gamma-sitosterol and Inflammation

While many factors are involved in the etiology of cancer, it has been clearly established that diet significantly impacts one's risk for this disease. More recently, specific food components have been identified which are uniquely beneficial in mitigating the risk of specific cancer subtypes. Plant sterols are well known for their effects on blood cholesterol levels, however research into their potential role in mitigating cancer risk remains in its infancy. As outlined in this review, the cholesterol modulating actions of plant sterols may overlap with their anti-cancer actions. Breast cancer is the most common malignancy affecting women and there remains a need for effective adjuvant therapies for this disease, for which plant sterols may play a distinctive role.

Topics: Anticholesteremic Agents; Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Membrane; Cholesterol; Estrogens; Female; Glucose; Humans; Immunity; Inflammation; Liver X Receptors; Orphan Nuclear Receptors; Oxidative Stress; Phytosterols; Receptors, Estrogen; Risk Factors; Signal Transduction; Sitosterols

The physiological roles of phytosterols in chronic inflammation, which are believed to be involved in the underlying mechanisms for metabolic diseases, have yet to be elucidated. Therefore, in the present study, we aimed to elucidate the physiological roles of phytosterols in both clinical studies and animal experiments. We observed the existence of rather specific negative correlations between the serum sitosterol level and the serum IL-6 and the TNF-α levels in both diabetic subjects (n=46) and non-diabetic subjects (n=178). Multiple regression analyses also revealed that the serum IL-6 and TNF-α levels exhibited strong negative correlations with the serum sitosterol levels. When ABCG5/8 KO mice with markedly elevated plasma sitosterol levels and ABCG5/8 hetero mice were fed a high-fat diet, we observed that the increase in body weight, the fatty liver changes, and the expansion of perigonadal adipose tissues were suppressed in ABCG5/8 KO mice without any modulation of food intake. We also observed that the plasma IL-6 and TNF-α levels, the expressions of TNF-α and PAI-1 in the liver and the expressions of the IL-6, TNF-α, and MCP-1 levels in the adipose tissue were lower in ABCG5/8 KO mice. These results suggest that sitosterol might suppress obesity-related chronic inflammation and might be applicable to the treatment of metabolic diseases.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily G, Member 5; Chronic Disease; Female; Humans; Inflammation; Interleukin-6; Lipoproteins; Male; Mice; Mice, Knockout; Middle Aged; Obesity; Sitosterols; Tumor Necrosis Factor-alpha

High-risk subjects with elevated C-reactive protein (CRP) are at high risk for cardiovascular events and frequently require potent statins or combined lipid-lowering therapy to achieve lipid targets and decrease inflammation. Our study aimed at evaluating the effects of three lipid-modifying therapies on LDL-cholesterol, CRP levels and markers of cholesterol absorption and synthesis.. A prospective intervention study was performed in high cardiovascular risk individuals receiving atorvastatin 10mg daily for four weeks. Those with CRP≥2.0mg/L were randomized to another four-week treatment period with atorvastatin 40mg, ezetimibe 10mg or the combination of atorvastatin 40mg / ezetimibe 10mg. Lipids, markers of cholesterol absorption (campesterol and β-sitosterol), and synthesis (desmosterol), as well as CRP were quantified at baseline and end of study.. One hundred and twenty two individuals were included. Atorvastatin alone or combined with ezetimibe reduced both LDL-cholesterol and CRP (P<0.002 vs. baseline; Wilcoxon); ezetimibe did not modify CRP. Ezetimibe-based therapies reduced absorption markers and their ratios to cholesterol (P<0.0001 vs. baseline, for all; Wilcoxon), whereas atorvastatin alone increased campesterol/cholesterol and β-sitosterol/cholesterol ratios (P<0.05 vs. baseline; Wilcoxon). In addition, ezetimibe also increased desmosterol and desmosterol/cholesterol ratio (P<0.0001 vs. baseline; Wilcoxon).. These results contribute to understanding the link between cellular cholesterol homeostasis, inflammation and lipid-modifying therapies. Our findings highlight the broader benefit of combined therapy with a potent statin and ezetimibe decreasing inflammation, and preventing increase in cholesterol biosynthesis, an effect not observed with ezetimibe alone.

Topics: Aged; Anticholesteremic Agents; Atorvastatin; Azetidines; C-Reactive Protein; Cardiovascular Diseases; Cholesterol; Desmosterol; Ezetimibe; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Male; Middle Aged; Phytosterols; Prospective Studies; Pyrroles; Risk Factors; Sitosterols; Statistics, Nonparametric

A pilot study was undertaken to investigate the effects of the intake of capsules containing the plant sterols and sterolins (BSS:BSSG mixture) on selected immune parameters of volunteers participating in an ultra-marathon in Cape Town, South Africa. Those runners having received active capsules (n=9) showed less neutrophilia, lymphopenia and leukocytosis when compared to their counterparts having received placebo capsules (n=8): the placebo treated individuals showed significant increases in their total white blood cell numbers as well as in their neutrophils (p=0.03 and 0.03 respectively). Furthermore, statistically significant increases within lymphocyte subsets were observed in the runners having received the active capsules: CD3+ cells increased (p=0.02) as did CD4+ cells (p=0.03). In parallel, the BSS:BSSG capsules decreased the plasma level of IL6 in the runners using the active capsules (p=0.08) and significantly decreased the cortisol: DHEAs ratio (p=0.03), suggesting that these volunteers had less of an inflammatory response and were less immune suppressed during the post-marathon recovery period. These findings justify further investigations into the use of the phytosterols to prevent the subtle immunosuppression associated with excessive physical stress.

Topics: Adult; Blood Cell Count; Dietary Supplements; Exercise; Female; Humans; Immunosuppression Therapy; Inflammation; Leukocytosis; Lymphocyte Subsets; Lymphopenia; Male; Middle Aged; Neutrophils; Phytosterols; Sitosterols

We previously demonstrated that β-sitosterol (BSS) inhibits the expression of the chemokine IL-8 in CF bronchial epithelial cells exposed to P. aeruginosa. In the mouse model of lung chronic infection, herein shown, BSS significantly reduced leukocyte recruitment in the bronchoalveolar lavage fluid and decreased bacteria recovered in the airways. Treatment with BSS decreased the expression of key cytokines involved in immune response, mainly neutrophil chemotaxis, in the lung homogenate. This anti-inflammatory activity is accompanied by a beneficial protecting activity against infection and improvement of health status. Our data suggest that BSS has the potential to become a new drug to target the excessive neutrophil recruitment in lungs chronically infected by P. aeruginosa and encourage future investigations on mechanism of protection driven by BSS.

Topics: Animals; Cystic Fibrosis; Disease Models, Animal; Inflammation; Lung; Mice; Neutrophils; Pneumonia; Pseudomonas aeruginosa; Pseudomonas Infections

In most asthma patients, symptoms are controlled by treatment with glucocorticoid, but long-term or high-dose use can produce adverse effects. Therefore, it is crucial to find new therapeutic strategies. β-sitosterol could suppress type Ⅱ inflammation in ovalbumin (OVA)-induced mice, but its mechanisms have remained unclear.. A binding activity of β-sitosterol with glucocorticoid receptor (GR) was analyzed by molecular docking. Human bronchial epithelial cells (BEAS-2B) and human bronchial smooth muscle cells (HBSMC) were treated with different concentrations (0, 1, 5, 10, 20, and 50 μg/mL) of β-sitosterol for suitable concentration selection. In transforming growth factor (TGF)-β1 treated BEAS-2B and HBSMC, cells were treated with 20 μg/mL β-sitosterol or dexamethasone (Dex) to analyze its possible mechanism. In OVA-induced mice, 2.5 mg/kg β-sitosterol or Dex administration was performed to analyze the therapeutic mechanism of β-sitosterol. A GR antagonist RU486 was used to confirm the mechanism of β-sitosterol in the treatment of asthma.. A good binding of β-sitosterol to GR (score = -8.2 kcal/mol) was found, and the GR expression was upregulated with β-sitosterol dose increase in BEAS-2B and HBSMC. Interleukin (IL)-25 and IL-33 secretion was significantly decreased by β-sitosterol in the TGF-β1-induced BEAS-2B, and the levels of collagen 1A and α-smooth muscle actin (SMA) were reduced in the TGF-β1-induced HBSMC. In the OVA-challenged mice, β-sitosterol treatment improved airway inflammation and remodeling through suppressing type Ⅱ immune response and collagen deposition. The therapeutic effects of β-sitosterol were similar to Dex treatment in vitro and in vivo. RU486 treatment clearly hampered the therapeutic effects of β-sitosterol in the TGF-β1-induced cells and OVA-induced mice.. This study identified that β-sitosterol binds GR to perform its functions in asthma treatment. β-sitosterol represent a potential therapeutic drug for allergic asthma.

Topics: Airway Remodeling; Animals; Asthma; Collagen; Disease Models, Animal; Humans; Inflammation; Lung; Mice; Mice, Inbred BALB C; Mifepristone; Molecular Docking Simulation; Ovalbumin; Receptors, Glucocorticoid; Sitosterols; Transforming Growth Factor beta1

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic hepatic disorder. The naturally occurring phytosterol; β-sitosterol has antiobesogenic and anti-diabetic properties. The purpose of this study was to explore the role of β-sitosterol in preventing hepatic steatosis induced by a high-fat diet (HFD) in rats. In the current study, to induce NAFLD in the female Wister rats, an HFD was administered to them for 8 weeks. The pathogenic severity of steatosis in rats receiving an HFD diet was dramatically decreased by oral administration of β-sitosterol. After administering β-sitosterol to HFD-induced steatosis for three weeks, several oxidative stress-related markers were then assessed. We showed that β-sitosterol reduced steatosis and the serum levels of triglycerides, transaminases (ALT and AST) and inflammatory markers (IL-1β and iNOS) compared to HFD-fed rats. Additionally, β-sitosterol reduced endoplasmic reticulum stress by preventing the overexpression of inositol-requiring enzyme-1 (IRE-1α), X-box binding protein 1(sXBP1) and C/EBP homologous protein (CHOP) genes which, showing a function in the homeostatic regulation of protein folding. Also, it was found that the expression of the lipogenic factors; peroxisome proliferator-activated receptor (PPAR-α), sterol regulatory element binding protein (SREBP-1c) and carnitine palmitoyltransferase-1(CPT-1), which are involved in the regulation of the fatty acid oxidation process, may be regulated by β-sitosterol. It can be concluded that β-sitosterol may prevent NAFLD by reducing oxidative stress, endoplasmic reticulum stress and inflammatory responses, which supports the possibility of using β-sitosterol as an alternative therapy for NAFLD. Together, β-sitosterol may be an option for NAFLD prevention.

Topics: Animals; Diet, High-Fat; Female; Inflammation; Lipid Metabolism; Liver; Non-alcoholic Fatty Liver Disease; Rats; Rats, Wistar

β-sitosterol, a natural plant steroid, has been shown to promote anti-inflammatory and antioxidant activities in the body. In this study, β-sitosterol was used to protect against lipopolysaccharide (LPS)-induced cell damage in bovine mammary epithelial cells, which are commonly studied as a cell model of mammary inflammatory response and lipogenesis. Results showed that treatment with a combination of LPS and β-sitosterol significantly reduced oxidative stress and inflammation, while increasing the expression of anti-apoptotic proteins and activating the hypoxia-inducible factor-1(HIF-1α)/mammalian target of rapamycin(mTOR) signaling pathway to inhibit apoptosis and improve lipid synthesis-related gene expression. Our finding suggests that β-sitosterol has the potential to alleviate inflammation in the mammary gland.

Topics: Animals; Cattle; Epithelial Cells; Inflammation; Lipogenesis; Lipopolysaccharides; Mammals; Mammary Glands, Animal

Putrajeevak (

Topics: Animals; Chromatography, Supercritical Fluid; Disease Models, Animal; Euphorbiaceae; Fatty Acids; Female; Fertility; Inflammation; Male; Ovary; Ovum; Pelvis; Plant Oils; Seeds; Sitosterols; Testis; Zebrafish

β-sitosterol (SIT), the most abundant bioactive component of vegetable oil and other plants, is a highly potent antidiabetic drug. Our previous studies show that SIT controls hyperglycemia and insulin resistance by activating insulin receptor and glucose transporter 4 (GLUT-4) in the adipocytes of obesity induced type 2 diabetic rats. The current research was undertaken to investigate if SIT could also exert its antidiabetic effects by circumventing adipocyte induced inflammation, a key driving factor for insulin resistance in obese individuals. Effective dose of SIT (20 mg/kg b.wt) was administered orally for 30 days to high fat diet and sucrose induced type-2 diabetic rats. Metformin, the conventionally used antidiabetic drug was used as a positive control. Interestingly, SIT treatment restores the elevated serum levels of proinflammatory cytokines including leptin, resistin, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) to normalcy and increases anti-inflammatory adipocytokines including adiponectin in type 2 diabetic rats. Furthermore, SIT decreases sterol regulatory element binding protein-1c (SREBP-1c) and enhances Peroxisome Proliferator-activated receptor-γ (PPAR-γ) gene expression in adipocytes of diabetic rats. The gene and protein expression of c-Jun-N-terminal kinase-1 (JNK1), inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) and nuclear factor kappa B (NF-κB) were also significantly attenuated in SIT treated groups. More importantly, SIT acts very effectively as metformin to circumvent inflammation and insulin resistance in diabetic rats. Our results clearly show that SIT inhibits obesity induced insulin resistance by ameliorating the inflammatory events in the adipose tissue through the downregulation of IKKβ/NF-κB and c-Jun-N-terminal kinase (JNK) signaling pathway.

Topics: Adipocytes; Adipokines; Adipose Tissue; Animals; Body Weight; Cytokines; Diabetes Mellitus, Type 2; Diet, High-Fat; Down-Regulation; Feeding Behavior; I-kappa B Kinase; Inflammation; Inflammation Mediators; Insulin Resistance; Male; MAP Kinase Signaling System; Molecular Docking Simulation; NF-kappa B; Obesity; PPAR gamma; Rats; RNA, Messenger; Sitosterols; Sterol Regulatory Element Binding Protein 1; Sucrose; Up-Regulation

Chorioamnionitis can lead to inflammation and injury of the liver and gut, thereby predisposing patients to adverse outcomes such as necrotizing enterocolitis (NEC). In addition, intestinal bile acids (BAs) accumulation is causally linked to NEC development. Plant sterols are a promising intervention to prevent NEC development, considering their anti-inflammatory properties in the liver. Therefore, we investigated whether an intra-amniotic (IA)

Topics: Animals; beta-Cyclodextrins; Cholesterol; Chorioamnionitis; Disease Models, Animal; Drug Carriers; Enterocolitis, Necrotizing; Enterohepatic Circulation; Female; Fetus; Inflammation; Injections, Intralesional; Liver; Phytosterols; Phytotherapy; Post-Exposure Prophylaxis; Pregnancy; Sheep; Sitosterols; Ureaplasma; Ureaplasma Infections

β-Sitosterol (24-ethyl-5-cholestene-3-ol) is a common phytosterol Chinese medical plants that has been shown to possess antioxidant and anti-inflammatory activity. In this study we investigated the effects of β-sitosterol on influenza virus-induced inflammation and acute lung injury and the molecular mechanisms. We demonstrate that β-sitosterol (150-450 μg/mL) dose-dependently suppresses inflammatory response through NF-κB and p38 mitogen-activated protein kinase (MAPK) signaling in influenza A virus (IAV)-infected cells, which was accompanied by decreased induction of interferons (IFNs) (including Type I and III IFN). Furthermore, we revealed that the anti-inflammatory effect of β-sitosterol resulted from its inhibitory effect on retinoic acid-inducible gene I (RIG-I) signaling, led to decreased STAT1 signaling, thus affecting the transcriptional activity of ISGF3 (interferon-stimulated gene factor 3) complexes and resulting in abrogation of the IAV-induced proinflammatory amplification effect in IFN-sensitized cells. Moreover, β-sitosterol treatment attenuated RIG-I-mediated apoptotic injury of alveolar epithelial cells (AEC) via downregulation of pro-apoptotic factors. In a mouse model of influenza, pre-administration of β-sitosterol (50, 200 mg·kg

Topics: A549 Cells; Acute Lung Injury; Animals; Antiviral Agents; Apoptosis; DEAD Box Protein 58; Dogs; Female; HEK293 Cells; Humans; Inflammation; Influenza A Virus, H1N1 Subtype; Interferon Lambda; Interferon Type I; Interferons; Lung; Madin Darby Canine Kidney Cells; Mice, Inbred BALB C; Plants; Signal Transduction; Sitosterols; STAT1 Transcription Factor

To explore the molecular mechanism of Simiao powder in the treatment of knee osteoarthritis.. Based on oral bioavailability and drug-likeness, the main active components of Simiao powder were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). GeneCard, OMIM, DisGeNET, DrugBank, PharmGkb, and the Therapeutic Target Database were used to establish target databases for knee osteoarthritis. Cytoscape software was used to construct a visual interactive network diagram of "active ingredient - action target - disease." The STRING database was used to construct a protein interaction network and analyze related protein interaction relationships. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) biological process enrichment analysis were performed on the core targets. Additionally, Discovery Studio software was used for molecular docking verification of active pharmaceutical ingredients and disease targets.. Thirty-seven active components of Simiao powder were screened, including 106 common targets. The results of network analysis showed that the targets were mainly involved in regulating biological processes such as cell metabolism and apoptosis. Simiao powder components were predicted to exert their therapeutic effect on the AGE-RAGE signaling pathway in diabetic complications, IL-17 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, and HIF-1 signaling pathway. The molecular docking results showed that the active components of Simiao powder had a good match with the targets of IL1B, MMP9, CXCL8, MAPK8, JUN, IL6, MAPK1, EGF, VEGFA, AKT1, and PTGS2.. Simiao powder has multisystem, multicomponent, and multitarget characteristics in treating knee osteoarthritis. Its possible mechanism of action includes inhibiting the inflammatory response, regulating immune function, and resisting oxidative stress to control the occurrence and development of the disease. Quercetin, wogonin, kaempferol, beta-sitosterol, and other active ingredients may be the material basis for the treatment of knee osteoarthritis.

Topics: Administration, Oral; Apoptosis; Drugs, Chinese Herbal; Flavanones; Humans; Inflammation; Kaempferols; Medicine, Chinese Traditional; Molecular Docking Simulation; Osteoarthritis, Knee; Oxidative Stress; Powders; Quercetin; Reproducibility of Results; Signal Transduction; Sitosterols; Software

In this article, we aim to examine the novel effects of β-sitosterol on murine experimental colitis. β-Sitosterol significantly reduces the weight loss, colon length, and alleviated microscopic appearances of colitis induced by dextran sulfate sodium. This compound also decreases the levels of TNF-α, IL-6, and IL-1β in intestinal tissue of mice with experimental colitis in a concentration-dependent manner. β-Sitosterol treatment to intestinal epithelial cells significantly increases expression of antimicrobial peptides and reduces survival of intracellular Salmonella typhimurium. These results showed the multiple effects of β-sitosterol against pathogenic bacteria for a novel approach to the treatment of colonic inflammation.

Topics: Animals; Colitis; Dextran Sulfate; Disease Models, Animal; Hypolipidemic Agents; Inflammation; Intestinal Mucosa; Male; Mice; Mice, Inbred C57BL; Salmonella typhimurium; Sitosterols; Typhoid Fever

Aberrant epigenetic modifications are responsible for tumor development and cancer progression; however, readily reversible. Bioactive molecules from diets are promising to cure cancer by modulating epigenetic marks and changing immune response. These compounds specifically target the activity of DNMTs and HDACs to cure various human cancers. In view of this, we investigated the anticancer and epigenetic regulatory activities of an edible-plant Paederia foetida. The efficacy of methanolic extract of P. foetida leaves (MEPL) was tested for the modulation of epigenetic factors in gene silencing, i.e. DNMT and HDAC and expression pattern of certain tumor-suppressor genes. After treatment of prostate cancer cells (PC-3 and DU-145) with MEPL, lupeol and β-sitosterol; induction of apoptosis, decrease in cellular-viability and inhibition of cellular-migration were noticed. Simultaneously there was inhibition of DNMT1, HDACs and pro-inflammatory, IL-6, IL1-β, TNF-α and anti-inflammatory, IL-10 genes in cancer and THP1 cell lines. The DNMT1 protein content, enzyme activity and Bcl2 expression decreased significantly; however, expression of E-cadherin (CDH1) and pro-apoptotic gene Bax increased significantly after the treatment of cells with drugs. We conclude plant-derived compounds can be considered to target epigenetic machineries involved with malignant transformation and can open new avenues for cancer therapeutics provoking immune response.

Topics: Cell Line, Tumor; Cell Survival; DNA (Cytosine-5-)-Methyltransferase 1; Gene Expression Regulation, Neoplastic; Histone Deacetylase 1; Histone Deacetylase 2; Humans; Inflammation; Male; Pentacyclic Triterpenes; Phytochemicals; Plant Extracts; Plant Leaves; Prostatic Neoplasms; RNA, Messenger; Rubiaceae; Sitosterols

Beta-sitosterol (Sit) widely exists in natural plants, is classed as phytosterol and known as the "key of life". Most pharmacological studies and clinical applications are limited because of the fact that Sit is difficult to be solved. Therefore, it is viable to enhance pharmacologic activities of Sit by using its derivatives which can be obtained through the modification of Sit. In this study, 4 kinds of new Sit derivatives were obtained by the esterification reaction. Further, the hepatoprotective effects of Sit and its derivatives were investigated against acute liver injury induced by lipopolysaccharide/d-galactosamine (LPS/GalN) in mice and its mechanism was illustrated by western blot analysis and real-time PCR. The results demonstrated that among its derivatives, 2-naphthoyl Sit ester (Sit-N) (50 mg/kg) showed the strongest activities against acute liver injury. Final experimental results showed that Sit-N significantly decreased the serum activity of aspartate transaminase (AST) and alanine aminotransferase (ALT); Sit-N also markedly reduced tumor necrosis factor (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels. Meanwhile, Sit-N drastically improved the activities of antioxidant enzymes such as superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT), and suppressed the expression of malondialdehyde (MDA). Results also displayed that over-expression of Toll like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) induced by LPS/Gal N were inhibited by Sit-N. Meanwhile, the expression of nuclear respiratory factor2 (Nrf2) and heme oxygenase-1 (HO-1) were enhanced. The results all above verified the effectiveness of Sit-N against acute liver injury induced by LPS/GalN mediated by TLR4 and Nrf2 pathways.

Topics: Animals; Anti-Inflammatory Agents; Cell Survival; Chemical and Drug Induced Liver Injury; Dose-Response Relationship, Drug; Galactosamine; Inflammation; Lipopolysaccharides; Mice; Molecular Structure; Oxidation-Reduction; Sitosterols; Structure-Activity Relationship

Topics: Analgesics; Anti-Inflammatory Agents; Apocynaceae; Cytokines; Fatty Acids, Unsaturated; Glucosides; Humans; Inflammation; Interleukin-6; Leukocytes, Mononuclear; Lipopolysaccharides; Macrophages; Molecular Docking Simulation; Nociceptive Pain; Pain Perception; Plant Extracts; Plant Roots; Sitosterols; Steroids; Stigmasterol; Tumor Necrosis Factor-alpha

Nepeta deflersiana (Lamiaceae) is a perennial herb used in the Saudi and Yemeni folk medicine as an anti-inflammatory, carminative, and antirheumatic agent.. This study explores the phytochemistry of the plant and the cardioprotective effect of N. deflersiana ethanolic extract (NDEE) against isoproterenol (ISP)-induced myocardial injury in rats.. Cardiac function, serum cardiac enzymes, myocardial antioxidants, inflammatory, and apoptotic biomarkers, and histopathological parameters were studied in ISP-injured Wistar rat heart tissues.. To the best of our knowledge, this is the first study to report the isolation of nine secondary metabolites from this plant: 1α-hydroxy-7α,14α,18-triacetoxy-isopimara-8,15-diene (1), β-sitosterol (2), lupeol (3), ursolic acid (4), 2,3-dihydroxy ursolic acid (5), caffeic acid (6), methyl rosmarinate (7), rosmarinic acid (8), and an irridoid glucoside 8-epi-7-deoxyloganic acid (9). To explain the mechanisms underlying the cardioprotective effect of NDEE, we evaluated the redox-sensitivity of NDEE in ISP-induced cardiac injury. The oral administration of NDEE (50 and 100 mg/kg b.w) prevented the depletion of endogenous antioxidants (CAT, SOD, NP-SH, and NO) and myocyte injury marker enzymes and inhibited lipid peroxidation (MDA, MPO). Moreover, NDEE downregulated the expression of pro-inflammatory cytokines (TNFα, IL-6, and IL-10) and apoptotic markers (caspase-3 and Bax) and upregulated the anti-apoptotic protein Bcl2. Furthermore, NDEE pretreatment significantly downregulated cardiac NF-κB (p65) expression, NF-κB-DNA binding activity, and MPO activity. Histological data showed that NDEE pretreatment reduced myonecrosis, edema, and infiltration of inflammatory cells and restored the architecture of cardiomyocytes.. NDEE demonstrated strong antioxidant, cardioprotective, anti-inflammatory, and anti-apoptotic potential against myocardial damage. This further endorses the use of N. deflersiana in Yemeni folk medicine against cardiovascular diseases.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Caspase 3; Cytokines; Down-Regulation; Heart; Inflammation; Iridoids; Isoproterenol; Lipid Peroxidation; Male; Myocardium; Nepeta; NF-kappa B; Oxidative Stress; Plant Extracts; Rats; Rats, Wistar; Sitosterols

Parenteral plant sterols (PSs) are considered hepatotoxic; however, liver PSs and their associations with liver injury in patients with intestinal failure (IF) have not been reported.. We analyzed liver and serum PS (avenasterol, campesterol, sitosterol, and stigmasterol) concentrations and ratios to cholesterol and their associations with biochemical and histologic liver damage in children with IF during (n = 7) parenteral nutrition (PN) and after weaning off it (n = 9), including vegetable oil-based lipid emulsions.. Liver avenasterol, sitosterol, and total PS concentrations and cholesterol ratios were 2.4-fold to 5.6-fold higher in PN-dependent patients ( P < .05). Parenteral PS delivery reflected liver avenasterol and sitosterol ratios to cholesterol ( r = 0.83-0.89, P = .02-.04), while serum and liver total PS levels were positively interrelated ( r = 0.98, P < .01). Any liver histopathology was equally common while portal inflammation more frequent (57 vs 0%, P = .02) in PN-dependent patients. All liver PS fractions correlated positively with histologic portal inflammation ( r = 0.53-0.66, P < .05), and their total concentration was significantly ( P = .01) higher among patients with versus without portal inflammation. In PN-dependent patients, liver fibrosis and any histopathology correlated with liver campesterol and stigmasterol levels ( r = 0.79-0.87, P ≤ .03).. Among children with IF, parenteral PSs accumulate in the liver, reflect their increased serum levels, and relate with biochemical liver injury, portal inflammation, and liver fibrosis, thus supporting their role in promoting liver damage.

Topics: Alanine Transaminase; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Child; Child, Preschool; Cholesterol; Female; gamma-Glutamyltransferase; Humans; Infant; Inflammation; Intestinal Diseases; Liver; Male; Parenteral Nutrition; Phytosterols; Plant Oils; Portal Vein; Sitosterols; Stigmasterol; Triglycerides

The contribution of extra virgin olive oil (EVOO) macro- and micro-constituents in heart oxidative and inflammatory status in a hypercholesterolemic rat model was evaluated. Fatty acid profile as well as α-tocopherol, sterol, and squalene content was identified directly in rat hearts to distinguish the effect of individual components or to enlighten the potential synergisms.. Oils and oil-products with discernible lipid and polar phenolic content were used. Wistar rats were fed a high-cholesterol diet solely, or supplemented with one of the following oils, i.e., EVOO, sunflower oil (SO), and high-oleic sunflower oil (HOSO) or oil-products, i.e., phenolics-deprived EVOO [EVOO(-)], SO enriched with the EVOO phenolics [SO(+)], and HOSO enriched with the EVOO phenolics [HOSO(+)]. Dietary treatment lasted 9 weeks; at the end of the intervention blood and heart samples were collected.. High-cholesterol-diet-induced dyslipidemia was shown by increase in serum total cholesterol, low-density lipoprotein cholesterol, and triacylglycerols. Dyslipidemia resulted in increased malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) levels, while glutathione and interleukin 6 levels remained unaffected in all intervention groups. Augmentation observed in MDA and TNF-α was attenuated in EVOO, SO(+), and HOSO(+) groups. Heart squalene and cholesterol content remained unaffected among all groups studied. Heart α-tocopherol was determined by oil α-tocopherol content. Variations were observed for heart β-sitosterol, while heterogeneity was reported with respect to heart fatty acid profile in all intervention groups.. Overall, we suggest that the EVOO-polar phenolic compounds decreased MDA and TNF-α in hearts of cholesterol-fed rats.

Topics: alpha-Tocopherol; Animals; Cholesterol, Dietary; Cholesterol, HDL; Cholesterol, LDL; Diet; Diet, High-Fat; Dyslipidemias; Fatty Acids; Glutathione; Hypercholesterolemia; Inflammation; Interleukin-6; Male; Malondialdehyde; Olive Oil; Oxidative Stress; Phenols; Plant Oils; Rats; Rats, Wistar; Sitosterols; Sunflower Oil; Triglycerides; Tumor Necrosis Factor-alpha

The most abundant plant sterol β-sitosterol is widely used for treating heart diseases and chronic inflammatory conditions. The objective of the current study was to evaluate the nephroprotective effect of β-sitosterol against nephrotoxicants which were studied using renal function markers, antioxidant and lipid peroxidation status, and inflammatory markers.. Male albino Wistar rats were randomly grouped into four: group 1 was vehicle control rats (0.1% carboxymethyl cellulose [CMC]); group 2 was rats treated with N-diethylnitrosamine (DEN) (200 mg/kg body weight [bw] i.p. on the 15th day) and ferric nitrilotriacetate (Fe-NTA) (9 mg/kg bw i.p. on 30th and 32nd days); group 3 was rats that received β-sitosterol (20 mg/kg bw in 0.1% CMC, p.o. for 32 days) 2 weeks prior to the exposure to the nephrotoxicant; and group 4 was rats that received β-sitosterol alone. The experiment was terminated after the 24 h of last dosage of Fe-NTA, and all the animals were sacrificed. The blood, liver and kidney from each group were analyzed for biochemical, molecular and histological changes.. All the parameters showed significant changes in DEN and Fe-NTA treated animals, whereas β-sitosterol pretreated animals' altered biochemical parameters were restored to near normal. Histopathological and immunoexpression studies on tissues also corroborate the biochemical endpoints.. Administration of β-sitosterol to nephrotoxicity induced rats showed significant positive changes in biochemical parameters, histopathological and immunohistochemical observations, and up-regulation of Nrf2 gene expression. From this, it was clear that β-sitosterol showed renal protective function.

Topics: Animals; Antioxidants; Biomarkers; Diethylnitrosamine; Ferric Compounds; Inflammation; Kidney; Lipid Peroxidation; Liver; Male; Nitrilotriacetic Acid; Protective Agents; Rats; Rats, Wistar; Sitosterols; Up-Regulation

Patients with cardiac sarcoidosis (CS) suffer from myocardial inflammation, but atherosclerosis is not infrequent in these patients. However, the classical atherosclerotic risk factors, such as perturbed serum lipids and whole-body cholesterol metabolism, remain unravelled in CS.. We assessed serum non-cholesterol sterols, biomarkers of whole-body cholesterol synthesis and cholesterol absorption efficiency, with gas-liquid chromatography in 39 patients with histologically verified CS and in an age-adjusted random population sample (n = 124).. CS was inactive or responding to treatment in all patients. Concentrations of serum, LDL, and HDL cholesterol and serum triglycerides were similar in CS patients and in control subjects. Cholesterol absorption markers were higher in CS patients than in controls (eg serum campesterol to cholesterol ratio in CS 246 ± 18 vs in controls 190 ± 8 10(2) x μmol/mmol of cholesterol, p = 0.001). Cholesterol synthesis markers were lower in CS patients than in controls (eg serum lathosterol to cholesterol ratio in CS 102 ± 8 vs in controls 195 ± 5 10(2) x μmol/mmol of cholesterol, p = 0.000). In CS patients, cholesterol absorption markers significantly correlated with plasma prohormone brain natriuretic peptide (proBNP), a marker of hemodynamic load.. High cholesterol absorption efficiency, which is suggested to be atherogenic, characterized the metabolic profile of cholesterol in CS patients. The association between cholesterol absorption efficiency and plasma proBNP concentration, which suggests a link between inflammation, cholesterol homeostasis, and hemodynamic load, warrants further studies in order to confirm this finding and to reveal the underlying mechanisms.

Topics: Adult; Aged; Atherosclerosis; Body Mass Index; Cardiomyopathies; Case-Control Studies; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diet; Down-Regulation; Female; Finland; Heart Diseases; Hemodynamics; Homeostasis; Humans; Inflammation; Lipoproteins; Male; Middle Aged; Phytosterols; Risk Factors; Sarcoidosis; Sitosterols

β-Sitosterol, a common phytosterol, has been shown to exhibit anti-inflammatory effects. Here, we investigated the effect of β-sitosterol on high-fat diet (HFD) induced colitis in mice and on LPS-stimulated mouse intestinal macrophages.. C57BL/6J mice were maintained on an LFD (10 kcal% fat), an HFD (60 kcal% fat), or an HFD with β-sitosterol (20 mg/kg) administration for 8 weeks. The increased levels of body weight and epididymal fat pad weight as well as the concentrations of circulating proinflammatory cytokines and LPS in HFD mice compared with LFD mice were decreased by oral administration of β-sitosterol. The HFD-induced colonic inflammation evidenced by the increased expression of proinflammatory cytokines and the activation of nuclear factor kappa B (NF-κB) in the colon was also inhibited by β-sitosterol. In LPS-stimulated intestinal macrophages, β-sitosterol inhibited the production of proinflammatory cytokines and inflammatory enzymes as well as NF-κB activation. In addition, β-sitosterol significantly prevented the binding of LPS to intestinal as well as peritoneal macrophages. Furthermore, β-sitosterol potently inhibited the interaction between LPS and toll-like receptor 4 in intestinal macrophages transfected with control siRNA or MyD88 siRNA.. These findings indicate that β-sitosterol ameliorates HFD-induced colitis by inhibiting the binding of LPS to toll-like receptor 4 in the NF-κB pathway.

Topics: Animals; Colitis; Cytokines; Diet, High-Fat; Inflammation; Intestines; Lipopolysaccharides; Macrophages, Peritoneal; Male; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Myeloid Differentiation Factor 88; NF-kappa B; RNA, Small Interfering; Signal Transduction; Sitosterols; Toll-Like Receptor 4

The present study describes the tracheorelaxant and anti-inflammatory effects of Polygonatum verticillatum which may support its medicinal use in hyperactive airway complaints and inflammatory disorders.. The tracheorelaxant activity of crude extract of the rhizomes of P. verticillatum (PR) was assessed in isolated guinea-pig tracheal tissues immersed in tissue organ bath filled with Tyrode's solution and a continuous supply of carbogen gas (95% O2 and 5% CO2). The contractile and relaxant responses of the tissue were measured using isometric transducers coupled with Power-Lab data acquisition system. The anti-inflammatory effect was evaluated in carrageenan-induced rat paw edema model, while the lipoxygenase inhibitory activity was performed in the in-vitro assay. Various chromatographic and spectroscopic techniques were used for the isolation and characterization of pure molecules.. In isolated guinea-pig tracheal preparations, PR caused complete inhibition of the high K+ (80 mM) and carbachol-induced contractions however, it was more potent against K+ than CCh, similar to verapamil. Pretreatment of the tissue with PR, displaced the Ca2+ concentration-response curves to the right, similar to that induced by verapamil, indicating the presence of Ca2+ channel blocking like activity. When tested on carrageenan-induced rat paw edema, PR demonstrated a marked reduction in edema with 65.22% protection at 200 mg/kg, similar to aspirin. In the in-vitro assay, PR showed lipoxygenase inhibitory activity (IC50: 102 ± 0.19 μg/mL), similar to baicalein. Bioactivity-guided fractionation led to the isolation of 2-hydroxybenzoic acid and β-sitosterol.. These results indicate that the plant possesses tracheorelaxant, mediated possibly through a Ca2+ channel blockade mechanism, and anti-inflammatory activities, which may explain the medicinal use of this plant in airway disorders and inflammation.

Topics: Animals; Anti-Inflammatory Agents; Calcium Channel Blockers; Carbachol; Carrageenan; Edema; Female; Guinea Pigs; Inflammation; Male; Muscle Contraction; Muscle, Smooth; Phytotherapy; Plant Extracts; Polygonatum; Rats; Rats, Wistar; Respiratory Tract Diseases; Rhizome; Salicylic Acid; Sitosterols; Trachea; Verapamil

Evening Primrose oil is a natural product extracted by cold-pressed from Oenothera biennis L. seeds. The unsaponifiable matter of this oil is an important source of interesting minor compounds, like long-chain fatty alcohols, sterols and tocopherols. In the present study, sterols were isolated from the unsaponifiable matter of Evening Primrose oil, and the composition was identified and quantified by GC and GC-MS. The major components of sterols fraction were β-Sitosterol and campesterol. We investigated the ability of sterols from Evening Primrose oil to inhibit the release of different proinflammatory mediators in vitro by murine peritoneal macrophages stimulated with lipopolysaccharide. Sterols significantly and dose-dependently decreased nitric oxide production. Western blot analysis showed that nitric oxide reduction was a consequence of the inhibition of inducible nitric oxide synthetase expression. Sterols also reduced tumor necrosis factor-α, interleukine 1β and tromboxane B₂. However, sterols did not reduce prostaglandin E₂. The reduction of eicosanoid release was related to the inhibition of cyclooxygenase-2 expression. These results showed that sterols may have a protective effect on some mediators involved in inflammatory damage development, suggesting its potential value as a putative functional component of Evening Primrose oil.

Topics: Animals; Cholesterol; Cyclooxygenase 2 Inhibitors; Dose-Response Relationship, Drug; Inflammation; Inflammation Mediators; Lipopolysaccharides; Macrophages; Mice; Nitric Oxide; Nitric Oxide Synthase Type II; Oenothera biennis; Phytosterols; Phytotherapy; Plant Oils; Seeds; Sitosterols

In the present study, the efficacy of β-sitosterol isolated from an n-butanol extract of the seeds of the plant Moringa oleifera (Moringaceae) was examined against ovalbumin-induced airway inflammation in guinea pigs. All animals (except group I) were sensitized subcutaneously and challenged with aerosolized 0.5% ovalbumin. The test drugs, β-sitosterol (2.5mg/kg) or dexamethasone (2.5mg/kg), were administered to the animals (p.o.) prior to challenge with ovalbumin. During the experimental period (on days 18, 21, 24 and 29), a bronchoconstriction test (0.25% acetylcholine for 30s) was performed and lung function parameters (tidal volume and respiration rate) were measured for each animal. On day 30, blood and bronchoalveolar lavaged fluid were collected to assess cellular content, and serum was collected for cytokine assays. Lung tissue was utilized for a histamine assay and for histopathology. β-sitosterol significantly increased the tidal volume (V(t)) and decreased the respiration rate (f) of sensitized and challenged guinea pigs to the level of non-sensitized control guinea pigs and lowered both the total and differential cell counts, particularly eosinophils and neutrophils, in blood and bronchoalveolar lavaged fluid. Furthermore, β-sitosterol treatment suppressed the increase in cytokine levels (TNFα, IL-4 and IL-5), with the exception of IL-6, in serum and in bronchoalveolar lavaged fluid detected in model control animals. Moreover, treatment with β-sitosterol protected against airway inflammation in lung tissue histopathology. β-sitosterol possesses anti-asthmatic actions that might be mediated by inhibiting the cellular responses and subsequent release/synthesis of Th2 cytokines. This compound may have therapeutic potential in allergic asthma.

Topics: Acetylcholine; Animals; Anti-Asthmatic Agents; Asthma; Body Weight; Bronchial Spasm; Bronchoalveolar Lavage Fluid; Bronchoconstriction; Cell Count; Cytokines; Disease Models, Animal; Guinea Pigs; Histamine; Inflammation; Lung; Male; Ovalbumin; Respiratory System; Sitosterols; Th2 Cells

The objective of the present study was to examine the anti-inflammatory effects of β-sitosterol (SIT), the most common phytosterol in the diet, and to investigate its involvement in NF-κB and STAT1 pathways as potential mechanisms. In addition, the activity of the phosphatase SHP-1 as a negative modulator to these pathways, was investigated. Utilizing murine J774A.1 macrophages, cells were treated with various physiological concentrations of SIT and stimulated with LPS (100 ng/ml) for 6h. Results indicate that 1 and 16 μM SITs increased SHP-1 activity by 300% and 200%, respectively. Similar results were obtained using western blot analysis. Additionally, we observed reductions in the release of some pro-inflammatory cytokines and chemokines as well as an increase in anti-inflammatory IL-10 with SIT treatments. The results also demonstrate the inhibition of STAT1 with SIT treatment. Moreover, translocation of NF-κB to the nucleus was inhibited with SIT as indicated by decreased phosphorylation and the use of ImageStream cytometry. In conclusion, the present study demonstrates the anti-inflammatory effect on macrophages by inactivating STAT1 and NF-κB, which could be mediated by the activation of SHP-1.

Topics: Animals; Cells, Cultured; Chemokines; Cytokines; Down-Regulation; Inflammation; Interleukin-10; Lipopolysaccharides; Macrophages; Mice; NF-kappa B; Protein Tyrosine Phosphatase, Non-Receptor Type 6; Signal Transduction; Sitosterols; STAT1 Transcription Factor

This study was conducted to investigate the anti-inflammatory efficacy of Esenbeckia leiocarpa against the inflammation caused by the carrageenan using a murine air pouch model.. The effects of the crude hydroalcoholic extract (CHE), fractions (n-hexane (Hex) and ethyl acetate (AcOEt)), subfractions (polar (Pol) and nonpolar (Nonpol)), or isolated compounds (dihydrocorynantheol (DHC) and beta-sitosterol (β-Sit)) isolated from CHE upon leukocytes, exudate, myeloperoxidase (MPO) adenosine-deaminase (ADA), nitrate/nitrite (NO(x)), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and inhibitory kappa-B-alpha (IκB-α) degradation were evaluated. The CHE, Alk, Pol, Nonpol, DHC and β-Sit, inhibited leukocytes, exudate, MPO and ADA, NO(x), IL-1β, and TNF-α (P<0.05). The Hex and AcOEt fractions inhibited all of the proinflammatory parameters, except the exudate. The compound DHC prevented the IκB-α degradation.. E. leiocarpa possesses important anti-inflammatory properties. These inhibitory effects occurred along with the downregulation of nitric oxide, IL-1β and TNF-α levels. The isolated compounds DHC and β-Sit may be partially responsible for these anti-inflammatory effects.

Topics: Adenosine Deaminase; Alkaloids; Animals; Anti-Inflammatory Agents; Carrageenan; Cytokines; Down-Regulation; Inflammation; Leukocytes; Magnoliopsida; Mice; Plant Bark; Plant Extracts; Sitosterols; Treatment Outcome