable to those observed in the sesame seed-fed group in Experiment 1. These experiments indicate that gamma-tocopherol in sesame seed exerts vitamin E activity equal to that of alpha-tocopherol through a synergistic interaction with sesame seed lignans.

Topics: Animals; Diet; Dioxoles; Drug Synergism; Furans; Hemolysis; Lignans; Liver; Male; Peroxides; Pyruvate Kinase; Rats; Rats, Wistar; Vitamin E

The effects of sesamin, a lignan from sesame oil, on various aspects of cholesterol metabolism were examined in rats maintained on various dietary regimens. When given at a dietary level of 0.5% for 4 weeks, sesamin reduced the concentration of serum and liver cholesterol significantly irrespective of the presence or absence of cholesterol in the diet, except for one experiment in which the purified diet free of cholesterol was given. On feeding sesamin, there was a decrease in lymphatic absorption of cholesterol accompanying an increase in fecal excretion of neutral, but not acidic, steroids, particularly when the cholesterol-enriched diet was given. Sesamin inhibited micellar solubility of cholesterol, but not bile acids, whereas it neither bound taurocholate nor affected the absorption of fatty acids. Only a marginal proportion (ca. 0.15%) of sesamin administered intragastrically was recovered in the lymph. There was a significant reduction in the activity of liver microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase after feeding sesamin, although the activity of hepatic cholesterol 7 alpha-hydroxylase, drug metabolizing enzymes, and alcohol dehydrogenase remained uninfluenced. Although the weight and phospholipid concentration of the liver increased unequivocally on feeding sesamin, the histological examination by microscopy showed no abnormality, and the activity of serum GOT and GPT remained unchanged. Since sesamin lowered both serum and liver cholesterol levels by inhibiting absorption and synthesis of cholesterol simultaneously, it deserves further study as a possible hypocholesterolemic agent of natural origin.

Topics: Absorption; Alanine Transaminase; Animals; Anticholesteremic Agents; Aspartate Aminotransferases; Cholesterol; Dioxoles; Feces; Lignans; Lymph; Male; Microsomes, Liver; Organ Size; Rats; Rats, Inbred Strains; Sesame Oil; Taurocholic Acid

Incubation with sesame oil increases the mycelial dihomo-gamma-linolenic acid content of an arachidonic acid-producing fungus, Mortierella alpina, but decreases its arachidonic acid content [Shimizu, S., K. Akimoto, H. Kawashima, Y. Shinmen and H. Yamada (1989) J. Am. Oil Chem. Soc. 66, 237-241]. The factor causing these effects was isolated and identified to be (+)-sesamin. The results obtained in experiments with both a cell-free extract of the fungus and with rat liver microsomes demonstrated that (+)-sesamin specifically inhibits delta 5 desaturase at low concentrations, but does not inhibit delta 6, delta 9 and delta 12 desaturases. Kinetic analysis showed that (+)-sesamin is a noncompetitive inhibitor (Ki for rat liver delta 5 desaturase, 155 microM). (+)-Sesamolin, (+)-sesaminol and (+)-episesamin also inhibited only delta 5 desaturases of the fungus and liver. These results demonstrate that (+)-sesamin and related lignan compounds present in sesame seeds or its oil are specific inhibitors of delta 5 desaturase in polyunsaturated fatty acid biosynthesis in both microorganisms and animals.

Topics: Animals; Delta-5 Fatty Acid Desaturase; Dioxoles; Fatty Acid Desaturases; Fatty Acids, Unsaturated; In Vitro Techniques; Kinetics; Lignans; Male; Microsomes, Liver; Mucorales; Rats; Rats, Inbred Strains; Sesame Oil

Topics: Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Bridged-Ring Compounds; Chemical Phenomena; Chemistry; Dioxoles; Drugs, Chinese Herbal; Lignans; Oleanolic Acid; Triterpenes

Sesame oil has been reported to contain sesamolin, sesamin and sesamol as contact allergens. A female patient had cheilitis due to sesame oil in a lipstick. She reacted to sesamolin and sesamin, but not to sesamol. We carried out analysis of the sesame oil by high performance liquid chromatography. We detected sesamolin and sesamin but not sesamol in sesame oil.

Topics: Adult; Benzodioxoles; Cheilitis; Chromatography, High Pressure Liquid; Dermatitis, Contact; Dioxoles; Female; Humans; Lignans; Patch Tests; Phenols; Plant Oils; Sesame Oil

Topics: Dioxoles; Heterocyclic Compounds; Lignans