gamma-sitosterol and Disease-Models--Animal

This study investigated whether β-sitosterol has anti-allergic activity and explored its potential mechanism, using ovalbumin (OVA) allergic mouse model. Results indicated that supplementation with β-sitosterol at 5-20 mg kg

Topics: Animals; Disease Models, Animal; Food Hypersensitivity; Gastrointestinal Microbiome; Intestinal Mucosa; Mice; Mice, Inbred BALB C

Ocimum sanctum L. or Ocimum tenuiflorum L, commonly known as the Holy Basil in English or Tulsi in the various Indian languages, is a important medicinal plant in the various traditional and folk systems of medicine in Southeast Asia. Scientific studies have shown it to possess antiinflammatory, analgesic, antipyretic, antidiabetic, hepatoprotective, hypolipidemic, antistress, and immunomodulatory activities. Preclinical studies have also shown that Tulsi and some of its phytochemicals eugenol, rosmarinic acid, apigenin, myretenal, luteolin, β-sitosterol, and carnosic acid prevented chemical-induced skin, liver, oral, and lung cancers and to mediate these effects by increasing the antioxidant activity, altering the gene expressions, inducing apoptosis, and inhibiting angiogenesis and metastasis. The aqueous extract of Tulsi and its flavanoids, orintin, and vicenin are shown to protect mice against γ-radiation-induced sickness and mortality and to selectively protect the normal tissues against the tumoricidal effects of radiation. The other important phytochemicals like eugenol, rosmarinic acid, apigenin, and carnosic acid are also shown to prevent radiation-induced DNA damage. This review summarizes the results related to the chemopreventive and radioprotective properties of Tulsi and also emphasizes aspects that warrant future research to establish its activity and utility in cancer prevention and treatment.

Topics: Abietanes; Animals; Apigenin; Cinnamates; Depsides; Disease Models, Animal; Drug Evaluation, Preclinical; Eugenol; Humans; Luteolin; Neoplasms; Ocimum; Phytochemicals; Plant Extracts; Plants, Medicinal; Rosmarinic Acid; Sitosterols

The prevalence of duodenal ulceration in regions of developing countries with a stable diet is related to the staple food(s) in that diet. A higher prevalence occurs in areas where the diet is principally milled rice, refined wheat or maize, yams, cassava, sweet potato or green bananas, and a lower prevalence in areas where the staple diet is based on unrefined wheat or maize, soya, certain millets or certain pulses. Experiments using animal peptic ulcer models showed that the lipid fraction in foods from the staple diets of low prevalence areas gave protection against both gastric and duodenal ulceration, including ulceration due to non-steroidal anti-inflammatory drugs (NSAIDs), and also promoted healing of ulceration. The protective activity was found to lie in the phospholipid, sterol and sterol ester fractions of the lipid. Amongst individual phospholipids present in the phospholipid fraction, phosphatidyl ethanolamine (cephalin) and phosphatidyl choline (Lecithin) predominated. The sterol fraction showing activity contained β-sitosterol, stigmasterol and an unidentified isomer of β-sitosterol. The evidence shows that dietary phytosterols and phospholipids, both individually and in combination, have a protective effect on gastroduodenal mucosa. These findings may prove to be important in the prevention and management of duodenal and gastric ulceration including ulceration due to NSAIDs.

Topics: Animals; Diet; Disease Models, Animal; Duodenal Ulcer; Humans; Phospholipids; 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

Hepatocellular carcinoma (HCC) is highly refractory. β-Sitosterol has been reported to suppress proliferation and migration as well as interfere with cell metabolism in tumors. However, there is limited information on the effects of β-sitosterol on HCC. Herein, we used a xenograft mouse model to investigate the effects of β-sitosterol on HCC tumor growth. The molecular mechanism was elucidated using quantitative real-time PCR, western blotting, lentiviral transfection, CCK8, scratch, Transwell, and Ad-mCherry-GFP-LC3B assays. The results showed that HepG2 cells highly expressed complement C5a receptor 1. β-Sitosterol antagonized complement component 5a and exerted inhibitory effects on the proliferation and migration of HepG2 cells. The inhibitory effect of β-sitosterol was reversed by the knockdown of complement C5a receptor 1. Bioinformatics analysis suggested alpha fetoprotein (AFP) as a downstream factor of complement C5a receptor 1. β-Sitosterol inhibited AFP expression, which was reversed by complement C5a receptor 1 knockdown. The inhibitory effects of β-sitosterol on cell proliferation and migration were weakened by AFP overexpression. Furthermore, β-sitosterol induced autophagy in HepG2 cells, which was reversed by complement C5a receptor 1 knockdown and AFP overexpression. Blockade of autophagy by 3-MA attenuated β-sitosterol inhibition of proliferation and migration in HepG2 cells. Moreover, β-sitosterol inhibited HCC progression in vivo. Our findings demonstrate that β-sitosterol inhibits HCC advancement by activating autophagy through the complement C5a receptor 1/AFP axis. These findings recommend β-sitosterol as a promising therapy for HCC.

Topics: alpha-Fetoproteins; Animals; Autophagy; Carcinoma, Hepatocellular; Complement C5a; Disease Models, Animal; Humans; Liver Neoplasms; Mice

Sarcopenia refers to a decline in muscle mass and strength with age, causing significant impairment in the ability to carry out normal daily functions and increased risk of falls and fractures, eventually leading to loss of independence. Maintaining protein homeostasis is an important factor in preventing muscle loss, and the decrease in muscle mass is caused by an imbalance between anabolism and catabolism of muscle proteins. Although β-sitosterol has various effects such as anti-inflammatory, protective effect against nonalcoholic fatty liver disease (NAFLD), antioxidant, and antidiabetic activity, the mechanism of β-sitosterol effect on the catabolic pathway was not well known. β-sitosterol was assessed in vitro and in vivo using a dexamethasone-induced muscle atrophy mice model and C2C12 myoblasts. β-sitosterol protected mice from dexamethasone-induced muscle mass loss. The thickness of gastrocnemius muscle myofibers was increased in dexamethasone with the β-sitosterol treatment group (DS). Grip strength and creatine kinase (CK) activity were also recovered when β-sitosterol was treated. The muscle loss inhibitory efficacy of β-sitosterol in dexamethasone-induced muscle atrophy in C2C12 myotube was also verified in C2C12 myoblast. β-sitosterol also recovered the width of myotubes. The protein expression of muscle atrophy F-box (MAFbx) was increased in dexamethasone-treated animal models and C2C12 myoblast, but it was reduced when β-sitosterol was treated. MuRF1 also showed similar results to MAFbx in the mRNA level of C2C12 myotubes. In addition, in the gastrocnemius and tibialis anterior muscles of mouse models, Forkhead Box O1 (FoxO1) protein was increased in the dexamethasone-treated group (Dexa) compared with the control group and reduced in the DS group. Therefore, β-sitosterol would be a potential treatment agent for aging sarcopenia.

Topics: Animals; Dexamethasone; Disease Models, Animal; Forkhead Box Protein O1; Forkhead Transcription Factors; Mice; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Atrophy; Sarcopenia; Sitosterols; Ubiquitin-Protein Ligases

Plant sterols (PSs) cannot be synthesized in mammals and are exclusively diet-derived. PSs cross the blood-brain barrier and may have anti-neuroinflammatory effects. Obesity is linked to lower intestinal uptake and blood levels of PSs, but its effects in terms of neuroinflammation-if any-remain unknown. We investigated the effect of high-fat diet-induced obesity on PSs in the brain and the effects of the PSs campesterol and β-sitosterol on in vitro microglia activation. Sterols (cholesterol, precursors, PSs) and polyunsaturated fatty acid-derived lipid mediators were measured in the food, blood, liver and brain of C57BL/6J mice. Under a PSs-poor high-fat diet, PSs levels decreased in the blood, liver and brain (>50%). This effect was reversible after 2 weeks upon changing back to a chow diet. Inflammatory thromboxane B2 and prostaglandin D2 were inversely correlated to campesterol and β-sitosterol levels in all brain regions. PSs content was determined post mortem in human cortex samples as well. In vitro, PSs accumulate in lipid rafts isolated from SIM-A9 microglia cell membranes. In summary, PSs levels in the blood, liver and brain were associated directly with PSs food content and inversely with BMI. PSs dampen pro-inflammatory lipid mediators in the brain. The identification of PSs in the human cortex in comparable concentration ranges implies the relevance of our findings for humans.

Topics: Animal Feed; Animals; Cells, Cultured; Cholesterol; Chromatography, Liquid; Diet, High-Fat; Disease Models, Animal; Fatty Acids, Unsaturated; Humans; Lipidomics; Liver; Male; Mice; Mice, Inbred C57BL; Microglia; Neuroinflammatory Diseases; Obesity; Phytosterols; Sitosterols; Tandem Mass Spectrometry

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

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

Rheumatoid arthritis (RA) is a chronic disease with complex molecular network of pathophysiology, single drug is usually not full satisfactory because it is almost impossible to target the whole molecular network of the disease. Drug combinations that act synergistically with each another is an effective strategy in RA therapy. In this study, we aimed to establish a new strategy to search effective synergized compounds from Chinese herbal medicine (CHM) used in RA. Based on multi-information integrative approaches, imperatorin (IMP) and β-sitosterol (STO) were predicted as the most effective pair for RA therapy. Further animal experiments demonstrated that IMP+STO treatment ameliorated arthritis severity of collagen-induced arthritis (CIA) rats in a synergistic manner, whereas IMP or STO administration separately had no such effect. RNA sequencing and IPA analysis revealed that the synergistic mechanism of IMP+STO treatment was related to its regulatory effect on 5 canonical signaling pathways, which were not found when IMP or STO used alone. Moreover, LTA, CD83, and SREBF1 were 3 important targets for synergistic mechanism of IMP+STO treatment. The levels of these 3 genes were significantly up-regulated in IMP+STO group compared to model group, whereas IMP or STO administration separately had no effect on them. In conclusion, this study found that IMP and STO were 2 synergistic compounds from the CHM in RA therapy, whose synergistic mechanism was closely related to regulate the levels of LTA, CD83, and SREBF1.

Topics: Animals; Arthritis, Experimental; Arthritis, Rheumatoid; CD4-Positive T-Lymphocytes; Computational Biology; Disease Models, Animal; Drug Synergism; Drugs, Chinese Herbal; Furocoumarins; Male; Phytotherapy; Rats; Severity of Illness Index; Signal Transduction; Sitosterols

Liver disease associated with long-term drinking is one of the leading causes of death. There is an urgent need for more effective drugs to reduce alcoholic liver damage. Yin Chen Hao, a traditional Chinese herbal medicine, is widely used for liver diseases. Here, we aimed to explore the protective effect of β-sitosterol (the active ingredient of Artemisia spp.) on alcoholic liver injuries. We treated the rats with alcohol and different dosages of β-sitosterol to detect the expression levels of liver function indicators in serum. The functions of β-sitosterol were evaluated based on variations in histology, liver function indicators and DNA oxidative damages. The underlying mechanism was investigated by measuring lipid peroxidation, the antioxidant, the expression of cytochrome P450 2E1 and the expression of apoptosis related genes. The results showed that β-sitosterol could improve liver histology and suppress biochemical indicators caused by alcohol in serum. In addition, β-sitosterol alleviates alcohol-induced oxidative stress, such as restoring erythrocyte membrane fluidity, reducing glutathione depletion, restoring antioxidant enzyme activity and reducing malondialdehyde overproduction. Furthermore, β-sitosterol downregulated the expression of apoptosis-related genes through the PI3K/Akt pathway. In conclusion, β-sitosterol has a protective effect on chronic alcoholism and has broad clinical application prospects in the treatment of alcohol-induced liver damage.

Topics: Alcohol Drinking; Animals; Antioxidants; Apoptosis; Apoptosis Regulatory Proteins; Disease Models, Animal; DNA Damage; Lipid Peroxidation; Liver; Liver Diseases, Alcoholic; Male; Oxidative Stress; Phosphatidylinositol 3-Kinase; Proto-Oncogene Proteins c-akt; Rats, Wistar; Sitosterols

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

To study the effects of stigmasterol and β-sitosterol on high-fat Western diet (HFWD)-induced nonalcoholic fatty liver disease (NAFLD), lipidomic analyses were conducted in liver samples collected after 33 weeks of the treatment. Principal component analysis showed these phytosterols were effective in protecting against HFWD-induced NAFLD. Orthogonal projections to latent structures-discriminate analysis (OPLS-DA) and S-plots showed that triacylglycerols (TGs), phosphatidylcholines, cholesteryl esters, diacylglycerols, and free fatty acids (FFAs) were the major lipid species contributing to these discriminations. The alleviation of NAFLD is mainly associated with decreases in hepatic cholesterol, TGs with polyunsaturated fatty acids, and alterations of free hepatic FFA. In conclusion, phytosterols, at a dose comparable to that suggested for humans by the FDA for the reduction of plasma cholesterol levels, are shown to protect against NAFLD in this long-term (33-week) study.

Topics: Animals; Cholesterol; Diet, High-Fat; Disease Models, Animal; Humans; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Sitosterols; Stigmasterol; Triglycerides

To investigate and compare the effects of two common dietary phytosterols, stigmasterol and β-sitosterol, in altering lipid metabolism and attenuating nonalcoholic fatty liver disease (NAFLD).. Stigmasterol and β-sitosterol were administered to mice at 0.4% in a high-fat western-style diet (HFWD) for 17 weeks.. Stigmasterol and β-sitosterol significantly ameliorated HFWD-induced fatty liver and metabolic abnormalities, including elevated levels of hepatic total lipids, triacylglycerols, cholesterol and liver histopathology. Both phytosterols decreased the levels of intestinal bile acids, accompanied by markedly increased fecal lipid levels. In addition, they altered the expression of genes involved in lipid metabolism. β-Sitosterol was less effective in affecting most of these parameters. Lipidomic analysis of liver and serum samples showed that stigmasterol prevented the HFWD-induced elevation of some di- and triacylglycerol species and lowering of some phospholipid species. Stigmasterol also decreased serum levels of ceramides.. Stigmasterol and β-sitosterol, at a dose corresponding to that suggested for humans by the FDA for lowering cholesterol levels, are shown to alleviate HFWD-induced NAFLD. Stigmasterol was more effective than β-sitosterol, possibly because of its suppression of hepatic lipogenic gene expression and modulation of circulating ceramide levels.

Topics: Animals; Bile Acids and Salts; Ceramides; Diet, High-Fat; Disease Models, Animal; Feces; Lipid Metabolism; Mice; Non-alcoholic Fatty Liver Disease; Phospholipids; Sitosterols; Stigmasterol; Treatment Outcome; Triglycerides

Dry citrus peel (Chenpi) is not only consumed as a dietary supplement, but also used for the treatment of respiratory diseases. Pinelliae Rhizoma Praeparatum (Banxia) is always used with Chenpi for the treatment of respiratory diseases, but β-sitosterol, the main active component in Banxia, as a food additive, shows no respiratory system activity. In the present study, the pharmacokinetic characters showed that the absorption of the active components of Chenpi was accelerated under pathological conditions combined with Banxia. Although the bioavailability of active components did not significantly change, the distribution of active components in tissues increased, particularly in the target organ. These results are consistent with the combination of Chenpi with β-sitosterol. Furthermore, the pharmacodynamics result also indicated that Chenpi combined with Banxia or β-sitosterol was able to ameliorate histopathologic damage and decrease the levels of inflammatory factors. The results suggest that pharmacokinetic interactions improve the pharmacological activity of Chenpi in respiratory diseases.

Topics: Acute Lung Injury; Animals; Citrus; Disease Models, Animal; Drugs, Chinese Herbal; Fruit; Lipopolysaccharides; Male; Pinellia; Plant Extracts; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Sitosterols

Inhibitors of thrombin, a key enzyme in the blood coagulation cascade, are of great interest because of their selective specificity and effectiveness in anticoagulation therapy against cardiovascular disorders. The natural soybean phytosterol, β-sitosterol (BSS) demonstrated anticoagulant activity by dose-dependent inhibition of thrombin in an uncompetitive manner with a K

Topics: Animals; Anticoagulants; Antithrombins; Catalysis; Disease Models, Animal; Female; Fibrinogen; Humans; Male; Mice; Plants; Platelet Aggregation Inhibitors; Sitosterols; Thrombin; Thrombosis

Hair loss (alopecia) is a universal problem for numerous people in the world. The present study was conducted to investigate the effects of red ginseng oil (RGO) and its major components on hair re-growth using testosterone (TES)-induced delay of anagen entry in C57BL/6 mice and their mechanisms of action. Seven-week-old C57BL/6 mice were daily treated with TES for 1 h prior to topical application of 10% RGO, 1% linoleic acid (LA), 1% β-sitosterol (SITOS), or 1% bicyclo(10.1.0)tridec-1-ene (BICYCLO) once a day for 28 days. Hair regenerative capacity was significantly restored by treatment of RGO and its major compounds in the TES-treated mice. Histological analysis showed that RGO along with LA and SITOS but not BICYCLO promoted hair growth through early inducing anagen phase that was delayed by TES in mice. Treatment of mice with RGO, LA, or SITOS up-regulated Wnt/β-catenin and Shh/Gli pathways-mediated expression of genes such as β-catenin, Lef-1, Sonic hedgehog, Smoothened, Gli-1, Cyclin D1, and Cyclin E in the TES-treated mice. In addition, RGO and its major components reduced the protein level of TGF-β but enhanced the expression of anti-apoptotic protein Bcl-2. These results suggest that RGO is a potent novel therapeutic natural product for treatment of androgenic alopecia possibly through hair re-growth activity of its major components such as LA and SITOS.

Topics: Alopecia; Animals; beta Catenin; Cyclins; Disease Models, Animal; Gene Expression Regulation; Hair Follicle; Hedgehog Proteins; Linoleic Acid; Lymphoid Enhancer-Binding Factor 1; Male; Mice; Mice, Inbred C57BL; Panax; Plant Oils; Proto-Oncogene Proteins c-bcl-2; Regeneration; Sitosterols; Smoothened Receptor; Testosterone; Transforming Growth Factor beta; Zinc Finger Protein GLI1

The hexanic, ethyl acetate and methanolic extracts from branches of Stenocereus stellatus were tested in both the 12-O-tetradecanoylphorbol-13-acetate (TPA) - induced ear oedema model and antimicrobial activity assay. The % of oedema inhibition, the Minimum Inhibitory Concentration (MIC), as well as the polyphenolic and flavonoid content were determined. Also, extracts were analysed by gas chromatography-mass spectrometry (GC-MS). In TPA model, the three extracts showed moderate oedema inhibition. In the antimicrobial activity assay, methanolic extract shows better MIC against all strains. The lowest MICs were for Candida albicans (31 μg/mL) and Rhizopus sp. (15 μg/mL). Also, 50.78 mg eq. of gallic acid/g extract of polyphenol and 115.12 mg eq. of catequine/g extract of flavonoids content were founded in ethyl acetate extract. In the chromatographic analysis, β-sitosterol, β-amyrine, betulin and some other molecules were identified. The results show that S. stellatus possess antimicrobial activities against some fungus species.

Topics: Animals; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Cactaceae; Candida albicans; Disease Models, Animal; Edema; Flavonoids; Gas Chromatography-Mass Spectrometry; Male; Microbial Sensitivity Tests; Phorbol Esters; Plant Extracts; Polyphenols; Rhizopus; Secondary Metabolism; Sitosterols

Benign prostatic hyperplasia (BPH) is a common urological disorder of men. The ethnomedicinal use of an African plant Prunus africana (Hook.f.) Kalkman (Pygeum) in treating men's problems made it a popular remedy all over the globe for the treatment of BPH and related disorders. However, rampant collections made from the wild in Africa have pushed the plant to Appendix II of CITES demanding conservation of the species.. In the present study, the aim was to unearth the protective effect of bark of different species of Prunus against BPH. The five selected Indian plants of family Rosaceae viz. Prunus amygdalus Stokes, Prunus armeniaca L., Prunus cerasoides Buch.-Ham. ex D. Don, Prunus domestica L. and Prunus persica (L.) Batsch were evaluated against P. africana (Hook.f.) Kalkman for a suitable comparison of efficacy as antiBPH agents.. The antiBPH activity was evaluated in testosterone (2mg/kg/day, s.c, 21 days) induced BPH in Wistar rats. The parameters studied were body weights; histopathological examination, immunohistochemistry (PCNA) and biochemical estimations of the prostate; supported by prostatic index, testicular index, creatinine, testosterone levels; antioxidant and anti-inflammatory evaluation. The study also included chemical profiling using three markers (β-sitosterol, docosyl ferulate and ursolic acid) and estimation of β-sitosterol content through GC.. The Prunus species showed the presence of all the three markers in their TLC fingerprint profile and maximum amount of β-sitosterol by GC was observed in P. domestica. Interestingly, all the species exhibited significant amelioration in testosterone induced parameters with P. domestica showing the most encouraging effect as indicated from histopathological examination, immunohistochemistry and biochemical studies. The Prunus species further showed remarkable anti-inflammatory and antioxidant activity signifying their role in interfering with various possible factors involved in BPH.. These findings are suggestive of a meaningful inhibitory effect of testosterone induced BPH by the bark of different species of Prunus in the order of P. domestica, P. persica, P. amygdalus, P. cerasoides and P. armeniaca with an efficacy of P. domestica comparable to P. africana and can be used as the potential backup of Pygeum for the management of BPH.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Biomarkers; Chromatography, Gas; Chromatography, Thin Layer; Disease Models, Animal; Inflammation Mediators; Male; Oxidative Stress; Phytotherapy; Plant Bark; Plant Extracts; Plants, Medicinal; Prostate; Prostatic Hyperplasia; Prunus armeniaca; Prunus domestica; Prunus dulcis; Prunus persica; Rats, Wistar; Sitosterols; Testosterone; Triterpenes; Urological Agents; Ursolic Acid

The aim of our study was to investigate vascular effects of oxysterols and oxyphytosterols on reactive oxygen species (ROS), endothelial progenitor cells, endothelial function and atherogenesis.. Male apoE-/-mice were treated with cholesterol, sitosterol, 7-ß-OH-cholesterol, 7-ß-OH-sitosterol, or cyclodextrin by daily intraperitoneal application. The respective concentrations in the plasma and in the arterial wall were determined by gas chromatography-flame ionization or mass spectrometry. ROS production was assessed by electron-spin resonance spectroscopy in the aorta, endothelial function of aortic rings and atherosclerosis in the aortic sinus was quantitated after 4 weeks.. Compared to vehicle, there was no difference in plasma cholesterol levels and arterial wall concentrations after i.p. application of cholesterol. 7-ß-OH-cholesterol concentrations were increased in the plasma (33.7±31.5 vs. 574.57.2±244.92 ng/ml) but not in the arterial wall (60.1±60.1 vs. 59.3±18.2 ng/mg). Sitosterol (3.39±0.96 vs. 8.16±4.11 mg/dL; 0.08±0.04 vs. 0.16±0.07 μg/mg, respectively) and 7-ß-OH-sitosterol concentrations (405.1±151.8 vs. 7497±3223 ng/ml; 0.24±0.13 vs. 16.82±11.58 ng/mg, respectively) increased in the plasma and in the aorta. The i.p-application of the non-oxidized cholesterol or sitosterol did not induce an increase of plasma oxysterols or oxyphytosterols concentrations. Oxidative stress in the aorta was increased in 7-ß-OH-sitosterol treated mice, but not in mice treated with cholesterol, sitosterol, or 7-ß-OH-cholesterol. Moreover, cholesterol, sitosterol, 7-ß-OH-cholesterol, and 7-ß-OH-sitosterol did not affect endothelial-dependent vasodilation, or early atherosclerosis.. Increased oxyphytosterol concentrations in plasma and arterial wall were associated with increased ROS production in aortic tissue, but did not affect endothelial progenitor cells, endothelial function, or early atherosclerosis.

Topics: Animals; Aorta; Aortic Diseases; Apolipoproteins E; Atherosclerosis; Cell Movement; Cells, Cultured; Cholesterol; Cyclodextrins; Disease Models, Animal; Endothelial Progenitor Cells; Hydroxycholesterols; Male; Mice, Inbred C57BL; Mice, Knockout; Oxidative Stress; Reactive Oxygen Species; Sitosterols; Time Factors; Vasodilation

In Mexico Agave angustifolia has traditionally been used to treat inflammation. The aim of this study was to measure the anti-inflammatory effect of the extract of A. angustifolia, the isolation and identification of active compounds. From the acetone extract two active fractions were obtained, (AsF13 and AaF16). For the characterization of pharmacological activity, the acute inflammatory model of mouse ear edema induced with TPA was used. The tissue exposed to TPA and treatments were subjected to two analysis, cytokine quantification (IL-1β, IL-6, IL-10 and TNF-α) and histopathological evaluation. The active fraction (AaF16) consisted principally of 3-O-[(6'-O-palmitoyl)-β-D-glucopyranpsyl] sitosterol. In AaF13 fraction was identified β-sitosteryl glucoside (2) and stigmasterol (3). The three treatments tested showed a concentration-dependent anti-inflammatory effect (AaAc Emax = 33.10%, EC50 = 0.126 mg/ear; AaF13 Emax = 54.22%, EC50 = 0.0524 mg/ear; AaF16 Emax = 61.01%, EC50 = 0.050 mg/ear). The application of TPA caused a significant increase on level of IL-1β, IL-6 and TNFα compared with basal condition, which was countered by any of the experimental treatments. Moreover, the experimental treatments induced a significant increase in the levels of IL-4 and IL-10, compared to the level observed when stimulated with TPA. Therefore, the anti-inflammatory effect of Agave angustifolia, is associated with the presence of 3-O-[(6'-O-palmitoyl)-β-D-glucopyranosyl] sitosterol.

Topics: Agave; Animals; Anti-Inflammatory Agents; Cytokines; Disease Models, Animal; Ear; Edema; Male; Mice; Plant Extracts; Sitosterols

Obesity is associated with increased systemic and airway oxidative stress, which may result from a combination of adipokine imbalance and antioxidant defenses reduction. Obesity-mediated oxidative stress plays an important role in the pathogenesis of dyslipidemia, vascular disease, and nonalcoholic hepatic steatosis. The antidyslipidemic activity of pigeon pea were evaluated by high-fat diet (HFD) hamsters model, in which the level of high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC), and total triglyceride (TG) were examined. We found that pigeon pea administration promoted cholesterol converting to bile acid in HFD-induced hamsters, thereby exerting hypolipidemic activity. In the statistical results, pigeon pea significantly increased hepatic carnitine palmitoyltransferase-1 (CPT-1), LDL receptor, and cholesterol 7α-hydroxylase (also known as cytochrome P450 7A1, CYP7A1) expression to attenuate dyslipidemia in HFD-fed hamsters; and markedly elevated antioxidant enzymes in the liver of HFD-induced hamsters, further alleviating lipid peroxidation. These effects may attribute to pigeon pea contained large of unsaturated fatty acids (UFA; C18:2) and phytosterol (β-sitosterol, campesterol, and stigmasterol). Moreover, the effects of pigeon pea on dyslipidemia were greater than β-sitosterol administration (4%), suggesting that phytosterone in pigeon pea could prevent metabolic syndrome.

Topics: Animals; Antioxidants; Cajanus; Carnitine O-Palmitoyltransferase; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Cholesterol, HDL; Cholesterol, LDL; Chromatography, High Pressure Liquid; Cricetinae; Diet, High-Fat; Disease Models, Animal; Hypercholesterolemia; Lipid Peroxidation; Liver; Male; Obesity; Oxidative Stress; Phytosterols; Receptors, LDL; Sitosterols; Stigmasterol; Triglycerides

To select the optimal combination of five active component of Banxia Xiexin Decoction on gastric ulcer rat, and observe its effect on Leptin and ET-1.. Eighty-seven SD rats were randomly divided into normal group, sham-operated group and acetic acid-induced gastric ulcer group, omeprazole group as a positive control, five active components (glycyrrhetic acid, beta-sitosterol, berberine, baicalin and ginsenoside) of Banxia Xiexin Decoction were divided into groups by L16 orthogonal design. The ulcer area, and the content of Leptin and ET-1, and the mRNA expression level of both were detected.. Among the sixteen orthogonal design groups, the ulcer area of these groups using both beta-sitosterol and berberine was the smallest (P < 0.05), the content of Leptin of these groups using both glycyrrhetic acid and ginsenoside was the highest in blood serum (P < 0.05), the group using glycyrrhetic acid had the minimum concentration of ET-1 in blood plasma. Compared with model group, berberine could raise the mRNA expression level of Leptin (P < 0.01), and beta-sitosterol could lower the mRNA expression level of ET-1 (P < 0.01).. The pathogenesis of gastric ulcer may be related with the down-regulation of concentration and mRNA expression level of Leptin, and upregulation of concentration and mRNA expression level of ET-1, the active components in Banxia Xiexin Decoction may upregulated Leptin and inhibit ET-1 to accelerate the healing of gastric ulcer.

Topics: Acetates; Animals; Berberine; Disease Models, Animal; Drugs, Chinese Herbal; Endothelin-1; Flavonoids; Gastric Mucosa; Leptin; Male; Plants, Medicinal; Random Allocation; Rats; Rats, Sprague-Dawley; RNA, Messenger; Sitosterols; Stomach Ulcer

Alopecia is a psychologically distressing phenomenon. Androgenetic alopecia (AGA) is the most common form of alopecia, which affects millions of men and women worldwide, and is an androgen driven disorder. To study the effect of β-sitosterol phyto-vesicles on AGA, the testosterone-induced alopecia model was used. For the study, the albino rats were used and the period of study was 21 days. β-Sitosterol is a phytosterol which is chemically similar to cholesterol. This compound was found suitable for the preparation of phyto-vesicles by the process involving its complexation with phosphatidyl choline. Pharmacokinetic studies of β-sitosterol reveal its poor absorption through the intestine. The objective of the present study is to enhance the bioavailability of β-sitosterol by its complexation with phosphatidyl choline and then to formulate it as phyto-vesicles for the treatment of alopecia. The complex of β-sitosterol was prepared with phosphatidyl choline and characterized on the basis of solubility, melting point, TLC, UV, IR and NMR spectroscopy. This complex was then formulated as phyto-vesicles and then characterized. The results revealed that effect on alopecia is better in case of phyto-vesicles as compared to the complex, physical mixture and the β-sitosterol itself. Enhanced bioavailability of the β-sitosterol complex may be due to the amphiphilic nature of the complex, which greatly enhance the water and lipid solubility of the compound. The present study clearly indicates the superiority of phyto-vesicles over the complex and β-sitosterol, in terms of better absorption and improved activity for the treatment of alopecia.

Topics: Absorption; Alopecia; Animals; Biological Availability; Disease Models, Animal; Drug Delivery Systems; Humans; Intestines; Male; Phosphatidylcholines; Rats; Rats, Wistar; Sitosterols; Solubility; Testosterone

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 roots of Cyathula officinalis Kuan are widely used in Chinese medicine for the treatment of inflammatory disorders. Here, the ability of C. officinalis Kuan to downregulate matrix metalloproteinase (MMP)-13 was examined since MMP-13 is an important enzyme for the degradation of the cartilage collagen matrix, especially under arthritic conditions. The ethanol extract of C. officinalis Kuan as well as the N-hexane and chloroform soluble fractions were found to potently inhibit MMP-13 induction in IL-1 β-treated SW1353 cells, a human chondrosarcoma cell line, at 50-200 µg/mL. Activity-guided separation led to the isolation of six compounds, palmitic acid (1), β-sitosterol (2), α-spinasterol (3), atractylenolide I (4), 1,3-diacetoxy-tetradeca-6E,12E-dien-8,10-dyn (5), and N-trans-feruloyl-3-methyldopamine (6). Among these, 4 and 5 exhibited MMP-13 downregulating activity in IL-1 β-treated SW1353 cells. And 4 also showed anti-oedematous activity against λ-carageenan-induced paw edema in mice at 20-200 mg/kg, p. o. The results of this study provide information that can help elucidate the action mechanism of C. officinalis Kuan. In addition, the results presented here suggest that C. officinalis Kuan and its constituents may have the potential for chondroprotection against cartilage degrading disorders.

Topics: Acetates; Alkynes; Amaranthaceae; Animals; Carrageenan; Cartilage; Cell Line, Tumor; Chondrocytes; Chondrosarcoma; Disease Models, Animal; Dopamine; Down-Regulation; Edema; Humans; Hypolipidemic Agents; Interleukin-1beta; Lactones; Male; Matrix Metalloproteinase 13; Medicine, Chinese Traditional; Mice; Mice, Inbred ICR; Phytotherapy; Plant Extracts; Plant Roots; Sesquiterpenes; Sitosterols; Stigmasterol

In traditional Indian medicinal treatise there are several Ayurvedic formulations mentioned which have been claimed as potential wound healing agents like Madhu Ghrita and Jatyadi Taila. Jatyadi Taila (JT) is a medicated oil formulation (Taila) popularly used in the treatment of various topical wounds.. Though JT has its composition recorded in ancient Ayurvedic texts, there have been minimal attempts to standardize its use in the management of wound. The current work evaluates the wound healing efficacy of JT and also provides evidence of the dermal absorption kinetics of Karanjin from JT.. JT was subjected to preliminary phytochemical evaluation. Therapeutically active marker components β-sitosterol, lupeol and karanjin were detected and separated using HPTLC. As a part of safety evaluation, skin irritation potential of JT was evaluated on rabbit skin. Excision wound model in rats were used to evaluate the wound healing efficacy of JT. Histopathological and biochemical evaluations of excised skin tissues at wound sites were carried out. The HPTLC method developed was also validated to evaluate the pharmacokinetics of Karanjin from JT after topical application on pinna of rabbit.. Preliminary phytochemical evaluation of JT revealed presence of flavonoids, essential oils, tannins, glycosides, steroids and alkaloids while resins were found to be absent. HPTLC confirmed the presence of karanjin, lupeol and β-sitosterol in JT. JT was found to be non-irritant when applied to the skin of rabbits. Topical application of JT on excision wounds caused significantly faster reduction in wound area as compared to the application of modern topical formulation (Neosporin(®)) and untreated control wounds. Animals treated with JT showed significant increase in protein, hydroxyproline and hexosamine content in the granulation tissue when compared with the untreated controls. Wound healing potential of JT was found to be dose dependant. HPTLC method was successfully used to evaluate the pharmacokinetics of Karanjin after topical application of JT on rabbit pinna.. Current work demonstrates a modern approach towards standardization of the use of traditional topical formulation JT. The results justify the traditional claim of JT for its use in the management of wounds.

Topics: Administration, Topical; Amines; Animals; Bacitracin; Benzopyrans; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Combinations; Female; Granulation Tissue; Hydroxyproline; Male; Medicine, Ayurvedic; Neomycin; Pentacyclic Triterpenes; Phytotherapy; Plant Extracts; Polymyxin B; Proteins; Rabbits; Rats; Rats, Wistar; Sitosterols; Skin; Wound Healing; Wounds and Injuries

Asclepias curassavica Linn. is a traditional medicinal plant used by tribal people in the western ghats, India, to treat piles, gonorrhoea, roundworm infestation and abdominal tumours. We have determined the protective effect of beta-sitosterol isolated from A. curassavica in colon cancer, using in vitro and in vivo models.. The active molecule was isolated, based upon bioassay guided fractionation, and identified as beta-sitosterol on spectral evidence. The ability to induce apoptosis was determined by its in vitro antiradical activity, cytotoxic studies using human colon adenocarcinoma and normal monkey kidney cell lines, and the expression of beta-catenin and proliferating cell nuclear antigen (PCNA) in human colon cancer cell lines (COLO 320 DM). The chemopreventive potential of beta-sitosterol in colon carcinogenesis was assessed by injecting 1,2-dimethylhydrazine (DMH, 20 mg/kg b.w.) into male Wistar rats and supplementing this with beta-sitosterol throughout the experimental period of 16 weeks at 5, 10, and 20 mg/kg b.w.. beta-sitosterol induced significant dose-dependent growth inhibition of COLO 320 DM cells (IC50 266.2 microM), induced apoptosis by scavenging reactive oxygen species, and suppressed the expression of beta-catenin and PCNA antigens in human colon cancer cells. beta-sitosterol supplementation reduced the number of aberrant crypt and crypt multiplicity in DMH-initiated rats in a dose-dependent manner with no toxic effects.. We found doses of 10-20 mg/kg b.w. beta-sitosterol to be effective for future in vivo studies. beta-sitosterol had chemopreventive potential by virtue of its radical quenching ability in vitro, with minimal toxicity to normal cells. It also attenuated beta-catenin and PCNA expression, making it a potential anticancer drug for colon carcinogenesis.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents, Phytogenic; Antioxidants; Apoptosis; Asclepias; beta Catenin; Cell Line; Cell Line, Tumor; Colon; Colonic Neoplasms; Disease Models, Animal; Dose-Response Relationship, Drug; Haplorhini; Humans; Kidney; Male; Phytotherapy; Plant Extracts; Proliferating Cell Nuclear Antigen; Rats; Rats, Wistar; Sitosterols

We have produced a chloroform extract from Achillea which includes stigmasterol and sitosterol. By comparing it with the pure compounds an anti-inflammatory effect (with mouse ears) is assumed. The topical anti-inflammatory effect of the chloroform extract from Achillea ageratum (Asteraceae) and of stigmasterol and beta-sitosterol, isolated of this extract has been evaluated, against to 12-0-tetradecanoylphorbol acetate (TPA)-induced mouse ear edema, using simple (acute model) and multiple applications (chronic model) of the phlogistic agent. Myeloperoxydase activity also was studied in the inflamed ears. In the acute model the extract exerted a dose-dependent effect. All the doses assayed (1, 3 and 5 mg/ear) significantly reduced the edema (50%, 66% and 82%, respectively). The isolated sterols stigmasterol and beta-sitosterol (with doses of 0.5 mg/ear) had similar effect as the extract with doses of 1 and 3 mg (59% and 65% respectively). In the chronic model the anti-inflammatory effect generally was a more moderate one. The highest dose of the extract decreased the edema reduction to 26% with the highest dose of the extract applied. With the compounds the effect decreased to 36% with stigmasterol, and 40.6% with beta-sitosterol. Myeloperoxydase activity (MPO) was reduced by the extract and the compounds in the acute model, however, in the chronic edema, the enzyme inhibition was very weak with all treatments even with the standard substance. These results indicate that the chloroform extract of Achillea ageratum and some of the its components stigmasterol and beta-sitosterol are more effective as topical anti-inflammatory agents in acute than in the chronic process and their action is markedly influenced by the inhibition of neutrophil migration into inflamed tissue.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents; Chloroform; Chronic Disease; Dexamethasone; Disease Models, Animal; Ear; Edema; Indomethacin; Mice; Peroxidase; Plant Extracts; Plants, Medicinal; Sitosterols; Stigmasterol; Tetradecanoylphorbol Acetate

Attempts were made to develop an animal model for phytosterolemia. Infusion of Intralipid containing 0.2% sitosterol in rats gave circulating levels of sitosterol of about 2.5 mmol/l, which is similar to or higher than those present in patients with untreated phytosterolemia. In addition, the infusions gave serum levels of cholesterol nearly twice those obtained in rats infused with Intralipid alone or Intralipid containing 0.2% cholesterol. The hepatic HMG-CoA reductase activity was unaffected or slightly increased by the sitosterol infusions (not statistically significant). The cholesterol 7 alpha-hydroxylase activity was slightly depressed (ca. 30%). In the case of 7 alpha-hydroxylation of endogenous cholesterol, the depression reached statistical significance (p less than 0.05). The microsomal content of sitosterol in the sitosterol-infused rats was about 30% of that of microsomal cholesterol. The effect of sitosterol on 7 alpha-hydroxylation of cholesterol was investigated by incubations of acetone powder of rat liver microsomes with mixtures of cholesterol and sitosterol. Sitosterol mixed with cholesterol to a composition similar to that found in the above microsomal fraction had a depressing effect on 7 alpha-hydroxylation of cholesterol. This degree of depression was of the same magnitude as that found in the sitosterol infusion experiments. The possibility is discussed that the hypercholesterolemia obtained in the beta-sitosterol-infused rats is due to the inhibitory effect of sitosterol on the cholesterol 7 alpha-hydroxylase.

Topics: Animals; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Disease Models, Animal; Hydroxymethylglutaryl CoA Reductases; Hypercholesterolemia; Male; Microsomes, Liver; Phytosterols; Rats; Rats, Inbred Strains; Sitosterols; Steroid Hydroxylases