lignans and Body-Weight

Flaxseed (Linum usitatissimum) is an oil-based seed that contains high amounts of alpha-linolenic acid, linoleic acid, lignans, fiber and many other bioactive components which is suggested for a healthier life. Nowadays, flaxseed is known as a remarkable functional food with different health benefits for humans and protects against cardiovascular disease, diabetes, dyslipidemia, obesity and altogether metabolic syndrome.. To review the bioactive components of flaxseed and their potential health effects, PubMed and Scopus were searched from commencement to July 2019. Keywords including: "flaxseed", "Linum usitatissimum", "metabolic syndrome", "obesity", "inflammation", "insulin resistance", "diabetes", "hyperlipidemia" and "menopause" were searched in the databases with varying combinations.. Consumption of flaxseed in different forms has valuable effects and protects against cardiovascular disease, hypertension, diabetes, dyslipidemia, inflammation and some other complications. Flaxseed can serve as a promising candidate for the management of metabolic syndrome to control blood lipid levels, fasting blood sugar, insulin resistance, body weight, waist circumference, body mass and blood pressure.

Topics: alpha-Linolenic Acid; Blood Glucose; Body Weight; Cardiovascular Diseases; Diabetes Mellitus; Dietary Fiber; Drug Discovery; Dyslipidemias; Flax; Humans; Inflammation; Insulin Resistance; Lignans; Lipids; Metabolic Syndrome; Obesity; Plant Extracts; Seeds

This study aims at investigating the effect of an experimental period of intake of whole grain foods rich in lignans as part of an habitual diet on the plasma and urinary excretion of enterolignans, the biomarkers of lipid metabolism and the immunological and antioxidant status in a group of postmenopausal women with moderate serum cholesterol. A randomized double-blind crossover study was completed on 13 subjects in 12-weeks after protocol approval of an ethical committee. The subjects consumed whole grain foods high in lignans (30 g/d of breakfast cereals or biscuits, etc., 80 g/d of whole grain pasta) or refined grain foods for 4 weeks, separated by a 2-weeks wash-out period. A modest hypocholesterolemic effect (p < 0.05) of the whole grain diet was observed and the intake of whole grain products rich in lignans was also associated with an increase in urinary enterodiol excretion (p < 0.05).

Topics: Blood Pressure; Body Mass Index; Body Weight; Cholesterol; Cross-Over Studies; Diet; Double-Blind Method; Edible Grain; Female; Glutathione Peroxidase; Humans; Interleukin-1beta; Interleukin-6; Italy; Lignans; Middle Aged; Pilot Projects; Postmenopause; Superoxide Dismutase; Tumor Necrosis Factor-alpha

The omega-3 polyunsaturated fatty acid (n-3 PUFA) as well as lignan components of flaxseed (FLX) can have beneficial effects. In this 6-week-long, randomized, double-blinded, placebo-controlled study, we investigated the effects of FLX lignans on cardiovascular risk factors.. Thirty-seven subjects (13 men and 24 women, age: 54±7 years, body mass index [BMI]: 29.7±1 kg/m2) consumed nutrition bars with similar macronutrient contents. The fatty acid composition and the lignan contents of the bars differed significantly. Two FLX bars both contained 3.0 g of alpha linolenic acid (ALA: 18:3 n-3) but different amount of lignans (0.15 g vs. 0.41 g).. High-lignan FLX decreased total cholesterol (C) by 12% (p=0.044), LDL-C by 15% (p=0.022), and oxidized (Ox)-LDL by 25% (p=0.035). Regular FLX tended to increase Ox-LDL by 13% (p=0.051). The difference between the effects of high-lignan vs. regular lignan FLX on Ox-LDL was highly significant (p=0.004).. High-lignan FLX has the unique property of decreasing Ox-LDL, which is an independent risk factor for cardiovascular disease.

Topics: alpha-Linolenic Acid; Body Mass Index; Body Weight; Cardiovascular Diseases; Cholesterol, LDL; Double-Blind Method; Fatty Acid-Binding Proteins; Fatty Acids, Omega-3; Female; Flax; Humans; Lignans; Lipoproteins, LDL; Male; Middle Aged; Risk Factors; Soybean Oil; Triglycerides

The occurrence of menopause is associated with an increased risk of cardiovascular events, and this has partly been attributed to the decline in circulating levels of estrogen. A lignan complex rich in the plant lignan secoisolariciresinol diglucoside (SDG) was isolated from flaxseed. SDG is metabolized by the colonic microflora to the mammalian lignans enterodiol and enterolactone and is hypothesized to be cardioprotective due to their structural similarity to estrogen. The aim of this study was to investigate the effect of a lignan complex, providing 500 mg/d of SDG, on markers of endothelial function. Healthy postmenopausal women (n = 22) completed a randomized, double-blind, placebo-controlled, crossover study. Women consumed daily a low-fat muffin, with or without a lignan complex, for 6 wk, separated by a 6-wk washout period. Flow-mediated, endothelium-dependent vasodilatation (FMD) and nitroglycerine-mediated, endothelium-independent vasodilatation were measured at the end of each intervention period. The sum of Plasma nitrite and nitrate (NOx), endothelin-1 (ET-1), and asymmetric dimethylarginine (ADMA) were measured at the beginning and end of each intervention period. FMD was 3.6 +/- 0.9% (mean +/- SEM) after the lignan complex intervention period compared with 3.9 +/- 0.7% after the placebo period (P = 0.72). Plasma concentrations of NOx, ET-1, and ADMA were not affected. We conclude that daily consumption for 6 wk of a low-fat muffin enriched with a lignan complex had no effect on endothelial function in healthy postmenopausal women.

Topics: 4-Butyrolactone; Aged; Arginine; Blood Pressure; Body Weight; Cross-Over Studies; Diet; Double-Blind Method; Endothelin-1; Endothelium, Vascular; Female; Flax; Humans; Lignans; Middle Aged; Nitrates; Nitrites; Nitroglycerin; Patient Compliance; Placebos; Postmenopause; Vasodilation

Lignans and isoflavonoid phytoestrogens, produced from plant precursors by colonic bacteria, may protect against certain cancers. We examined the effects of flaxseed consumption on urinary lignans and isoflavonoids. Eighteen women consumed their usual omnivorous diets for three menstrual cycles and their usual diets supplemented with flaxseed powder (10 g/d) for three cycles in a randomized crossover design. Three-day urine samples from follicular and luteal phases were analyzed for lignans and isoflavonoids by isotope-dilution gas chromatography--mass spectrometry. Excretion of the lignans enterodiol and enterolactone increased with flaxseed from 1.09 +/- 1.08 and 3.16 +/- 1.47 to 19.48 +/- 1.10 and 27.79 +/- 1.50 mumol/d, respectively (P < 0.0002). Enterodiol and enterolactone excretion varied among subjects in response to flaxseed (3- to 285-fold increase). There were no differences in excretion of isoflavonoids (daidzein, genistein, equol, and O-desmethylangolensin) or the lignan matairesinol with flaxseed. Excretion was not altered by phase of menstrual cycle or duration of flaxseed consumption.

Topics: Administration, Oral; Adult; Body Weight; Diet; Dietary Fiber; Female; Gas Chromatography-Mass Spectrometry; Humans; Isoflavones; Lignans; Menstrual Cycle; Powders; Premenopause; Seeds

Type 2 diabetes mellitus (T2DM) is a metabolic risk factor associated with non-alcoholic liver disease (NAFLD). Schisandrin B (Sch B) is a promising agent for NAFLD. However, the actions of Sch B on diabetes-associated NAFLD and the underlying mechanisms are not characterized. This study aimed to assess whether Sch B has beneficial effects on T2DM-associated NAFLD. Sch B (50 mg/kg, gavage) was administrated to C57BL/KSJ db/db mice for 2 weeks. Body weight, liver weight, blood glucose, and insulin resistance were measured. Serum lipid level and liver function were detected using the biochemistry analyzer. Quantitative Real-Time PCR assay was used to evaluate mRNA levers of lipid metabolism genes. Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) staining was performed to measure apoptosis in the liver. Pathological analysis and immunohistochemistry assessment were used to analyze hepatic steatosis and inflammatory infiltration. Sch B supplementation significantly decrease body weight, related liver weight, blood glucose, and serum insulin, and improved insulin resistance in db/db mice. Sch B obviously corrected NAFLD phenotypes including lipid deposition, steatohepatitis, and high levels of hepatic enzymes and serum lipid. In addition, mRNA levels of Sterol response element-bind protein 1c (SREBP-1c), fatty acid synthetase (Fasn), and acetyl-CoA carboxylase (ACC) were markedly downregulated by Sch B treatment. TUNEL-positive cells were also decreased by Sch B. Furthermore, Sch B inhibited the Kupffer cells, IL-1β, and TNF-α infiltration to the liver. Sch B ameliorated insulin resistance and lipid accumulation under high glucose conditions, which was partly associated with its inhibition of apoptosis and anti-inflammatory actions.

Topics: Animals; Anti-Inflammatory Agents; Blood Glucose; Body Weight; Cyclooctanes; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Insulin Resistance; Lignans; Lipid Metabolism; Lipids; Liver; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Polycyclic Compounds; RNA, Messenger; Sterol Regulatory Element Binding Protein 1

Liver cancer is a critical clinical condition with augmented malignancy, rapid progression, and poor prognosis. Liver cancer often initiates as fibrosis, develops as cirrhosis, and results in cancer. For centuries, medicinal plants have been incorporated in various liver-associated complications, and recently, research has recognized that many bioactive compounds from medicinal plants may interact with targets related to liver disorders. Phyllanthin from the Phyllanthus species is one such compound extensively used by folklore practitioners for various health benefits. However, most practices continue to be unrecognized scientifically. Hence, in this work, we investigated the protective role of phyllanthin on diethylnitrosamine (DEN) induced liver carcinoma in Wistar Albino rats and the anti-tumor potential on human hepatocellular carcinoma (HCC) HepG2 cells. The DEN-challenged liver cancer in experimental rats caused increased liver weight, 8-OHD, hepatic tissue injury marker, lipid peroxidation, and tumor markers levels. Remarkably, phyllanthin counteracted the DEN effect by ameliorating all the liver function enzymes, oxidative DNA damage, and tumor-specific markers by enhanced anti-oxidant capacity and induced caspase-dependent apoptosis through the mTOR/ PI3K signaling pathway. MTT assay demonstrated that phyllanthin inhibited the HepG2 cell growth in a dose-dependent manner. Fascinatingly, phyllanthin did not demonstrate any substantial effect on the normal cell line, HL7702. In addition, HepG2 cells were found in the late apoptotic stage upon treatment with phyllanthin as depicted by acridine orange/ethidium bromide staining. Overall, this work offers scientific justification that phyllanthin can be claimed to be a safe candidate with potential chemotherapeutic activity against HCC.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antineoplastic Agents, Phytogenic; Antioxidants; Apoptosis; Biomarkers, Tumor; Body Weight; Cell Survival; Diethylnitrosamine; Disease Models, Animal; Hep G2 Cells; Humans; Lignans; Liver Neoplasms; Male; Oxidative Stress; Phosphatidylinositol 3-Kinase; Proto-Oncogene Proteins c-akt; Rats, Wistar; TOR Serine-Threonine Kinases

Diet has been the major focus of attention as a leading risk factor for non-communicable diseases, including mental health disorders. A large body of literature supports the hypothesis that there is a bidirectional association between sleep and diet quality, possibly via the modulation of neuro-inflammation, adult neurogenesis and synaptic and neuronal plasticity. In the present study, the association between dietary total, subclasses of and individual (poly)phenols and sleep quality was explored in a cohort of Italian adults.. The demographic and dietary characteristics of 1936 adults living in southern Italy were analyzed. Food frequency questionnaires (FFQs) were used to assess dietary intake. Data on the (poly)phenol content in foods were retrieved from the Phenol-Explorer database. The Pittsburg Sleep Quality Index was used to measure sleep quality. Multivariate logistic regression analyses were used to test the associations.. A significant inverse association between a higher dietary intake of lignans and inadequate sleep quality was found. Additionally, individuals with the highest quartile of hydroxycinnamic acid intake were less likely to have inadequate sleep quality. When individual compounds were taken into consideration, an association with sleep quality was observed for naringenin and apigenin among flavonoids, and for matairesinol among lignans. A secondary analysis was conducted, stratifying the population into normal weight and overweight/obese individuals. The findings in normal weight individuals showed a stronger association between certain classes of, subclasses of and individual compounds and sleep quality. Notably, nearly all individual compounds belonging to the lignan class were inversely associated with inadequate sleep quality. In the overweight/obese individuals, there were no associations between any dietary (poly)phenol class and sleep quality.. The results of this study suggest that a higher dietary intake of certain (poly)phenols may be associated with better sleep quality among adult individuals.

Topics: Adult; Body Weight; Cohort Studies; Coumaric Acids; Diet, Healthy; Dietary Supplements; Eating; Female; Flavonoids; Humans; Italy; Lignans; Male; Mental Health; Neurogenesis; Neuronal Plasticity; Nutritional Physiological Phenomena; Polyphenols; Sleep; Surveys and Questionnaires

Gomisin N (GN) is lignin derived from

Topics: Animals; Body Weight; Coconut Oil; Cyclooctanes; Diet, High-Fat; Disease Models, Animal; Drosophila melanogaster; Drosophila Proteins; Energy Metabolism; Gene Expression Regulation; HSP70 Heat-Shock Proteins; Humans; Lignans; Liver; Membrane Proteins; Obesity; Polycyclic Compounds; Schisandra

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

Sesame lignans, which are biologically active compounds present in sesame seeds and oil, are known to have neuroprotective effects in several models of brain dysfunction. However, the effects of sesame lignans on age-related brain dysfunction are not clear and were thus investigated in the present study using a senescence-accelerated mouse (SAMP10). Two-month-old male SAMP10 mice were administrated a basal diet with 0% or 0.05% sesame lignans for two months, or with 0%, 0.02%, or 0.05% sesame lignans for 10 months and subjected to step-through passive avoidance tasks and forced swim tests. Reactive carbonyl species (RCs) were evaluated as markers of oxidative stress using a recently developed comprehensive analytical method. Both learning time in passive avoidance tasks and immobile time in forced swim tests became longer with aging (

Topics: Aging; Animals; Body Weight; Brain; Cognitive Dysfunction; Humans; Lignans; Male; Mice; Mice, Inbred Strains; Organ Size; Sesamum; Survival Analysis

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease, and is associated with the development of metabolic syndrome. Postmenopausal women with estrogen deficiency are at a higher risk of progression to NAFLD. Estrogen has a protective effect against the progression of the disease. Currently, there are no safe and effective treatments for these liver diseases in postmenopausal women. Honokiol (Ho), a bioactive natural product derived from Magnolia spp, has anti-inflammatory, anti-angiogenic, and anti-oxidative properties. In our study, we investigated the beneficial effects of Ho on NAFLD in ovariectomized (OVX) mice. We divided the mice into four groups, as follows: SHAM, OVX, OVX+β-estradiol (0.4 mg/kg of bodyweight), and OVX+Ho (50 mg/kg of diet). Mice were fed diets with/without Ho for 12 weeks. The bodyweight, epidermal fat, and weights of liver tissue were lower in the OVX group than in the other groups. Ho improved hepatic steatosis and reduced proinflammatory cytokine levels. Moreover, Ho markedly downregulated plasma lipid levels. Our results indicate that Ho ameliorated OVX-induced fatty liver and inflammation, as well as associated lipid metabolism. These findings suggest that Ho may be hepatoprotective against NAFLD in postmenopausal women.

Topics: Adiposity; Animals; Biomarkers; Biphenyl Compounds; Body Weight; Cytokines; Disease Models, Animal; Fatty Liver; Gene Expression Profiling; Inflammation Mediators; Lignans; Lipid Metabolism; Liver; Mice; Non-alcoholic Fatty Liver Disease; Organ Size; Ovariectomy

7-Hydroxymatairesinol (7-HMR) is a plant lignan abundant in various concentrations in plant foods. The objective of this study was to test HMRLignan™, a purified form of 7-HMR, and the corresponding Picea abies extract (total extract P. abies; TEP) as dietary supplements on a background of a high-fat diet (HFD)-induced metabolic syndrome in mice and in the 3T3-L1 adipogenesis model. Mice, 3 weeks old, were fed a HFD for 60 d. Subgroups were treated with 3 mg/kg body weight 7-HMR (HMRLignan™) or 10 mg/kg body weight TEP by oral administration. 7-HMR and TEP limited the increase in body weight (-11 and -13 %) and fat mass (-11 and -18 %) in the HFD-fed mice. Epididymal adipocytes were 19 and -12 % smaller and the liver was less steatotic (-62 and -65 %). Serum lipids decreased in TEP-treated mice (-11 % cholesterol, -23 % LDL and -15 % TAG) and sugar metabolism was ameliorated by both lignan preparations, as shown by a more than 70 % decrease in insulin secretion and insulin resistance. The expression of several metabolic genes was modulated by the HFD with an effect that was reversed by lignan. In 3T3-L1 cells, the 7-HMR metabolites enterolactone (ENL) and enterodiol (END) showed a 40 % inhibition of cell differentiation accompanied by the inhibited expression of the adipogenic genes PPARγ, C/EBPα and aP2. Furthermore, END and ENL caused a 10 % reduction in TAG uptake in HEPA 1-6 hepatoma cells. In conclusion, 7-HMR and TEP reduce metabolic imbalances typical of the metabolic syndrome and obesity in male mice, whereas their metabolites inhibit adipogenesis and lipid uptake in vitro.

Topics: 3T3-L1 Cells; 4-Butyrolactone; Adipogenesis; Adipose Tissue; Animals; Anti-Obesity Agents; Blood Glucose; Body Weight; Diet, High-Fat; Dietary Supplements; Fatty Liver; Gene Expression; Insulin Resistance; Lignans; Lipid Metabolism; Lipids; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Obesity; Picea; Plant Extracts

Syringaresinol‑di‑O‑β‑D‑glucoside (SOG) is a phenolic compound extracted from Polygonatum sibiricum. The present study aimed to investigate the antidiabetic effect of SOG on streptozocin (STZ)‑induced diabetic mice and determine the potential underlying mechanisms. In the present study, fasting blood glucose and organ indexes of mice were analyzed. Body weight, water intake and food intake were also recorded. Furthermore, serum fasting insulin, pancreatic insulin and pancreatic interleukin‑6 levels of mice were determined using ELISA kits to investigate the effect of SOG on the levels of insulin. Levels of total cholesterol (TC), triglyceride (TG), high‑density lipoprotein cholesterol, low‑density lipoprotein cholesterol (LDL‑C), very low‑density lipoprotein cholesterol (VLDL‑C) and free fatty acid (FFA) in the serum of mice, and levels of TC, TG and total protein in the kidney, were also determined to investigate the effects of SOG on lipid and protein metabolism in mice. Furthermore, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) levels, as well as total antioxidant capacity (T‑AOC), in the kidneys of mice were determined to investigate the effect of SOG on oxidative stress. Western blotting was also performed to determine the expression of proteins associated with oxidative stress. The results demonstrated that SOG (25, 50 and 75 mg/kg) induced a significant antidiabetic effect in mice. Treatment with SOG promoted insulin secretion and decreased TC, TG, LDL‑C, VLDL‑C, FFA, MDA, SOD, CAT, AST, ALT and ALP levels in the kidneys of mice, as well as kidney TC and TG levels, but increased the levels of kidney total protein and the T‑AOC in kidneys. Furthermore, SOG treatment could significantly downregulate the expressions of nitrotyrosine and transforming growth factor‑β1 in diabetic mice. Therefore, the present study indicated that SOG may exert an antidiabetic effect on STZ‑induced diabetic mice and that the mechanism of SOG may be associated with its antioxidative activity.

Topics: Animals; Antioxidants; Biomarkers; Body Weight; Diabetes Mellitus, Experimental; Disease Models, Animal; Fasting; Glucosides; Hypoglycemic Agents; Insulin; Kidney; Lignans; Liver; Male; Mice; Plant Extracts; Polygonatum

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

Subcutaneous adipocytes in obese subjects have a lower sensitivity to catecholamine-induced lipolysis and a higher sensitivity to insulin anti-lipolytic effects compared to adipocytes in other adipose depots. Therefore, increasing lipolysis in subcutaneous adipocytes coupled with enhanced fatty acid oxidation may be an anti-obesity strategy. Schisandrin B (Sch B) is one of the most abundant active dibenzocyclooctadiene derivatives found in the fruit of Schisandra chinensis which is a commonly prescribed Chinese medicinal herb. We found that Sch B reduced glycerolipid contents in 3T3-L1 adipocytes and subcutaneous adipocytes dissected from DIO mice. Sch B also activated hormone sensitive lipase (HSL) and increased lipolysis in these adipocyte in a protein kinase A-dependent manner. Interestingly, Sch B increased fatty acid oxidation gene expressions in these adipocytes, implying an increase in fatty acid oxidation after treatment. In in vivo model, we found that Sch B increased HSL phosphorylation, reduced glycerolipid levels and increased fatty acid oxidation gene expressions in the subcutaneous adipocytes in the DIO mice. More importantly, Sch B significantly reduced the subcutaneous adipocyte sizes, subcutaneous adipose tissue mass and body weight of the mice. Our study provides scientific evidence to suggest a potential therapeutic function of Sch B or Schisandra chinensis seed containing Sch B in reducing obesity.

Topics: 3T3-L1 Cells; Adipocytes; Animals; Body Weight; Cyclooctanes; Disease Models, Animal; Enzyme Activation; Gene Expression Regulation; Glycolysis; Lignans; Lipase; Lipid Metabolism; Lipolysis; Mice; Molecular Structure; Obesity; Oxidation-Reduction; Polycyclic Compounds; Subcutaneous Fat

This study evaluated the protective effect of flaxseed oil (FO) and flaxseed lignan secoisolariciresinol diglucoside (SDG) against oxidative stress in rats with metabolic syndrome (MS). 48 rats were allocated into the following 6 groups: Groups 1 (control), 5 (FO), and 6 (SDG) received water and were treated daily orally with saline, FO, and SDG, respectively. Groups 2 (MS), 3 (MS+FO), and 4 (MS+SDG) received 30% fructose in drinking water for MS induction and were treated daily orally with saline, FO, and SDG, respectively. After 30 d, animals were sacrificed, and blood was collected for biochemical and oxidative analysis. Body weight was recorded weekly. Systolic blood pressure (SBP) was measured before and after treatment. Fructose could produce MS and oxidative stress. FO and SDG prevented changes in SBP, lipids, and glucose. FO and SDG prevented oxidative damage to lipids, and only FO prevented oxidative damage to proteins associated to MS. FO and SDG improved enzymatic antioxidants defenses and reduced glutathione levels, which was greater with SDG. Total polyphenol levels were enhanced in groups that received SDG. Thus, the results of this study demonstrated that treatment with a 30% fructose solution for 30 d is effective for MS induction and the oxidative stress is involved in the pathophysiology of MS induced by fructose-rich diets. Furthermore, we demonstrated that the antioxidant effects attributed to flaxseed are mainly due to its high lignan content especially that of SDG, suggesting that this compound can be used in isolation to prevent oxidative stress associated with MS.. We report that the antioxidant effects attributed to flaxseed are mainly due to its high lignan content, especially that of secoisolariciresinol diglucoside. This is significant because suggests that this compound can be used in isolation to prevent oxidative stress associated with MS. Furthermore, this study was the only one to perform a comparison of the abilities of 2 components of flaxseed to protect against oxidative stress in an MS model, which brings a great advance in the medicine's field, since it indicates another alternative for improve the health and the quality of life of patients with this disorder.

Topics: Animals; Antioxidants; Body Weight; Butylene Glycols; Flax; Fructose; Glucose; Glucosides; Humans; Lignans; Linseed Oil; Lipids; Male; Metabolic Syndrome; Oxidative Stress; Protective Agents; Quality of Life; Rats

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

To ascertain anti-fatigue constituents and mechanisms of Herpetospermum caudigerum.. The 80% ethanol extracts of Herpetospermum caudigerum were partitioned with chloroform, ethyl acetate and n-butanol, respectively. Male Kunming mice were divided into 13 groups with 16 mice in each group: a control group fed with water, 9 groups treated with 3 fractions of Herpetospermum caudigerum (chloroform fraction, ethyl acetate fraction and n-butanol fraction) at dose of 80, 160 and 320 mg/kg for the low-dose group, medium-dose group and high-dose group, 3 herpetrione (HPE) treated groups fed with HPE at dose of 15, 30, and 60 mg/kg for the low-dose group, medium-dose group and high-dose group. All animals were treated once per day for 30 days. Anti-fatigue activity was assessed through the forced swimming test and serum biochemical parameters including blood lactic acid (BLA), blood urea nitrogen (BUN), malondialdehyde (MDA), hepatic glycogen (HG), lactic dehydrogenase (LDH), superoxide dismutase (SOD) and glutathione peroxidase (GPx) determined following the recommended procedures provided by the commercial kits.. Compared with the control group, the lignans extract (ethyl acetate fraction) of Herpetospermum caudigerum and HPE could signifificantly prolonged the exhaustive swimming time (P<0.05 or P<0.01), and also increased the HG levels (P<0.05 or P<0.01) and the activities of antioxidant enzymes (SOD, GPx and LDH, P<0.05 or P<0.01); BLA and MDA levels were decreased considerably in lignans extract and HPE treated groups (P<0.05 or P<0.01). HPE also could significantly decrease the BUN contents compared with the control group (P<0.05). The chloroform and n-butanol fraction showed no effect on swimming time and biochemical parameters.. The lignans extract had antifatigue activities and HPE may be partly responsible for the anti-fatigue effects of Herpetospermum caudigerum. The possible mechanisms of anti-fatigue activity were related to the decrease of BUN and BLA, the increase of the HG storage and protecting corpuscular membrane by preventing lipid oxidation via modifying several enzyme activities.

Topics: Animals; Body Weight; Cucurbitaceae; Fatigue; Glycogen; Lignans; Liver; Male; Mice; Plant Extracts; Swimming; Time Factors

Results from animal studies have consistently suggested that lignans play a role in the regulation of in body weight, but evidence from human studies has been limited. We examined the associations between urinary excretion of enterolactone and enterodiol, the major intestinal microbial metabolites of dietary lignans, and 10-year prospective weight change using data from 2 well-characterized cohort studies of US women: the Nurses' Health Study (2000-2010) and Nurses' Health Study II (1997-2007). Urinary excretion levels of enterolactone and enterodiol were measured at baseline. Associations with prospective weight change were analyzed using a multivariable-adjusted linear mixed-effects model. We observed that women in the highest quartile of urinary excretion of total lignans had significantly lower baseline body mass indices (weight in kilograms divided by height in meters squared) (mean, 24.6, 95% confidence interval (CI): 23.9, 25.2) than did those in the lowest quartile (mean, 27.7, 95% CI: 27.0, 28.4; P for trend < 0.01). Compared with women in the lowest quartile of enterodiol excretion, those in the highest quartile gained 0.27 kg/year less weight (95% CI: 0.12, 0.41; P for trend < 0.01) during the 10-year follow-up. The association was borderline significant for enterolactone (for the fourth vs. first quartile, least square mean of weight change rate = -0.14 kg/year, 95% CI: -0.29, 0.00). Our data suggest that higher urinary excretion of lignan metabolites, especially enterodiol, is associated with modestly slower weight gain.

Topics: 4-Butyrolactone; Adult; Aged; Body Weight; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Incidence; Lignans; Middle Aged; Prospective Studies; United States; Urinalysis

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

Skeletal muscle atrophy, the most prominent phenotypic feature of cancer cachexia, is often observed in cancer patients undergoing chemotherapy. Magnolol (M) extracted from Magnolia officinalis exhibits several pharmacological effects including anti-inflammatory and anticancer activities. In this study, we investigated whether magnolol supplementation protects against the development of cachexia symptoms in bladder cancer-bearing mice undergoing chemotherapy. Combined treatment of magnolol with chemotherapeutic drugs, such as gemcitabine and cisplatin (TGCM) or gemcitabine (TGM), markedly attenuates the body weight loss and skeletal muscle atrophy compared with conventional chemotherapy (TGC). The antiatrophic effect of magnolol may be associated with inhibition of myostatin and activin A formation, as well as FoxO3 transcriptional activity resulting from Akt activation, thereby suppressing ubiquitin ligases MuRF-1 and MAFbx/atrogin-1 expression, as well as proteasomal enzyme activity. Notably, magnolol-induced insulin-like growth factor 1 (IGF-1) production and related protein synthesis may also contribute to its protective effects. The decreased food intake, and intestinal injury and dysfunction observed in the mice of TGC group were significantly improved in the TGCM and TGM groups. Moreover, the increased inflammatory responses evidenced by elevation of proinflammatory cytokine formation and NF-κB activation occurred in the atrophying muscle of TGC group were markedly inhibited in mice of combined treatment with magnolol. In summary, these findings support that magnolol is a promising chemopreventive supplement for preventing chemotherapy-induced skeletal muscle atrophy associated with cancer cachexia by suppressing muscle protein degradation, and inflammatory responses, as well as increasing IGF-1-mediated protein synthesis.

Topics: Animals; Biphenyl Compounds; Body Weight; Forkhead Box Protein O3; Forkhead Transcription Factors; Insulin-Like Growth Factor I; Interleukin-6; Lignans; Male; Mice; Mice, Nude; Muscular Atrophy; NF-kappa B; Proteasome Endopeptidase Complex; Tumor Necrosis Factor-alpha; Urinary Bladder Neoplasms

Tubulin is a well established target for anticancer drug development. Lignans and neolignans were synthesized as tubulin interacting agents. Neolignans 10 and 19 exhibited significant anticancer activity against MCF-7 and MDAMB-231 human breast cancer cell lines. Both the compounds effectively induced stabilization of microtubule at 4 and 20 μM concentrations respectively. Neolignan 10 induced G2/M phase arrest in MCF-7 cells. Docking experiments raveled that 10 and 19 occupied the same binding pocket of paclitaxel with some difference in active site amino acids and good bioavailability of both the compounds. In in vivo acute oral toxicity 10 was well tolerated up to 300 mg/kg dose in Swiss-albino mice.

Topics: Administration, Oral; Animals; Antineoplastic Agents; Binding Sites; Body Weight; Cell Line, Tumor; Coumaric Acids; Female; G2 Phase Cell Cycle Checkpoints; Half-Life; Humans; Lignans; M Phase Cell Cycle Checkpoints; Male; MCF-7 Cells; Mice; Molecular Docking Simulation; Protein Stability; Protein Structure, Tertiary; Tubulin

This study was designed to investigate the effect of w007B, a newly synthesized derivative of honokiol, on MCAO reperfusion, and its therapeutic time window and related mechanisms in rats. Neurological deficit scores, infarct size and brain water content were measured after 24 h reperfusion following 2 h ischemia. The results showed that w007B (10 and 50 μg/kg, IV immediately after reperfusion) markedly decreased neurological deficit scores, reduced infarct size and alleviated brain water content, and then 50 μg/kg w007B given within 3 h after reperfusion (5 h after ischemia) significantly attenuated ischemia-induced brain injury. Additionally, no sign of toxicity was observed when a single dose of 50mg/kg w007B (1000 times of the highest effective dose, IP) was administered. To explore the underlying mechanisms, the expression level of apoptosis, inflammation and autophagy-related markers in brain tissue were detected with kits or by western blot. It was observed that w007B rapidly and significantly reduced caspase-3 activity and NO production in the injured semi-brain, and also lowered the level of the p65 subunit of NF-κB in the nucleus. Besides, it also reduced the expression of Beclin-1 and LC3B-II, and increased the level of p62, the autophagy-related proteins in I/R-injured hemisphere. In conclusion, w007B exerts neuroprotective effect on cerebral ischemia-reperfusion injury with wider therapeutic time window and better safety; its mechanisms may be associated with its anti-inflammation, anti-apoptosis and anti-autophagy action. These results suggest that w007B shows strong potential as a clinical neuroprotective candidate for the treatment of ischemic stroke.

Topics: Animals; Apoptosis; Autophagy; Biphenyl Compounds; Body Weight; Cerebrovascular Circulation; Disease Models, Animal; Female; Inflammation; Lignans; Male; Mice; Mice, Inbred ICR; Neuroprotective Agents; NF-kappa B; Nitric Oxide; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Sex Factors; Time Factors

Obesity is caused by a combination of both genetic and environmental risks. Disruption in energy balance is one of these risk factors. In the present study, the preventive effect on high-fat diet- (HFD-) induced obesity and insulin resistance in mice by Magnolia bioactive constituent 4-O-methylhonokiol (MH) was compared with Magnolia officinalis extract BL153. C57BL/6J mice were fed by normal diet or by HFD with gavage-administered vehicle, BL153, low-dose MH, and high-dose MH simultaneously for 24 weeks, respectively. Either MH or BL153 slightly inhibited body-weight gain of mice by HFD feeding although the food intake had no obvious difference. Body fat mass and the epididymal white adipose tissue weight were also mildly decreased by MH or BL153. Moreover, MH significantly lowered HFD-induced plasma triglyceride, cholesterol levels and activity of alanine transaminase (ALT), liver weight and hepatic triglyceride level, and ameliorated hepatic steatosis. BL153 only significantly reduced ALT and liver triglyceride level. Concurrently, low-dose MH improved HFD-induced hyperinsulinemia and insulin resistance. Furthermore, the infiltration of mast cells in adipose tissue was decreased in MH or in BL153 treatment. These results suggested that Magnolia bioactive constituent MH might exhibit potential benefits for HFD-induced obesity by improvement of lipid metabolism and insulin resistance.

Topics: Adipose Tissue; Adiposity; Animals; Biphenyl Compounds; Blood Glucose; Body Weight; Cholesterol; Diet, High-Fat; Fatty Liver; Feeding Behavior; Glucose Tolerance Test; Inflammation; Insulin; Insulin Resistance; Lignans; Lipid Metabolism; Magnolia; Male; Mice, Inbred C57BL; Obesity; Protective Agents; Triglycerides

This study investigated the effect of honokiol (HON) and magnolol (MAG), phenolic compounds in Magnolia plants, on adiposity and adiposity-related metabolic disturbances in mice fed high-fat diet (HFD), and the potential underlying mechanisms focusing on the lipid metabolism and inflammatory response.. C57BL/6J mice were fed HFD (45 kcal% fat) with or without HON (0.02%, w/w) or MAG (0.02%, w/w) for 16 wk. Despite no changes in body weight, food intake, and hepatic fat accumulation, HON and MAG significantly lowered the weight of white adipose tissue (WAT) as well as adipocyte size and protected against insulin resistance induced by HFD. These effects were associated with increases in energy expenditure and adipose fatty acid oxidation and decreases in fatty acid synthase activity and expression of genes related to fatty acid synthesis, desaturation, and uptake, as well as adipocyte differentiation in WAT. Moreover, HON and MAG significantly lowered the expression of proinflammatory genes in WAT and elevated the plasma IL-10 level. Particularly, HON significantly decreased the plasma resistin level and increased the plasma adiponectin level compared to the control group.. HON and MAG have potential as novel agents for amelioration of adiposity and associated insulin resistance and inflammation.

Topics: Adipogenesis; Adiponectin; Adipose Tissue, White; Adiposity; Animals; Biphenyl Compounds; Blood Glucose; Body Weight; Chemokine CCL2; Cholesterol; Diet, High-Fat; Dietary Supplements; Energy Metabolism; Glucose Tolerance Test; Inflammation; Insulin Resistance; Interleukin-10; Interleukin-6; Lignans; Liver; Male; Mice; Mice, Inbred C57BL; Triglycerides; Tumor Necrosis Factor-alpha

Secoisolariciresinol diglycoside (SDG), a predominant lignan in flaxseed, has antioxidant activity as a dietary supplement. The purpose of the present study was to investigate the antidepressant-like effect and the possible mechanism of flaxseed SDG when the ovariectomized mice were exposed to the unpredictable chronic mild stress procedure. Chronic stress induced the increases in immobility time in mouse model of despair tests, but administration with SDG (80 and 160 mg/kg, p.o.) for 21 days inhibited these behavioral changes caused by stress in both forced swimming and tail suspension tests. These doses that affected the immobile response did not affect locomotor activity. Moreover, the changes in the serum corticosterone and adrenocorticotropic hormone (ACTH) levels were also measured to explore the SDG-associated regulation of hypothalamus-pituitary-adrenals (HPA) axis. The results indicated that the chronic stress-induced increases in the serum corticosterone and ACTH were reversed by treatment with high doses of SDG. Chronic treatment with SDG also affected the body weight of mice and IL-6, IL1β levels in the frontal cortex. In addition, chronic stress procedure induced a decrease in brain-derived neurotrophic factor (BDNF) expression in the frontal cortex of mice; while treatment with SDG reversed this reduction of BDNF. All these results provide compelling evidence that the behavioral effects of flaxseed SDG in the ovariectomized mice might be related to their modulating effects on the neuroendocrine-immune network and neurotrophin factor expression.

Topics: Adrenocorticotropic Hormone; Animals; Antidepressive Agents; Body Weight; Brain-Derived Neurotrophic Factor; Butylene Glycols; Corticosterone; Cytokines; Female; Flax; Glycosides; Lignans; Mice; Mice, Inbred ICR; Motor Activity; Ovariectomy; Stress, Psychological

The aim of the present study was to investigate the protective effects of gomisin A, a lignan compound isolated from Schisandra chinensis, against liver and kidney damage induced by CCl(4) exposure. We assessed alterations in organ weights, levels of serum biochemical indicators, and activation of the caspase-3 and MAPK signaling pathways and carried out histological analysis of liver and kidney tissue in rats pretreated with gomisin A for four days. In the gomisin A/CCl(4)-treated group, only the liver experienced a significant increase in weight, whereas the other organs did not undergo any changes. Five biochemical indicators in serum indicated that liver and kidney toxicity dramatically decreased upon gomisin A pretreatment, although the decrease in ratios varied. Upon histological analysis, the gomisin A/CCl(4)-treated group showed less hepatocellular necrosis, a poorly dilated central vein in the liver section, decreased diameter of the glomerulus, a lower number of capillaries, and a convoluted tubule in the kidney section. Furthermore, the formation of active caspase-3 was inhibited by gomisin A pretreatment in the gomisin A/CCl(4)-treated group, whereas the expression level of Bax protein was slightly increased. Western blot analysis revealed that there were differences between the liver and kidney in terms of activation of the MAPK signaling pathway. In the liver, gomisin A pretreatment increased phosphorylation of three members of the MAPK pathway when compared to that in the vehicle pretreatment group. However, in the kidney, only the phosphorylation level of p38 was elevated upon gomisin A pretreatment, whereas levels of the other two members were decreased. These results suggest that gomisin A induces marked protective effects against hepatic and renal injury induced by CCl(4) exposure through differential regulation of the MAPK signal transduction pathway.

Topics: Acute Kidney Injury; Analysis of Variance; Animals; Apoptosis; Body Weight; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Cyclooctanes; Dioxoles; Kidney; Lignans; Liver; MAP Kinase Signaling System; Organ Size; Phosphorylation; Protective Agents; Rats; Rats, Sprague-Dawley; Schisandra

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

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

We have previously shown that cinnamophilin ([8R, 8'S]-4, 4'-dihydroxy-3, 3'-dimethoxy-7-oxo-8, 8'-neolignan) exhibited potent antioxidant, radical-scavenging, and anti-inflammatory actions and reduced acute ischemic brain damage, even when it was given up to 6 hrs postinsult. Here, we characterized the long-lasting neuroprotection of cinnamophilin against gray and white matter damage and its beneficial effects on electrophysiological and functional outcomes in a model of stroke.. Prospective laboratory animal study.. Research laboratory in a university teaching hospital.. Adult male Sprague-Dawley rats (240-290 g).. Under controlled conditions of normoxia, normocarbia, and normothermia, spontaneously breathing, halothane-anesthetized (1.0-1.5%) rats were subjected to transient middle cerebral artery occlusion for 90 mins. Cinnamophilin (80 mg/kg) or vehicle was given intravenously at reperfusion onset.. Physiological parameters, including arterial blood gases and cortical blood perfusion, somatosensory-evoked potentials, and neurobehavioral outcomes, were serially examined. Animals were euthanized at 7 days or 21 days postinsult. Gray matter and white matter (axonal and myelin) damage were then evaluated by quantitative histopathology and immunohistochemistry against phosphorylated component-H neurofilaments and myelin basic protein, respectively. After the follow-up period of 7 and 21 days, our results showed that cinnamophilin significantly decreased gray matter damage by 31.6% and 34.9% (p < .05, respectively) without notable adverse effects. Additionally, cinnamophilin effectively reduced axonal and myelin damage by 46.3-68.6% (p < .05) and 25.2-28.1% (p < .05), respectively. Furthermore, cinnamophilin not only improved the ipsilateral field potentials (p < .05, respectively), but also reduced the severity of contralateral electrophysiological diaschisis (p < .05). Consequently, cinnamophilin improved sensorimotor outcomes up to 21 days postinsult (p < .05, respectively).. Administration with cinnamophilin provides long-lasting neuroprotection against gray and white matter damage and improves functional and electrophysiological outcomes after ischemic stroke. The results suggest a need for further studies to characterize the potential of cinnamophilin in the field of ischemic stroke.

Topics: Animals; Antioxidants; Behavior, Animal; Body Weight; Brain; Cerebral Cortex; Confidence Intervals; Disease Models, Animal; Electrophysiology; Evoked Potentials, Somatosensory; Guaiacol; Ischemic Attack, Transient; Lignans; Male; Nerve Fibers, Myelinated; Nerve Fibers, Unmyelinated; Neuroprotective Agents; Oxidative Stress; Random Allocation; Rats; Rats, Sprague-Dawley; Severity of Illness Index; Statistics, Nonparametric; Survival Rate

Eleutheroside E (EE), a principal component of Eleutherococcus senticosus, has been reported to have anti-inflammatory and protective effects in ischemia heart etc. However, whether it can mitigate behavioral alterations induced by sleep deprivation, has not yet been elucidated. Numerous studies have demonstrated that memory deficits induced by sleep deprivation in experimental animals can be used as a model of behavioral alterations. The present study investigated the effect of EE, on cognitive performances and biochemical parameters of sleep-deprived mice. Animals were repeatedly treated with saline, 10 or 50mg/kg EE and sleep-deprived for 72 h by the multiple platform method. Briefly, groups of 5-6 mice were placed in water tanks (45 × 34 × 17 cm), containing 12 platforms (3 cm in diameter) each, surrounded by water up to 1cm beneath the surface or kept in their home cage. After sleep deprivation, mice showed significant behavioral impairment as evident by reduced latency entering into a dark chamber, locomotion and correctly rate in Y maze, and increased monoamines in hippocampus. However, repeated treatment with EE restored these behavioral and biochemical alterations in mice. In conclusion, the beneficial effect of EE may provide an effective and powerful strategy to alleviate behavioral alterations induced by sleep deprivation.

Topics: Animals; Antioxidants; Avoidance Learning; Behavior, Animal; Body Weight; Disease Models, Animal; Dopamine; Glucosides; Glutathione; Hippocampus; Lignans; Locomotion; Male; Malondialdehyde; Maze Learning; Mice; Mice, Inbred ICR; Neurotransmitter Agents; Serotonin; Sleep Deprivation; Stress, Psychological; Time Factors

To study the acute and chronic toxicity of Tiangou Jiangya capsule.. Tiangou Jiangya capsule was intragastrically administered to mice twice a day. The appearance, behavior, mental status, respiratory changes of mice and the number of poisoned and dead mice in each group were noted daily for 14 consecutive days. The amount of weight and feed of survived mice were recorded every day. The mice were divided into four groups: the treatment groups (minimum, middle, maximum dose of Tiangou Jiangya capsule) and the control group. After continuously orally administrated for 6 months, the rats' behavior, weight gain, food consumption, indications for hematology, blood biochemistry, urine analysis, electrocardiogram, systematic autopsy and histopathology were observed. The above physiological indexes were inspected again 1 month after cease of administration.. The oral acute toxicity study of Tiangou Jiangya capsule in mice revealed that the maximum dose is 534.86 g x kg(-1), which was 534.86 times the recommended human maximum dose in clinical practice. Compared with normal control group, no significant differences were observed in rats' behaviors, food-intake, electrocardiogram and relative examination indexes among the treatment groups. There was no difference of hematology, biochemistry test, urine and histopathology.. The minimum dosage of Tiangou Jiangya capsule is relatively safe. It caused weight loss by administrated with the middle and maximum dose for 6 months, which should be paid attention in clinical studies.

Topics: Animals; Antihypertensive Agents; Behavior, Animal; Benzyl Alcohols; Body Weight; Drugs, Chinese Herbal; Eating; Electrocardiography; Female; Flavonoids; Furans; Glucosides; Lignans; Male; Mice; Mice, Inbred ICR; Rats; Rats, Wistar

The present study involved a comparative analysis of the effects of purified flaxseed lignans, secoisolariciresinol diglucoside (SDG) and its aglycone metabolite (SECO), in hyperlipidaemic rats. For hypercholesterolaemia, female Wistars (six rats per group) were fed a standard or 1 % cholesterol diet and orally administered 0, 3 or 6 mg SDG/kg or 0, 1.6 or 3.2 mg SECO/kg body weight once daily for 4 weeks. Hypertriacylglycerolaemia was induced in male Sprague-Dawley rats (ten rats per group) by supplementing tap water with 10 % fructose. These rats were orally administered 0, 3 or 6 mg SDG/kg body weight once daily for 2 weeks. Fasting blood samples (12 h) were collected predose and at the end of the dosing period for serum lipid analyses. Rats were killed and livers rapidly excised and sectioned for lipid, mRNA and histological analyses. Chronic administration of equimolar amounts of SDG and SECO caused similar dose-dependent reductions in rate of body-weight gain and in serum total and LDL-cholesterol levels and hepatic lipid accumulation. SDG and SECO failed to alter hepatic gene expression of commonly reported regulatory targets of lipid homeostasis. SDG had no effect on serum TAG, NEFA, phospholipids and rate of weight gain in 10 % fructose-supplemented rats. In conclusion, our data suggest that the lignan component of flaxseed contributes to the hypocholesterolaemic effects of flaxseed consumption observed in humans. Future studies plan to identify the biochemical mechanism(s) through which flaxseed lignans exert their beneficial effects and the lignan form(s) responsible.

Topics: Animals; Base Sequence; Body Weight; Butylene Glycols; Dose-Response Relationship, Drug; Female; Flax; Fructose; Gene Expression; Glucosides; Hyperlipidemias; Lignans; Lipids; Liver; Male; Models, Animal; Molecular Sequence Data; Random Allocation; Rats; Rats, Sprague-Dawley; Rats, Wistar

Flax lignan complex suppresses the development of hypercholesterolemic atherosclerosis. However, it is not known whether flax lignan complex would slow down the progression of hypercholesterolemic atherosclerosis. This study was carried out to determine whether flax lignan complex slows down the progression of already developed atherosclerosis, and whether this effect is associated with reductions in serum lipids and oxidative stress. The studies were conducted in 4 groups of rabbits: group I, regular diet (2 months); group II, 0.25% cholesterol diet (2 months); group III, 0.25% cholesterol diet (4 months); group IV, 0.25% cholesterol diet (2 months) followed by 0.25% cholesterol diet plus flax lignan complex (2 months). Serum lipids and oxidative stress parameters (malondialdehyde, antioxidant reserve, white blood cell chemiluminescence) were measured before and at monthly intervals thereafter on their respective diets. Aortas were removed at the end of the protocol for assessment of atherosclerosis and oxidative stress. Atherosclerosis in group II was associated with hyperlipidemia and increased oxidative stress. Significant areas of the aortic intimal surfaces from group II (37.76% + 7.96%), group III (76.6% + 9.04%), and group IV (52.95% + 10.29%) were covered with atherosclerotic plaques. Group IV rabbits had 40% more atherosclerotic lesions than group II but 31% fewer lesions than group III. The flax lignan complex-induced reduction in the progression of atherosclerosis was associated with reductions in oxidative stress. In conclusion, flax lignan complex was effective in slowing down the progression of atherosclerosis by 31%, and this effect was associated with a reduction in oxidative stress.

Topics: Animals; Anticholesteremic Agents; Antioxidants; Aorta; Atherosclerosis; Body Weight; Disease Models, Animal; Disease Progression; Flax; Hypercholesterolemia; Leukocytes; Lignans; Lipids; Malondialdehyde; Oxidative Stress; Rabbits; Time Factors

Cinnamophilin (CINN, (8R, 8'S)-4, 4'-dihydroxy-3, 3'-dimethoxy-7-oxo-8, 8'-neolignan) protects against ischemic stroke in mice. While some anti-oxidative effects of CINN have been characterized, its therapeutic window and molecular basis for neuroprotection remain unclear. We evaluated antioxidant and anti-inflammatory properties and therapeutic window of CINN against brain ischemia using a panel of in vitro and in vivo assays. Data from lipid peroxidation and radical scavenging assays showed that CINN was a robust antioxidant and radical scavenger. CINN effectively inhibited the production of tumor necrosis factor alpha (TNF-alpha), nitrite/nitrate, interleukin-6 (IL-6) in lipopolysaccharide (LPS)-stimulated RAW 264.7 and BV2 cells (P<0.05, respectively). Relative to controls, CINN, administrated at 80 mg/kg, 2, 4, or 6 h postinsult, but not 12 h, significantly reduced brain infarction by 34-43% (P<0.05) and improved neurobehavioral outcome (P<0.05) following transient focal cerebral ischemia in rats. CINN (10-30 microM) also significantly reduced oxygen-glucose deprivation-induced neuronal damage (P<0.05) in rat organotypic hippocampal slices, even when it was administrated 2, 4, or 6 h postinsult. Together, CINN protects against ischemic brain damage with a therapeutic window up to 6 h in vivo and in vitro, which may, at least in part, be attributed by its direct antioxidant and anti-inflammatory effects.

Topics: Analysis of Variance; Animals; Animals, Newborn; Antioxidants; Benzothiazoles; Body Weight; Cell Line, Transformed; Disease Models, Animal; Dose-Response Relationship, Drug; Glucose; Guaiacol; Hippocampus; Hypoxia; Interleukin-6; Ischemic Attack, Transient; Lignans; Lipid Peroxidation; Microglia; Nitrates; Nitrites; Organ Culture Techniques; Peroxidase; Phenethylamines; Polysaccharides; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Sulfonic Acids; Time Factors; Tumor Necrosis Factor-alpha

The inhibitory effect of (-)-, (+)-matairesinol and (-)-, (+)-secoisolariciresinol on the discoloration of dark muscle (chiai in Japanese) of two-year-old yellowtail (hamachi in Japanese) was evaluated by measuring the X and a(*) values. (-)-Matairesinol was most effective for retaining the red color of dark muscle in this experiment.

Topics: Animals; Antioxidants; Body Weight; Butylene Glycols; Color; Female; Food Preservation; Furans; Lignans; Maillard Reaction; Meat; Mice; Mice, Inbred BALB C; Muscles; Perciformes; Solutions

Phytochemicals endowed with hormonal, antihormonal, or toxic activity are potential agents for insect control. Thus, we became interested in testing Brazilian plant metabolites on Chrysomya megacephala (F.) (Diptera: Calliphoridae), a public health menace that is one of the most prevalent flies in Brazilian urban areas. We tested the lignan yangambin, from the leaves of Ocotea duckei Vattimo (Lauraceae). Topical treatment of eggs and first instars with yangambin as well as feeding larvae a yangambin-treated diet resulted in inhibition of postembryonic development, morphological alteration, and oviposition reduction.

Topics: Administration, Oral; Animals; Body Weight; Diptera; Female; Furans; Insect Control; Larva; Lignans; Male; Ocotea; Ovum; Plant Extracts; Sex Ratio; Time Factors

The neuroprotective effect of 9-hydroxypinoresinol was examined in mice challenged with kainic acid (KA), a potent central nervous system excitotoxin. For this purpose, mice were administered intraperitoneally with 9-hydroxypinoresinol before KA injection. A remarkable neuroprotective effect was observed with a single dose of 9-hydroxypinoresinol (30 mg kg(-1)) 24 h before KA challenge. Furthermore, 9-hydroxypinoresinol (20 mg kg(-1)) administered for 3 days before KA challenge reduced the mortality (60%) induced by KA to zero, and alleviated behavioural signs of KA neurotoxicity. Additionally, pretreatment with 9-hydroxypinoresinol (20 mg kg(-1)) prevented the decrease in the levels of total glutathione (GSH) and thiobarbituric acid reactive substances (P < 0.05). GSH peroxidase activity in brain tissue was restored to control levels, although GSH reductase activity and GSH S-transferase activity were not affected. Such a protective action was also observed even with a lower dose (10 mg kg(-1)) of 9-hydroxypinoresinol administered for 3 days, albeit to a lesser extent. From the results, it is proposed that 9-hydroxypinoresinol exerts a potent neuroprotective effect mainly by preventing oxidative stress in brain tissue of mice challenged with KA.

Topics: Animals; Antioxidants; Behavior, Animal; Body Weight; Brain; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Glutathione Transferase; Kainic Acid; Lignans; Lipid Peroxidation; Male; Mice; Mice, Inbred ICR; Neurotoxins; Organ Size; Oxidative Stress; Thiobarbituric Acid Reactive Substances

This study determined the effect of the mammalian lignans enterolactone (ENL) and enterodiol (END) alone and in combination with the isoflavone genistein (GEN) on the growth of MCF-7 tumors in ovariectomized nude mice. Ovariectomized athymic nude mice with established MCF-7 tumors were fed a basal diet (AIN-93G) and divided into 5 groups that received daily subcutaneous injections (10 mg/kg body weight (BW)) of ENL, END, GEN, a mixture of these compounds (MIX), or vehicle as a negative control for 22 weeks. A positive control group was implanted with an estradiol pellet in order to establish an estrogenic tumor growth response. In the ENL- and END-treated mice, palpable tumors regressed significantly by 91 and 83%, respectively, resulting in final tumors that were similar to the negative control tumors. However, tumor cell apoptosis was significantly enhanced by the lignans. In the GEN-treated mice, tumors initially regressed significantly by 64% but regression ceased following prolonged treatment, resulting in final tumors that were significantly larger compared to negative control, ENL-, and END-treated mice, in part by increasing tumor cell proliferation. The MIX treatment significantly regressed palpable tumors by 87% similar to negative control group, with no effects on tumor cell apoptosis or proliferation. The isoflavone GEN alone promoted the growth of established MCF-7 human breast cancer xenografts after prolonged treatment while the mammalian lignans ENL and END did not. When these phytoestrogens were given in combination, no tumor growth-promoting effects were observed. (c) 2005 Wiley-Liss, Inc.

Topics: 4-Butyrolactone; Animals; Apoptosis; Body Weight; Cell Line, Tumor; Cell Proliferation; Drug Therapy, Combination; Feeding Behavior; Genistein; Humans; Lignans; Mice; Mice, Nude; Neoplasms; Ovariectomy; Xenograft Model Antitumor Assays

Isotaxiresinol, the main lignan isolated from the water extract of wood of Taxus yunnanensis, was investigated for its effect on bone loss, on serum biochemical markers for bone remodeling and on uterine tissue, using ovariectomized (OVX) rats as the model of postmenopausal osteoporosis. After oral administration of isotaxiresinol (50 and 100mg/kg/d) for 6 weeks, bone mineral content (BMC) and bone mineral density (BMD) in total and cortical bones were increased as compared to those of OVX control rats, and decreases of three bone strength indexes induced by OVX surgery were prevented. Serum biochemical markers for bone remodeling revealed that isotaxiresinol slightly increased bone formation and significantly inhibited bone resorption without side effect on uterine tissue. These results suggest that isotaxiresinol may be useful for treatment of postmenopausal osteoporosis, especially for prevention of bone fracture induced by estrogen deficiency.

Topics: Animals; Body Weight; Bone Density; Dose-Response Relationship, Drug; Female; Lignans; Molecular Structure; Osteoporosis; Ovariectomy; Rats; Rats, Wistar; Taxus

Plant lignan 7-hydroxymatairesinol (7-HMR) is a novel precursor of the mammalian lignan enterolactone. A 13 week toxicity study at dietary levels of 0, 0.25, 1, and 4% (w/w) of potassium acetate complex of 7-HMR (HMRlignan) was conducted in the Wistar rat. These dietary levels resulted in an average daily intake of 160, 640, and 2600 mg HMRlignan/kg body weight/day, respectively. A considerable systemic exposure of HMRlignan was verified by dose-related increases in plasma total (conjugated and unconjugated) concentration of 7-HMR and metabolites enterolactone, 7-hydroxyenterolactone, and matairesinol. Enterolactone appeared to be the major metabolite. Most (>96%) of the circulating 7-HMR and enterolactone was in conjugated form as measured from the low-dose rat plasma samples. HMRlignan exposure did not significantly affect clinical signs, ophthalmoscopy or neurobehavioural observations, and motor activity. Transient reductions in food intake and body weight gain in the mid-and high-dose group were ascribed to decreased palatability of the test feed. Only in males of the high-dose group the body weights remained slightly reduced throughout the study. In the high-dose group the number of thrombocytes (females), and total white blood cell count (males) were increased. Plasma triglycerides were dose-dependently depressed in males of all test groups and in females of the mid- and high-dose group, while plasma total cholesterol, and phospholipids were decreased in high-dose males. These changes, which have also been reported for other (flaxseed) lignans, were not considered to represent adverse effects. The relative weight of the kidneys was increased in males of the high-dose group. The weight of the full and empty caecum showed dose-related increases in males of all treatment groups and in females of the high-dose group. Absolute ovary weights were decreased in all treatment groups while decreases in relative ovary weights were confined to the mid- and high-dose group. In addition, a marginal lengthening of the estrus cycle was noted in high-dose females. Apart from prevention of hyaline droplet nephropathy in all high-dose male rats, there were no treatment-related histopathological alterations. It was concluded that HMRlignan showed weak antiestrogen-like activity which may be mediated through enterolactone metabolite. Based on declined ovary weight, the no observed adverse effect level of HMRlignan was set at 0.25% in feed corresponding to 160 mg/kg body

Topics: 4-Butyrolactone; Animals; Body Weight; Diet; Female; Lignans; Male; Motor Activity; No-Observed-Adverse-Effect Level; Organ Size; Potassium Acetate; Rats; Rats, Wistar

A primary methanol extract (F-ME), secondary butanol-soluble fraction (F-BU), and lignans were prepared from forsythia fruit (Forsythia viridissima L.) and added to 0.5% (w/w) cholesterol diets for male Sprague-Dawley rats weighing 121 +/- 12 g. There were six experimental groups: a control group, 0.2%, 0.4% F-ME supplemented groups, 0.1%, 0.02% F-BU groups and 0.02% lignan group. After 3 weeks of feeding, body weight gains, serum GOT and GPT levels were not different among the groups. HDL-/total cholesterol ratios increased in the 0.2% F-BU and lignan groups compared with the control groups. Liver triglyceride level lowered in most of forsythia groups. Fecal cholesterol excretions increased in the lignan group. Arctiin isolated from the forsythia fruit reduced cholesterol and triglyceride contents in cultured HepG2 cells at 0.01-0.1 microM. These results indicated that the forsythia lignan, arctiin is effective on improving blood lipid status without a significant hepatotoxicity and is to be utilized for the functional foods for lipid-lowering action.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Body Weight; Cell Line, Tumor; Cholesterol, Dietary; Dietary Supplements; Forsythia; Furans; Glucosides; Humans; Lignans; Lipid Metabolism; Lipids; Male; Plant Extracts; Rats; Rats, Sprague-Dawley; Seeds

Previous studies have shown that feeding flaxseed (FS) or its lignan secoisolariciresinol diglucoside (SDG) to rat dams during lactation enhances the differentiation of rat mammary gland in the female offspring. This study determined whether exposure to a diet with 10% FS or SDG (equivalent to the amount in 10% FS) during suckling could protect against 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced rat mammary tumorigenesis later in life. Dams were fed the AIN-93G basal diet (BD) throughout pregnancy. After delivery, dams were randomized to continue on BD or were fed BD supplemented with 10% FS or SDG during lactation. Three-day urine of dams was analyzed for mammalian lignans. After weaning, all offspring were fed BD. At postnatal Days 49 to 51, during proestrus phase, offspring were gavaged with 5 mg of DMBA. At Week 21 post-DMBA administration, compared with the BD group, the FS and SDG groups had significantly lower (P < 0.05) tumor incidence (31.3% and 42.0% lower, respectively), total tumor load (50.8% and 62.5% lower, respectively), mean tumor size (43.9% and 67.7% lower, respectively), and tumor number (46.9% and 44.8% lower, respectively) per rat. There was a significant decreasing trend (P < 0.05) in final tumor weights in rats fed FS or SDG. The high urinary lignan excretion in dams fed with FS or SDG corresponded with the reduced tumor development. The FS and SDG groups did not differ significantly in tumor indices, indicating that the effect of FS is primarily due to its SDG. There were no significant changes in selective reproductive indices measured among dams and offspring. In conclusion, exposure to FS or SDG during suckling suppressed DMBA-induced rat mammary tumorigenesis, suggesting that exposure to lignans at this early stage of mammary gland development reduces susceptibility to mammary carcinogenesis later in life without adverse effects on selective reproductive indices in dams or offspring.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Animals, Suckling; Body Weight; Butylene Glycols; Carcinogens; Diet; Disease Models, Animal; Female; Flax; Glucosides; Lactation; Lignans; Mammary Neoplasms, Experimental; Rats; Rats, Sprague-Dawley; Reproduction

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

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

Based on the reported health benefits of flaxseed, many Canadians are choosing to consume flaxseed or flaxseed-containing foods. However, the safety of exposure to flaxseed during early life such as the suckling period has not been studied, despite the fact that components in flaxseed with potential hormone-like effects can be transferred to nursing offspring via mother's milk. Previous investigations demonstrated that maternal feeding of a 10% flaxseed diet during pregnancy and lactation resulted in estrogenic effects on reproductive indices among male and female offspring. These effects were attributed to the potential estrogenic activity of enterodiol and enterolactone, the two major mammalian lignans that are converted from secoisolariciresinol diglycoside (SDG) in flaxseed by colonic bacteria; however, the effect of exposure to purified SDG at the level of a 10% flaxseed diet was not studied. The objective of this study was to determine whether maternal feeding of flaxseed during lactation altered reproductive indices in male and female offspring. Rat dams were fed basal diet (BD) or BD containing either 100% flaxseed (10F) or the equivalent quantity of SDG present in the 10% (10S) flaxseed diet from the start of lactation until pups were 21 d old. At the end of lactation (postnatal day IPND] 21), suckling pups either continued on the mother's diet or were switched to BD until adolescence (PND 50) or young adulthood (PND 132) to determine if continuous exposure to flaxseed or SDG altered reproductive indices. The reproductive indices that were measured included anogenital distance from birth through PND 21, age and body weight at puberty onset (females only), estrous cycle length, reproductive organ weights at PND 50 and 132, and histological analysis of reproductive organs (uterus, ovaries, prostate) at PND 132. There were no significant effects of exposing male or female offspring to flaxseed or SDG during suckling only or during suckling through the postsuckling period on any of the reproductive indices measured. These findings are in contrast to the estrogenic effects observed in male and female offspring exposed to flaxseed during fetal life through suckling and suggest that fetal life is a more hormone-sensitive period of development. Although maternal feeding of flaxseed during lactation appears to be safe with respect to reproductive indices among offspring, future investigation is required to elucidate whether there are any long-term implica

Topics: Age Factors; Analysis of Variance; Animals; Animals, Suckling; Body Weight; Disease Models, Animal; Drug Evaluation, Preclinical; Female; Flax; Infertility; Lactation; Lignans; Male; Maternal Exposure; Random Allocation; Rats; Rats, Sprague-Dawley; Reproduction; Time 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

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

Flaxseed and its lignan secoisolariciresinol diglycoside (SDG) inhibit mammary tumor development in rats. Increased plasma insulin-like growth factor I (IGF-I) concentrations are associated with increased breast cancer risk. Therefore, the effect of flaxseed (5%) or SDG (1.5 mg/day) supplementation on plasma IGF-I levels was examined in rats treated with or without N-methyl-N-nitrosourea (MNU). In MNU-free rats, flaxseed and SDG reduced plasma IGF-I levels, which were inversely related to urinary lignan excretion. Only flaxseed significantly reduced plasma IGF-I concentrations in MNU-treated rats. The anticancer effect of flaxseed and SDG may be related, in part, to reductions in plasma IGF-I.

Topics: Animals; Anticarcinogenic Agents; Body Weight; Butylene Glycols; Carcinogens; Dietary Supplements; Eating; Female; Flax; Glucosides; Insulin-Like Growth Factor I; Lignans; Mammary Glands, Animal; Methylnitrosourea; Organ Size; Rats; Rats, Sprague-Dawley

We studied the effects of a lignan, hydroxymatairesinol (HMR), and rye bran on intestinal tumor development in adenomatous polyposis colimultiple intestinal neoplasia (Apc)(Min) mice. HMR showed a strong chemopreventive effect in this animal model. The mean number of adenomas in the small intestine was significantly lower (26. 6+/-11.0, P<0.05) in mice fed the inulin and HMR when compared with the inulin and inulin/rye bran fed mice (39.6+/-8.9 and 36.0+/-7.4, respectively). HMR resulted in normalization of beta-catenin levels in adenoma tissue, indicating that HMR mediates its chemopreventive effect through the Apc-beta-catenin pathway. In the cytosolic fraction, beta-catenin level in adenoma tissue was significantly elevated (P=0.008-0.013) in all the diet groups as compared with that of the surrounding mucosa. In the nuclear fraction, beta-catenin in the inulin (3.15+/-2.9 relative units) and inulin/rye (5.17+/-6.94 relative units) groups was also significantly higher (P=0.003-0.009) in the adenoma tissue when compared with the surrounding mucosa (0.5+/-0.5 and 0.35+/-0.39 relative units). However, HMR was able to restore nuclear beta-catenin level of the adenoma tissue (0.41+/-0.25 relative units) to the level found in the surrounding mucosa (0.36+/-0.28 relative units).

Topics: Adenoma; Adenomatous Polyposis Coli; Animals; beta Catenin; Body Weight; Cell Nucleus; Cytoskeletal Proteins; Cytosol; Furans; Intestinal Mucosa; Intestinal Neoplasms; Intestine, Small; Inulin; Lignans; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Neoplasms, Experimental; Plant Extracts; Secale; Trans-Activators

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

A diphyllin glycoside called cleistanthin A was isolated from the tropical plant Cleistanthus collinus and its anticancer potential was assessed. This compound showed preferential cytotoxicity in several tumor cell lines. The GI50 values for normal cell lines were between 10(-6) and 10(-7) M while for tumor cells the values ranged from 10(-7) to 10(-9) M. When the cytotoxicity of this compound was compared with five anticancer drugs, cleistanthin A was found to be most effective for the oral carcinoma cell line KB and the cervical carcinoma cell line SiHa. The efficacy of cleistanthin A in arresting tumor growth was assessed in mice harboring Dalton's ascites lymphoma and a solid tumor S-180 sarcoma. In both cases, the tumor volume was drastically reduced upon treatment with cleistanthin A. This compound also increased the life span of mice with S-180 sarcoma to a similar extent as that done by cisplatin (CDDP: cis-diamminedichloroplatinum) and etoposide. However, cleistanthin A was less toxic than these drugs because it did not affect the body weight and lymphocyte count in treated animals. Although the molecular mechanisms of action of cleistanthin A in arresting cell growth are yet to be explored in various perspectives, our present results indicate that this compound arrests growth by inhibiting DNA synthesis and cell division and by driving cells to apoptosis. Time-lapse video microscopic recordings of cleistanthin A-treated cells showed vigorous membrane blebbing, characteristic of apoptosis.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Body Weight; Drug Screening Assays, Antitumor; Fibroblasts; Glycosides; Humans; Leukocytes; Lignans; Lymphocytes; Mice; Rats; Tumor Cells, Cultured

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

Flaxseed is the richest source of the mammalian lignan precursor secoisolariciresinol diglycoside (SDG). Because lignans have estrogen agonist or antagonist properties, the objective of this study was to determine whether feeding flaxseed to rats during a hormone-sensitive period has reproductive effects. Rat dams were fed a basal diet or the basal diet supplemented with 10% flaxseed, 5% flaxseed or SDG at the level in 5% flaxseed during pregnancy and lactation. At weaning, the offspring were fed the basal diet. Flaxseed had no effect on pregnancy outcome except that the 10% flaxseed diet lowered birth weight (P < 0.05), compared with other treatments, and produced hormonal effects. The female offspring had shortened anogenital distance, greater uterine and ovarian relative weights, earlier age and lighter body weight at puberty, lengthened estrous cycle and persistent estrus (P < 0.05), whereas the males had reduced postnatal weight gain and, at postnatal d 132, greater sex gland and prostate relative weights (P < 0.05), suggesting estrogenic effects. In contrast, compared with the basal diet, 5% flaxseed reduced immature ovarian relative weight by 29% (P < 0.05), delayed puberty by approximately 5 d (P < 0.05) and tended to lengthen diestrus, indicating an antiestrogenic effect. The SDG produced results similar to those of 5% flaxseed, suggesting that lignans were responsible for the observed effects. Lignans were transferred to the offspring via rat dam's milk as indicated by the recovery of radioactivity in the offspring of lactating dams given 3H-SDG. Because flaxseed affects the reproductive development of offspring, caution is suggested when consuming flaxseed during pregnancy and lactation.

Topics: Anal Canal; Animals; Body Weight; Butylene Glycols; Diet; Estrus; Female; Flax; Genitalia; Lignans; Male; Milk; Organ Size; Pregnancy; Pregnancy Outcome; Prostate; Rats; Rats, Sprague-Dawley; Reproduction

Flaxseed, the richest source of mammalian lignan precursors, such as secoisolariciresinol diglycoside (SD), has been shown over the short term to decrease some early markers of colon cancer risk. This study determined whether over the long term flaxseed still exerts a colon cancer protective effect, whether its effect may, in part, be due to its high content of SD and whether any change in beta-glucuronidase activity plays a role in the protective effect. Six groups of male Sprague-Dawley rats were fed for 100 days either a basal high fat (20%) diet (BD), BD supplemented with 2.5 or 5% flaxseed or 2.5 or 5% defatted flaxseed (equivalent to the respective flaxseed diets) or BD with a daily gavage of 1.5 mg SD. All rats were injected with a single dose of azoxymethane (15 mg/kg body wt) 1 week prior to commencing the dietary treatments. Urinary lignan excretion, which is an indicator of mammalian lignan production, was significantly increased in the flaxseed and defatted flaxseed groups. The total activity of cecal beta-glucuronidase was significantly increased in a dose-dependent manner by the flaxseed and defatted flaxseed diet groups. Compared with the control the number of aberrant crypts per focus was significantly reduced in the distal colon of the treated rats. Four microadenomas and two polyps were observed in the control group, but not in the treated groups. The total activity of beta-glucuronidase was positively correlated with total urinary lignan excretion and negatively with the total number of aberrant crypts and the total number of aberrant crypt foci in the distal colon. There were no significant differences between the flaxseed and the corresponding defatted flaxseed groups. It is concluded that flaxseed has a colon cancer protective effect, that it is due, in part, to SD and that the protective effect of flaxseed is associated with increased beta-glucuronidase activity.

Topics: Animals; Anticarcinogenic Agents; Body Weight; Butylene Glycols; Cecum; Colonic Neoplasms; Eating; Fatty Acids; Glucosides; Glucuronidase; Hydrogen-Ion Concentration; Lignans; Male; Organ Size; Plant Extracts; Precancerous Conditions; Rats; Rats, Sprague-Dawley; Seeds

Lignans and isoflavonoids are diphenolic compounds found in plant foods, particularly whole grains and legumes. They have been shown to have anticarcinogenic properties in animal and cell studies, and have been associated with reduced cancer risk in epidemiological studies. In order to perform further epidemiological and metabolic studies on these compounds, it is necessary to be able to monitor concentrations in biological samples. In this study, we examined the effects of consumption of flaxseed, a concentrated source of lignans, on fecal lignan excretion and evaluated the effect of high lignan consumption on fecal excretion of isoflavonoids. Thirteen women were studied for two diet periods of three menstrual cycles each in a cross-over design. During the control period, they consumed their usual diets; during the treatment period they consumed their usual diets supplemented with 10 g/day ground flaxseed. Feces were collected on days 7-11 of the last menstrual cycle in each diet period. Five-day fecal composites were analyzed for lignans and isoflavonoids by isotope dilution gas chromatography-mass spectrometry. Fecal excretion of the lignans enterodiol, enterolactone, and matairesinol increased significantly with flax consumption, from 80.0 +/- 80.0 (SD) to 2560 +/- 3100; 640 +/- 480 to 10,300 +/- 7580; and 7.33 +/- 10.0 to 11.9 +/- 8.06 nmol/day, respectively. There were no differences in fecal excretion of the isoflavonoids, daidzein, equol, genistein, and O-demethylangolensin.

Topics: Adult; Body Weight; Diet; Feces; Female; Flavonoids; Humans; Lignans; Premenopause; Seeds

Long Evans Cinnamon (LEC) rats, that spontaneously develop hepatitis, were found to possess autoantibodies to liver microsomal proteins (anti-LM) before the development of hepatitis. Anti-LM antibody was assumed to appear in association with the lethal hepatitis in the LEC rats. Thus, the purpose of this study was to investigate the effects of an anti-hepatitis drug on the development of hepatitis and the occurrence of the antibody in LEC rats. Mortality, blood biochemical parameters and the titer of serum anti-LM antibody were measured. In control LEC rats, 4 of 8 rats died before 20 weeks of age. In rats treated with TJN-101 ((+)-(6S,7S,R-biar)-5,6,7,8-tetrahydro-1,2,3,12-tetramethoxy -6,7-dimethyl-10,11 - methylenedioxy-6-dibenzo[a,c]cyclooctenol), 4 of 7 rats died of hepatitis, but the time of death was delayed by 7-10 weeks compared to the control rats. The titer of the anti-LM antibody increased 3-7 weeks before death in the non-survivors in control and TJN-101-treated rats, supporting the idea that anti-LM antibody occurs in association with acute lethal hepatitis.

Topics: Animals; Autoantibodies; Autoimmune Diseases; Body Weight; Cyclooctanes; Dioxoles; Enzyme-Linked Immunosorbent Assay; Female; Hepatitis, Animal; Lignans; Microsomes, Liver; Rats

The effects of gomisin A, a lignan component of Schizandra fruits, on the promotion stage of hepatocarcinogenesis initiated by 3'-methyl-4-dimethylamino-azobenzene (3'-MeDAB) in male Donryu rats were investigated. When different types of tumor promotors, phenobarbital (PB) and deoxycholic acid (DCA), were administered for 5 weeks after initiation by 3'-MeDAB, preneoplastic alterations in the liver, determined by glutathione S-transferase placental form (GST-P), were markedly increased. Gomisin A significantly inhibited the increase in number and size of GST-P positive foci, regardless of the promotor. This lignan inhibited the increase in serum bile acid concentration by administration of DCA, but hardly influenced the serum bile acids in the PB-combined group. These results suggest that the inhibitory effect of gomisin A on the promotive action of DCA is based on improving bile acid metabolism, but regarding the action of PB, the effect could not be elucidated from the metabolism of bile acids.

Topics: Animals; Anticarcinogenic Agents; Bile Acids and Salts; Body Weight; Carcinogens; Cyclooctanes; Deoxycholic Acid; Dioxoles; Immunohistochemistry; Lignans; Liver Neoplasms, Experimental; Male; Methyldimethylaminoazobenzene; Organ Size; Phenobarbital; Rats

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 effects of gomisin A, a lignan component of Schizandra fruits, on development of preneoplastic lesions in the liver after a short-term (3 weeks) feeding of 3'-methyl-4-dimethyl-aminoazobenzene (3'-MeDAB) to male Donryu rats were investigated, and compared with the effects of phenobarbital. Gomisin A inhibited both increases of the level of glutathione-S-transferase placental form (GST-P) and the number and size of GST-P positive foci in the liver increased after treatment with 3'-MeDAB. Moreover, although the population of diploid nuclei was increased and that of tetraploid nuclei was decreased by pretreatment with 3'-MeDAB, gomisin A returned this to near the normal ploidy pattern. But phenobarbital increased the level of GST-P and the number and size of GST-P positive foci with little affect on the ploidy population changed by 3'-MeDAB. Thus, the effect of gomisin A on hepatocarcinogenesis was inhibitory in contrast with that of phenobarbital. This study suggests that gomisin A is a candidate for a chemopreventive drug inhibiting the promotion process in hepatocarcinogenesis.

Topics: Animals; Anticarcinogenic Agents; Body Weight; Cell Nucleus; Cyclooctanes; Dioxoles; Drugs, Chinese Herbal; Glutathione Transferase; Isoenzymes; Lignans; Liver; Liver Neoplasms, Experimental; Male; Methyldimethylaminoazobenzene; Organ Size; Phenobarbital; Ploidies; Precancerous Conditions; Rats

Topics: Adaptation, Psychological; Animals; Body Temperature; Body Weight; Cold Temperature; Cyclooctanes; Drug Evaluation, Preclinical; Drugs, Chinese Herbal; Electrocardiography; Heart Rate; Lignans; Male; Panax; Plants, Medicinal; Polycyclic Compounds; Rats; Rats, Sprague-Dawley; Respiration; Restraint, Physical; Stress, Psychological

We examined the effects of gomisin A on tumor promotion in the liver after a short-term feeding of 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB) to rats, compared with the effects of phenobarbital. Male Donryu rats were fed ad libitum a diet containing 0.06% 3'-MeDAB and 0.03% or 0.01% gomisin A or water containing 0.05% phenobarbital. Gomisin A and phenobarbital did not cause any proliferative and neoplastic lesions by themselves in 40 weeks of feeding. Altered foci in the liver increased with a peak at 12 weeks after the rats were fed 3'-MeDAB. Gomisin A decreased the number of hepatic altered foci such as the clear cell and basophilic cell type foci in the early stages. Phenobarbital enhanced neoplastic alterations so that the number and size of the foci were much larger in the phenobarbital-combined group than in the 3'-MeDAB-control group. Thus, phenobarbital acted as a promoter of cells initiated by 3'-MeDAB; on the other hand, gomisin A showed a weak suppressive effect on tumor promotion.

Topics: Animals; Anticarcinogenic Agents; Body Weight; Cyclooctanes; Dioxoles; Lignans; Liver Neoplasms, Experimental; Male; Methyldimethylaminoazobenzene; Molecular Structure; Organ Size; Phenobarbital; Polycyclic Compounds; Rats; Rats, Inbred Strains