Effect Of Beta-sitosterol Research Articles

Effects of beta-sitosterol on isolated human non-pregnant uterus in comparison to prostaglandin E2

Background: Beta-sitosterol (β-sitosterol) is one of the several phytosterols widely studied for its potential to reduce benign prostatic hyperplasia and blood cholesterol levels. Objective: In the present study, the effects of β-sitosterol on spontaneous and agonist-induced contractions in in vitro nonpregnant human uterus with respect to prostaglandin E2(PGE2) were investigated. Materials and Methods: Myometrial strips, measuring approximately 15 mm × 4 mm × 2 mm, were attained from hysterectomy samples of premenopausal women. Longitudinal muscle strips were mounted on tissue baths, under physiological conditions, to measure their isometric contraction. The effects of cumulative amounts of β-sitosterol on spontaneous motility in the absence and presence of prazosin, atropine, fulvestran, indomethacin, or ethylenediaminetetraacetic acid (EDTA), and on agonist-induced motor activity, were examined. Results: On strips in the follicular phase, both β-sitosterol (1–100 μg/ml) and PGE2(0.1–10 μg/ml) increase, in a concentration-dependent manner, muscular basic tonus and amplitude and frequency of spontaneous uterine contractions; whereas on strips obtained during periovulatory phase, β-sitosterol and PGE2cause inhibition of uterine motility. For contractile response, the effective concentrations (EC50) were 47.8 μg/ml and 5.19 μg/ml, respectively. Unlike indomethacin, the tissue pretreatment with prazosin, fulvestran, atropine, or ethylenediaminetetraacetic acid did not affect the contractile uterine responses to β-sitosterol. Furthermore, the β-sitosterol was able to potentiate the contractile response induced by acetylcholine and vasopressin. Conclusions: These observations suggest that β-sitosterol may be a useful modulator of the uterine motility during menstrual cycle, facilitating female fertility.

The effect of beta-sitosterol and its derivatives on depression by the modification of 5-HT, DA and GABA-ergic systems in mice.

Beta-sitosterol belongs to the group of phytosterols, which are active trace components existing in natural plants, known as the “key of life”, and have a steroid nucleus structure similar to cholesterol. Due to the insolubility issue of beta-sitosterol, most pharmacological studies and clinical applications are limited. Therefore, the modification of beta-sitosterol into its derivatives to enhance its pharmacologic activity is viable. In this study, 4 kinds of new beta-sitosterol derivative were obtained by an esterification reaction with beta-sitosterol, organic acids, EDCI and DMAP in dichloromethane. The chemical structures were defined by IR and NMR. Beta-sitosterol and its derivatives were used to carry out antidepressant research in the tail suspension test (TST) and the forced swimming test (FST) in mice. Additionally, the roles of different parts of the central nervous system (CNS) in the antidepressant-like effect of Sit-S, which is one of the beta-sitosterol derivatives, were also investigated. The results showed that the derivatives exhibited a stronger antidepressant activity than beta-sitosterol. Among the derivatives, administration of Sit-S (4 mg kg−1) gave the lowest immobility time in the TST, demonstrating that Sit-S exhibited the strongest antidepressant-like activity. The study into the roles of different parts of the CNS in the antidepressant-like effect of Sit-S showed that agomelatine (40 mg kg−1), haloperidol (0.2 mg kg−1) and bicuculline (4 mg kg−1) reversed the antidepressant effect of Sit-S (4 mg kg−1). This study confirmed the conclusions that beta-sitosterol derivatives broaden the pharmacological effects of beta-sitosterol, Sit-S (4 mg kg−1) exhibits antidepressant-like effects, and this antidepressant-like effect on male adult mice is mediated by the 5-HT, DA and GABA-ergic systems.

Abstract 849: Reactive oxygen species mediated activation of AMP activated protein kinase and c-Jun N-terminal kinase plays a critical role in beta sitosterol induced apoptosis in multiple myeloma U266 cells.

Abstract Although beta sitosterol has been well known to have anti-tumor activity in liver, lung, colon, stomach, breast and prostate cancers via cell cycle arrest and apoptosis induction, the underlying mechanism of anti-cancer effect of beta sitosterol in multiple myeloma cells was never elucidated until now. Thus, in the present study, the role of reactive oxygen species (ROS) in association with AMP-activated protein kinase (AMPK) and c-Jun N-terminal kinase (JNK) pathways was demonstrated in beta sitosterol treated multiple myeloma U266 cells. Beta sitosterol exerted cytotoxicity, increased sub-G1 apoptotic population and activated caspase-9 and -3, cleaved poly (ADP-ribose) polymerase (PARP) followed by decrease in mitochondrial potential in U266 cells. Beta sitosterol promoted ROS production, activated AMPK, acetyl-CoA carboxylase (ACC) and JNK in U266 cells. Also, beta sitosterol attenuated the phosphorylation of AKT, mammalian target of rapamycin (mTOR) and S6K, and the expression of cyclooxygenase (COX)2 and VEGF in U266 cells. Conversely, AMPK inhibitor compound C and JNK nhibitor SP600125 suppressed apoptosis induced by beta sitosterol in U266 cells. Furthermore, ROS scavenger N-acetyl-L-cysteine (NAC) attenuated beta sitosterol mediated sub-G1 accumulation, PARP cleavage, JNK and AMPK activation in U266 cells. Overall, these findings for the first time suggest that ROS mediated activation of cancer metabolism related genes such as AMPK and JNK plays an important role in beta sitosterol induced apoptosis in U266 multiple myeloma cells. Citation Format: Sun-Mi Cho, Ji-Sung Kim, Hyosook song, Eun-Jung Sohn, Ji-Hyun Kim, Ji Hoon Jung, Jung-Hyo Kim, Soo-Jin Jeong, Eun-OK Lee, HyoJeong Lee, Sung Hoon Kim. Reactive oxygen species mediated activation of AMP activated protein kinase and c-Jun N-terminal kinase plays a critical role in beta sitosterol induced apoptosis in multiple myeloma U266 cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 849. doi:10.1158/1538-7445.AM2013-849

β-Sitosterol activates Fas signaling in human breast cancer cells

beta-Sitosterol is the most abundant phytosterol. Phytosterols are enriched in legumes, oil seeds and unrefined plant oils as found in foods such as peanut butter, pistachios and sunflower seeds. beta-Sitosterol inhibits the growth of several specific types of tumor cells in vitro and decreases the size and the extent of tumor metastases in vivo. The effects of beta-sitosterol on the extrinsic apoptotic programmed cell death pathway in human breast MCF-7 and MDA-MB-231 adenocarcinoma cells were examined, along with the extent of its incorporation into cellular membranes and its effects on cell growth, expression of Fas receptor pathway proteins, and caspase-8 activity. The results show that beta-sitosterol exposure promotes its enrichment in transformed cell membranes and significantly inhibits tumor cell growth. Concurrently, Fas levels and caspase-8 activity are significantly increased. These actions are specific, as expression of other proteins of the Fas receptor pathway, including Fas ligand, FADD, p-FADD and caspase-8, remain unchanged. These findings support the hypothesis that beta-sitosterol is an effective apoptosis-promoting agent and that incorporation of more phytosterols in the diet may serve a preventive measure for breast cancer.

Effects of beta-sitosterol on microtubular systems in cervical cancer cells

To investigate beta-sitosterol's inhibitory effects on SiHa cells' growth, and the effects on microtubular system in SiHa cell. Proliferation inhibition of SiHa cell line was evaluated by MTT assay. Cell cycle of SiHa cells treated with beta-sitosterol was analyzed by flow cytometry. The expression and distribution of microtubule and microtubule associated protein 2 in SiHa cells were investigated by confocal microscopy. Immunoblotting analysis was used to determine tubulin alpha, microtubule associated protein 2, and the proportion of polymerization of tubulin. beta-sitosterol could obviously inhibit the proliferation of SiHa cells, and induce the accumulation of cells in S phase (rather than the G2/M phase) and mitotic arrest in the cell cycle. Confocal microscopy showed an abnormal microtubular network in SiHa cell treated with beta-sitosterol for 5 days, and the expression of microtubule associated protein 2 was marked down-regulated. Further analysis by immunoblotting confirmed the down-regulation of beta-sitosterol on the expression for both microtubule associated protein 2 and tubulin alpha. Moreover, beta-sitosterol reduced the proportion of polymerization of microtubule in a time-dependent manner. beta-sitosterol could down-regulate the expression of tubulin alpha and microtubule associated protein 2 in SiHa cells, and inhibit the microtubular polymerization. Our results suggested an anti-microtubule characteristic of beta-sitosterol which might contribute to the proliferation inhibition of SiHa cells.

Nasal insulin delivery in rabbits using soybean-derived sterylglucoside and sterol mixtures as novel enhancers in suspension dosage forms.

The effect of a soybean-derived sterol mixture (SS) and a steryl glucoside mixture (SG) as enhancers of the nasal absorption of insulin in rabbits was investigated. SS consists of beta-sitosterol (Sit), campesterol (Camp), stigmasterol (Stig) and brassicasterol (Bras), and SG is a mixture of their monoglucosides. For each component of SS tested for efficacy in promoting the systemic absorption of nasally administered insulin, the following order was observed: Sit> or =Camp>Stig. This finding was in agreement with the order of the enhancers' lipophilicity. In the case of SG, the effect of beta-sitosterol beta-D-glucoside (Sit-G) was significantly greater than that of SG. The pharmacological bioavailability was 6.7% for SG and 11.3% for Sit-G in the suspension dosage forms. SG showed a greater degree of enhancement of insulin permeation through the nasal mucosa than SS. To elucidate the contribution of SG to the enhanced absorption, insulin permeation through an artificial membrane and the nasal mucosa was investigated in vitro, and the results were compared with those for SS. The findings suggest that SG and SS have some effect on nasal mucosa lipids.

Sitosterin bei familiärer Hyperlipoproteinämie Typ II

The effect of beta-sitosterol on the lipid and lipoprotein level was evaluated in a randomised double-blind cross-over trial in 24 patients with primary familial type II hyperlipoproteinaemia over a period of 16 weeks. All patients completed the trial, however 10 of them had to be excluded from the evaluation due to fluctuations of their body weight or unreliable drug intake. Sitosterol lowered the total cholesterol level by 12.5% (P less than 0.01) from 9.96 mmol/l (3.69 g/l) to 8.37 mmol/l (3.23 g/l). The LDL-cholesterol level was lowered by 19.5% (P less than 0.05). The sitosterol concentration in plasma was consistently lower than 0.3% of total cholesterol. No side effects or tachyphylaxis was observed in the course of the trial. A return to normal of an increased serum cholesterol level by a combination of a lipid lowering diet and sitosterol monotherapy was only achieved in one patient.

The effect of beta-sitosterol on the metabolism of cholesterol and lipids in rats on a diet containing coconut oil.

1. Intraperitoneal injection of beta-sitosterol (5mg./rat/day for 25 days) into 1-year-old male Wistar rats fed on a low-fat diet supplemented with 10% of coconut oil resulted in a lowering of cholesterol and lipid concentrations in the tissues. 2. beta-Sitosterol increased the rate of biosynthesis of cholesterol and lipids in the tissues, but to an even greater extent enhanced their oxidative degradation. 3. The present results are similar to those previously obtained on a low-fat diet, indicating that the presence of fat had no marked effect on the action of beta-sitosterol.

Effect of beta-sitosterol on regression of hyperlipemia and increased plasma coagulability in the chicken.

Summary1. A cholesterol-induced hyperlipemia was fully counteracted (reduced to normal levels) by feeding beta-sitosterol.2. The decreased plasma clotting times associated with a hyperlipemia returned to control values when a normal lipid level was attained.3. An inverse relationship was demonstrated between plasma clotting time in presence of Russell's viper venom and degree of lipemia; i.e., a hyperlipemia resulted in decreased plasma clotting time, and vice versa. 4. Addition of 4% beta-sitosterol to the diet prevented or reversed an increased lipid and cholesterol concentration in liver and aorta.

Effect of beta-sitosterol on serum cholesterol concentration in the rat.

ß-Sitosterol added to a diet containing cholesterol alone or with cholic acid, diminished the accumulation of serum and liver cholesterol in the rat. This effect depended upon the quantity of ß-sitosterol added. Addition of ß-sitosterol to a diet containing corn oil enhanced the hypocholesteremic effect of corn oil. Calciferol and Q275 when fed to rats had no significant effect on serum cholesterol concentration, but calciferol caused an increase in the deposition of cholesterol in the liver.

Effect of Beta-Sitosterol on Regression of Hypercholesterosis and Atherosclerosis in Chickens.

Summary and Conclusions1. A previously elevated cholesterol concentration in the liver, serum, and aorta of the chicken was reduced by administration of beta-sitosterol in presence or absence of dietary cholesterol, or by withdrawal of dietary cholesterol. 2. Tissue cholesterol concentrations observed as a result of these treatments always approached the normal values. 3. When 4% beta-sitosterol was fed in the diet, total sterol content of liver was slightly lower than in birds fed the basal diet only. Further, total sterol content of the serum and aorta tended to be lower than that of birds fed basal diet only. 4. Atheroma regression in the chicken was accomplished by administration of beta-sitosterol in presence of dietary cholesterol. 5. Atheroma regression in the chicken was paralleled by a drop in cholesterol concentration of the blood and liver.

The effect of beta sitosterol on the serum lipids of young men with arteriosclerotic heart disease.

Previous studies in human beings on unrestricted diets have indicated that the plant sterols (beta or gamma sitosterol) cause decreases in serum cholesterol. In this study, 15 young men with previous myocardial infarction were given 12 to 18 Gm./day of beta sitosterol with resultant sustained reductions of serum cholesterol and beta lipoprotein lipid. Lipoprotein lipid fractionation was performed by paper electrophoresis. These changes occurred irrespective of initial serum cholesterol or content of diet. Control observations of the effects of diet, weight maintenance, and the inclusion of placebos brought about increased confidence that the changes were due to the administered sitosterol.

Effects of beta-sitosterol on regression of cholesterol atherosclerosis in rabbits.

Feeding β-sitosterol to atherosclerotic rabbits slightly increased the regression of plasma and liver cholesterol. However, β-sitosterol had no effect on aorta lipid, cholesterol or plaque regression.

Influence of esterification on hypocholesterolemic effect of beta sitosterol

Influence of esterification on hypocholesterolemic effect of beta sitosterol

The effect of beta-sitosterol upon intestinal absorption of cholesterol in the rat.

Thoracic duct lymph was collected from groups of rats fed varying doses of β-sitosterol concomitantly with cholesterol. The results indicated that β-sitosterol exerts only a slightly inhibiting effect upon intestinal absorption of cholesterol in the rat.