phytoestrogens and gamma-sitosterol

All the currently available cancer therapeutic options are expensive but none of them are safe. However, traditional plant-derived medicines or compounds are relatively safe. One widely known such compound is beta-sitosterol (BS), a plant derived nutrient with anticancer properties against breast cancer, prostate cancer, colon cancer, lung cancer, stomach cancer, ovarian cancer, and leukemia. Studies have shown that BS interfere with multiple cell signaling pathways, including cell cycle, apoptosis, proliferation, survival, invasion, angiogenesis, metastasis and inflammation. Most of the studies are incomplete partly due to the fact that BS is relatively less potent. But the fact that it is generally considered as nontoxic, the opposite of all currently available cancer chemo-therapeutics, is missed by almost all research communities. To offset the lower efficacy of BS, designing BS delivery for "cancer cell specific" therapy hold huge potential. Delivery of BS through liposome is one of such demonstrations that has shown to be highly promising. But further research did not progress neither in the field of drug delivery of BS nor in the field on how BS mediated anticancer activities could be improved, thus making BS an orphan nutraceutical. Therefore, extensive research with BS as potent anticancer nutraceutical is highly recommended.

Topics: Apoptosis; Breast Neoplasms; Cell Cycle; Colonic Neoplasms; Dietary Supplements; Drug Delivery Systems; Female; Humans; Leukemia; Liposomes; Lung Neoplasms; Male; Neoplasms; Orphan Drug Production; Phytoestrogens; Prostatic Neoplasms; Signal Transduction; Sitosterols

Topics: Glucose; Glucose Transporter Type 4; HEK293 Cells; Humans; Magnetic Resonance Spectroscopy; Mass Spectrometry; MCF-7 Cells; Molecular Mimicry; Muscle, Skeletal; Phosphatidylinositol 3-Kinases; Phytoestrogens; Proto-Oncogene Proteins c-akt; Signal Transduction; Sitosterols

Saraca asoca (Roxb.) de Wilde, Ashok, is a popular traditional plant used for gynecological disorders. In India, the juice of Ashok flowers is traditionally consumed as a tonic by women in case of uterine disorders. But despite the use, its estrogenic potency is not yet evaluated and thus lacks the scientific recognition and acclaim.. This study is designed to investigate the estrogenic potential of standardized ethanolic extract of Saraca asoca flowers (SAF) using ovariectomized (OVX) female albino Wistar rat model.. Saraca asoca flowers were extracted in ethanol using hot maceration technique and the extract was standardized in terms of content of four phytoestrogens like quercetin, kaempferol, β-sitosterol and luteolin using HPTLC technique. Safety of the extract was evaluated at a dose of 2000mg/kg body weight in female albino Wistar rats as per the OECD guidelines. Bilateral ovariectomy surgery was performed for the excision of both the ovaries. The OVX animals were treated with the ethanolic extract of SAF at three dose levels- 100mg/kg, 200mg/kg and 400mg/kg body weight in distilled water as a vehicle, orally once a day for two weeks. Estradiol valerate was employed as a modern drug for comparative evaluation of the results. Estrogenic potency was studied by assaying the activities of serum and plasma marker enzymes and hormones viz. G6PDH, LDH, 17β-estradiol, progesterone along with cholesterol, triglycerides and HDL, and vaginal cornification. The uterotrophic effect was evaluated by studying the histoarchitecture of the uterus, effect on uterine weight and changes in the levels of uterine glycogen content.. HPTLC revealed the presence of markers like quercetin, kaempferol, β-sitosterol and luteolin from the ethanolic extract of SAF. The content of the four markers was found to be 1.543mg/g, 0.924mg/g, 4.481mg/g and 2.349mg/g, respectively. SAF extract was found to be safe at an oral dose of 2000mg/kg body weight in rats. Among the three doses administered to ovariectomized rats, treatment with high dose was found to be more efficacious when compared with ovariectomized rats.. The findings of this study firmly support the estrogenic potency of ethanolic extract of SAF which may be by the reason of phytoestrogens.

Topics: Administration, Oral; Animals; Biomarkers; Chromatography, Thin Layer; Estradiol; Estrogen Replacement Therapy; Ethanol; Fabaceae; Female; Flowers; Glucosephosphate Dehydrogenase; Glycogen; Kaempferols; L-Lactate Dehydrogenase; Lipids; Luteolin; Medicine, Ayurvedic; Organ Size; Ovariectomy; Phytoestrogens; Phytotherapy; Plant Extracts; Plants, Medicinal; Progesterone; Quercetin; Rats, Wistar; Sitosterols; Solvents; Uterus; Vagina

Compounds with estrogenic potencies and their adverse effects in surface waters have received much attention. Both anthropogenic and natural compounds contribute to overall estrogenic activity in freshwaters. Recently, estrogenic potencies were also found to be associated with cyanobacteria and their blooms in surface waters. The present study developed and compared the solid phase extraction and LC-MS/MS analytical approaches for determination of phytoestrogens (8 flavonoids - biochanin A, coumestrol, daidzein, equol, formononetin, genistein, naringenin, apigenin - and 5 sterols - ergosterol, β-sitosterol, stigmasterol, campesterol, brassicasterol) and cholesterol in water. The method was used for analyses of samples collected in stagnant water bodies dominated by different cyanobacterial species. Concentrations of individual flavonoids ranged from below the limit of detection to 3.58 ng/L. Sterols were present in higher amounts up to 2.25 μg/L. Biological potencies of these phytoestrogens in vitro were characterized using the hERα-HeLa-9903 cell line. The relative estrogenic potencies (compared to model estrogen - 17β-estradiol) of flavonoids ranged from 2.25E-05 to 1.26E-03 with coumestrol being the most potent. None of the sterols elicited estrogenic response in the used bioassay. Estrogenic activity was detected in collected field water samples (maximum effect corresponding to 2.07 ng/L of 17β-estradiol equivalents, transcriptional assay). At maximum phytoestrogens accounted for only 1.56 pg/L of 17β-estradiol equivalents, contributing maximally 8.5% of the total estrogenicity of the water samples. Other compounds therefore, most likely of anthropogenic origin such as steroid estrogens, are probably the major drivers of total estrogenic effects in these surface waters.

Topics: Cholestadienols; Cholesterol; Cyanobacteria; Estradiol; Estrogens; Estrone; Fresh Water; Genistein; HeLa Cells; Humans; Isoflavones; Phytoestrogens; Phytosterols; Receptors, Estrogen; Sitosterols; Sterols; Tandem Mass Spectrometry; Water; Water Pollutants, Chemical

Focus of the study is to identify a safe alternate to Hormone Replacement Therapy by identifying the presence of β-sitosterol and stigmasterol in the hydroalcoholic extract of Bambusa bambos using HPTLC and RP-HPLC-PDA; by evaluating the estrogenic effects of extract containing β-sitosterol and stigmasterol on the growth of MCF-7 cells in vitro. Plant material was identified by DNA sequencing analysis. Presence of β-sitosterol and stigmasterol was confirmed by HPTLC and direct RP-HPLC-PDA. Peaks with retention time about 19.13 and 21.16min were found to be stigmasterol and β-sitosterol in extract. Extract was not cytotoxic to MCF-7 cells in any of the dilutions. It induced cell proliferation and all the dilutions except <500μg/ml have significantly increased cell multiplication. 15.6, 31.2, 62.5 and 125μg/ml of HEBB have shown influence on the proliferation rates similar to the standard 17β-estradiol. The results suggest that HEBB might be used as a safe alternative to estrogen replacement therapies.

Topics: Bambusa; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Ethnopharmacology; Humans; MCF-7 Cells; Molecular Structure; Phytoestrogens; Plant Extracts; Plant Leaves; Sitosterols; Stigmasterol

Phytoestrogens are produced by plants and may cause endocrine disruption in vertebrates. The present study hypothesizes that phytoestrogen exposure of female Siamese fighting fish (Betta splendens) may disrupt endogenous steroid levels, change agonistic behavior expression, and potentially also disrupt oocyte development. However, only the pharmacologic dose of β-sitosterol had a significant effect on opercular flaring behavior, while we did not find significant effects of β-sitosterol or genistein on steroids or gonads. These findings are in direct contrast with previous studies on the effects of phytoestrogens in female fish. Results of the current study support previous work showing that the effects of phytoestrogen exposure may be less acute in mature female B. splendens than in other fish.

Topics: Animals; Female; Fishes; Genistein; Oocytes; Phytoestrogens; Reproduction; Sitosterols

A gas chromatography with mass spectrometric detection (GC-MS) method was developed and optimized for the determination of 17 endocrine disrupting compounds (EDCs) in coastal water samples. The evaluated EDCs were from different origins and included estrogens, bisphenol A, alkylphenolethoxylates, alkylphenols, phytoestrogens and sitosterol (SITO). The EDCs were extracted from samples using Oasis HLB (Hydrophilic-Lipophilic Balance) cartridges and derivatized with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) added with 1% trimethylchlorosilane (TMCS). The validation parameters revealed that this method was highly specific for all assayed compounds (>99%) and the linearity of the calibration curves showed a correlation higher than 0.99. The detection limits were at low ng/L level and the recovery rates were higher than 70%. The performance of the method was checked using coastal water samples taken every 2 months during 2009-2010 from the Douro River estuary and the Porto coastline (Portugal). These data revealed that approximately 98.0% of the analyzed compounds showed levels above their limits of detection (LODs). The measured estrogens (2-20 ng/L) and industrial pollutants (up to 1.1 μg/L) were in biologic hazardous concentrations. Besides, a clear seasonal pattern of fluctuation was established for phytoestrogens and SITO. The physicochemical data, namely the amounts of nitrates, nitrites and phosphorous, confirmed the low water quality of this area.

Topics: Atlantic Ocean; Endocrine Disruptors; Estuaries; Gas Chromatography-Mass Spectrometry; Phytoestrogens; Portugal; Reproducibility of Results; Rivers; Seawater; Sitosterols; Water Pollutants, Chemical

Aloes are now considered a very interesting source of bioactive compounds among which phytosterols should play a major role. The present study is an attempt to investigate the hypocholesterolemic activity of Aloe vera associated with its impact on the reproductive status of juvenile goldfish. Therefore, the short- and long-term effects of feeding supplementary diet containing aloe components (20 mg aloe/g diet; 2%) on plasma lipids, plasma vitellogenin, and hepatic estrogen receptor α/β1 mRNA levels in goldfish were examined. Results of GC-MS for phytosterols show high abundance of β-sitosterol in freeze-dried powder of Aloe vera whole leaves. Moreover, a 2% aloe powder dietary supplement was not found estrogenic in juvenile goldfish after either 7- or 30-day treatment, but was consistent in plasma hypocholesterolemic effects following long-term exposure. The present data further support that plasma cholesterol modulation induced by phytosterols may not be related to estrogen-like activity.

Topics: Aloe; Animals; Biomarkers; Goldfish; Gonads; Hypothalamo-Hypophyseal System; Lipids; Liver; Phytoestrogens; Plant Preparations; Receptors, Estrogen; RNA, Messenger; Sitosterols; Vitellogenins

Phytoestrogens are plant compounds that can act as endocrine disruptors in vertebrates. Biologically active levels of phytoestrogens have been found in aquatic habitats near wood pulp and paper mills, biofuel manufacturing plants, sewage-treatment plants, and agricultural fields. Phytoestrogens are known to cause hormonal and gonadal changes in male fish, but few studies have connected these effects to outcomes relevant to reproductive success. In one experiment, we exposed sexually mature male fighting fish Betta splendens to environmentally relevant (1 μg L(-1)) and pharmacological concentrations (1000 μg L(-1)) of the phytoestrogen genistein as well as to a positive control of waterborne 17β-estradiol (E2; 1 μg L(-1)), and a negative control of untreated water. In a second experiment, we exposed male B. splendens to environmentally relevant concentrations (1 μg L(-1)) of genistein and β-sitosterol singly and in combination as well as to the positive and negative controls. All exposures were 21 days in duration. We measured sex-steroid hormone levels, gonadosomatic index (GSI), sperm concentration and motility, and fertilization success in these fish. We found that exposure to genistein did not affect circulating levels of the androgen 11-ketotestosterone or the estrogen E2 relative to negative-control fish. We also found that neither of the compounds nor their mixture affected GSI, sperm concentration or motility, or fertilization success in exposed fish relative to negative-control fish. However, fish exposed to phytoestrogens showed some evidence of fewer but more motile sperm than fish exposed to the positive control E2. We conclude that sexually mature male B. splendens are relatively immune to reproductive impairments from short-term exposure to waterborne phytoestrogens.

Topics: Animals; Endocrine Disruptors; Estradiol; Fertilization; Genistein; Male; Perciformes; Phytoestrogens; Sitosterols; Sperm Motility; Testis; Testosterone; Water Pollutants, Chemical

Endogenous estrogens are known to affect the activity of monoamine neurotransmitters in vertebrate animals, but the effects of exogenous estrogens on neurotransmitters are relatively poorly understood. We exposed sexually mature male fighting fish Betta splendens to environmentally relevant and pharmacological doses of three phytoestrogens that are potential endocrine disruptors in wild fish populations: genistein, equol, and β-sitosterol. We also exposed fish to two doses of the endogenous estrogen 17β-estradiol, which we selected as a positive control because phytoestrogens are putative estrogen mimics. Our results were variable, but the effects were generally modest. Genistein increased dopamine levels in the forebrains of B. splendens at both environmentally relevant and pharmacological doses. The environmentally relevant dose of equol increased dopamine levels in B. splendens forebrains, and the pharmacological dose decreased norepinephrine (forebrain), dopamine (hindbrain), and serotonin (forebrain) levels. The environmentally relevant dose of β-sitosterol decreased norepinephrine and dopamine in the forebrain and hindbrain, respectively. Our results suggest that sources of environmental phytoestrogens, such as runoff or effluent from agricultural fields, wood pulp mills, and sewage treatment plants, have the potential to modulate neurotransmitter activity in free-living fishes in a way that could interfere with normal behavioral processes.

Topics: Analysis of Variance; Animals; Brain; Chromatography, High Pressure Liquid; Dopamine; Equol; Genistein; Isoflavones; Male; Norepinephrine; Perciformes; Phytoestrogens; Serotonin; Sitosterols; Vesicular Monoamine Transport Proteins; Water Pollutants, Chemical

Phytoestrogens are natural components of plant-based food items with beneficial health effects. The aim of the present study was to investigate the chronic effects of dietary phytoestrogens, genistein (8 mg kg(-1) day(-1)) and beta-sitosterol (50 mg kg(-1) day(-1)), on the weight regulation of the mink (Mustela vison). The parental generation was exposed from August 2002 to May-June 2003 to either beta-sitosterol or genistein, while the kits were exposed through gestation and lactation. Food consumption and body masses were monitored monthly. Plasma lipid, glucose, total protein and hormone (ghrelin, leptin, triiodothyronine and thyroxine) concentrations were measured from the parents in August 2002, January 2003 and at the end of the experiment in May-June 2003 when the kits were 21 days of age. Relative food intake was higher in the beta-sitosterol-exposed minks than in the control or genistein minks in September 2002. Plasma leptin and total protein concentrations were lower in the beta-sitosterol kits compared to the control kits. Furthermore, plasma ghrelin levels and liver phosphorylase activities of the mink kits were higher due to genistein exposure. In mink kits, exposure to both phytoestrogens reduced the plasma thyroxine concentrations. The kidney glycogen concentrations and the muscle phosphorylase activities of phytoestrogen-treated adult minks were elevated. The results of this study suggest that minks are sensitive to perinatal phytoestrogen exposure.

Topics: Animals; Female; Genistein; Ghrelin; Leptin; Male; Mink; Peptide Hormones; Phytoestrogens; Sitosterols

We investigated the behavioral effects of exposure to waterborne phytoestrogens in male fighting fish, Betta splendens. Adult fish were exposed to a range of concentrations of genistein, equol, beta-sitosterol, and the positive control 17beta-estradiol. The following behaviors were measured: spontaneous swimming activity, latency to respond to a perceived intruder (mirror reflection), intensity of aggressive response toward a perceived intruder, probability of constructing a nest in the presence of a female, and the size of the nest constructed. We found few changes in spontaneous swimming activity, the latency to respond to the mirror, and nest size, and modest changes in the probability of constructing a nest. There were significant decreases, however, in the intensity of aggressive behavior toward the mirror following exposure to several concentrations, including environmentally relevant ones, of 17beta-estradiol, genistein, and equol. This suggests that phytoestrogen contamination has the potential to significantly affect the behavior of free-living fishes.

Topics: Aggression; Animals; Behavior, Animal; Equol; Estradiol; Female; Fishes; Genistein; Isoflavones; Male; Nesting Behavior; Phytoestrogens; Sexual Behavior, Animal; Sitosterols; Swimming; Water Pollutants, Chemical

The aim of the present study was to examine the reproductive effects of two perorally applied phytoestrogens, genistein (8 mg/kg/day) and beta-sitosterol (50 mg/kg/day), on the mink (Mustela vison) at human dietary exposure levels. Parental generations were exposed over 9 months to these phytoestrogens and their offspring were exposed via gestation and lactation. Parents and their offspring were sampled 21 days after the birth of the kits. Sex hormone levels, sperm quality, organ weights, and development of the kits were examined. The exposed females were heavier than the control females at the 1st postnatal day (PND). The control kits were heavier than the exposed kits from the 1st to the 21st PND. Phytoestrogens did not affect the organ weights of the adult minks, but the relative testicular weight of the exposed kits was higher than in the control kits. The relative prostate weight was higher and the relative uterine weight lower in the beta-sitosterol-exposed kits than in the control kits. Moreover, the plasma dihydrotestosterone levels were lower in the genistein-exposed male kits compared to the control male kits. This study could not explain the mechanisms behind these alterations. The results indicate that perinatal phytoestrogen exposures cause alterations in the weight of the reproductive organs of the mink kits.

Topics: Administration, Oral; Aging; Animals; Animals, Newborn; Body Mass Index; Dihydrotestosterone; Drug Administration Schedule; Estradiol; Female; Finland; Genitalia, Female; Genitalia, Male; Gonadal Steroid Hormones; Male; Mink; Organ Size; Phytoestrogens; Pregnancy; Prenatal Exposure Delayed Effects; Reproduction; Semen; Sex Characteristics; Sitosterols; Species Specificity; Sperm Count; Testis; Testosterone

Although many dietary studies have focused on breast cancer risk, few have examined dietary influence on tumor characteristics such as estrogen receptor (ER) status. Because phytoestrogens may modulate hormone levels and ER expression, we analyzed ER status and phytoestrogen intake in a case-case study of 124 premenopausal breast cancer patients. We assessed intake with a food-frequency questionnaire and obtained ER status from medical records. Rather than focusing on risk, we evaluated whether low intakes were more strongly associated with ER-negative tumors than with ER-positive disease. In logistic regression adjusting for potential confounders, threefold greater risks of ER-negative tumors relative to ER-positive tumors were associated with low intake of the isoflavones genistein (odds ratio, OR=3.50; 95% confidence interval, CI=1.43-8.58) and daidzein (OR=3.10; 95% CI=1.31-7.30). Low intake of the flavonoid kaempferol (OR=0.36; 95% CI=0.16-0.83), the trace element boron (OR=0.33; 95% CI=0.13-0.83), and the phytosterol beta-sitosterol (OR=0.42; 95% CI=0.18-0.98) were associated with decreased risk of ER-negative tumors relative to ER-positive disease. Other phytoestrogens were not significantly associated with ER status. Thus, in premenopausal patients, some phytoestrogens may affect breast carcinogenesis by influencing ER status. Such findings suggest new directions for mechanistic research on dietary factors in breast carcinogenesis that may have relevance for prevention and clinical treatment.

Topics: Adult; Anticarcinogenic Agents; Boron; Breast Neoplasms; Diet; Female; Genistein; Humans; Hypolipidemic Agents; Isoflavones; Kaempferols; Middle Aged; Nutritional Status; Odds Ratio; Phytoestrogens; Premenopause; Receptors, Estrogen; Risk Factors; Sitosterols; Surveys and Questionnaires

Phytosterols or plant sterols (PS) are consumed as natural remedies and margarines by the general population in developed countries to lower elevated serum cholesterol levels. They are also present in high concentrations in pulp mill effluents. The aim of the study was to screen the endocrine and metabolic parameters of the European polecat (Mustela putorius) for the effects of PS. The results showed an increase in the plasma estradiol and TH levels with no effects on the hypophyseal regulatory hormones. The plasma ghrelin levels decreased. PS also affected intermediary metabolism. The liver glycogen content increased as did the kidney glucose-6-phosphatase activity. The liver lipase esterase activity, on the other hand, decreased due to PS. In serum lipids the total cholesterol did not change, but the low-density lipoprotein levels increased and the high-density lipoprotein-cholesterol ratio decreased. PS had widespread previously unreported effects on the physiology of the polecat. The multiple effects indicate the need of a thorough risk assessment of the effects and interactions of PS.

Topics: Animals; Body Weight; Carnivora; Dose-Response Relationship, Drug; Endocrine Glands; Estradiol Congeners; Estrogens, Non-Steroidal; Female; Glycogen; Hormones; Hypolipidemic Agents; Inactivation, Metabolic; Isoflavones; Kidney; Lipids; Liver; Male; Metabolism; Organ Size; Phytoestrogens; Phytosterols; Plant Preparations; Sitosterols

Administration of estradiol/progesterone to ovariectomized animals significantly increased the uterine weight, RNA, DNA and protein concentrations. Similarly, administration of beta-sitosterol alone or in combination with estradiol caused a marked increase in the above parameters and the maximum influence was evident only after median and high dose treatments. However, administration of median/high dose of beta-sitosterol along with progesterone accentuated only the RNA and protein concentrations but exerted an inhibitory effect on sitosterol-induced increment in uterine weight and DNA concentrations.

Topics: Animals; DNA; Estradiol; Estrogens; Estrogens, Non-Steroidal; Female; Isoflavones; Organ Size; Ovariectomy; Phytoestrogens; Plant Preparations; Progesterone; Proteins; Rats; Rats, Wistar; RNA; Sitosterols; Uterus

Phytoestrogenic substances have previously been isolated and identified in two alcoholic beverages: bourbon and beer. To delineate the relative potencies of the estrogenic substances of plant origin thus far identified in these commonly consumed alcoholic beverages, we evaluated the ability of biochanin A, beta-sitosterol, genistein, and daidzein to bind to cytosolic estrogen receptor binding sites. The in vitro studies demonstrated that each of the contained substances was capable of effectively competing for cytosolic estrogen receptor binding sites of rat liver and uterus. Further, the two phytoestrogenic constituents of bourbon, beta-sitosterol and biochanin A, were less potent than those present in beer. Given the high concentration of beta-sitosterol in bourbon, we chose to evaluate the estrogenicity of beta-sitosterol in vivo using ovariectomized rats. beta-sitosterol was administered either daily or intermittently at 3 doses, based on amounts previously determined to be present in bourbon. The in vivo studies demonstrated that beta-sitosterol is capable of producing a weak estrogenic effect only at the lowest dose (6.2 micrograms/dl) administered intermittently. These responses suggest that beta-sitosterol may be weakly estrogenic at low doses, but is unable to maintain such an effect at higher doses.

Topics: Alcoholic Beverages; Animals; Beer; Cytosol; Dose-Response Relationship, Drug; Estrogens; Estrogens, Non-Steroidal; Female; Genistein; Isoflavones; Liver; Male; Phytoestrogens; Plant Preparations; Rats; Rats, Wistar; Receptors, Estrogen; Sitosterols; Uterus

There is considerable evidence that several plant metabolites have estrogenic properties. Given that many alcoholic beverages are made from plants which have been shown to possess estrogenic activity, we considered the possibility that alcoholic beverages may contain estrogenically active substances. To evaluate this hypothesis we first extracted and then used gas chromatography/mass spectrometry to identify two phytoestrogens, biochanin A and beta-sitosterol in the bourbon extracts. Based on these findings we suggest that the feminization observed in chronic male alcoholics with liver disease may reflect, at least in part, the presence of biologically active phytoestrogens in the alcoholic beverages they consume.

Topics: Alcoholic Beverages; Chemical Phenomena; Chemistry; Estrogens; Estrogens, Non-Steroidal; Gas Chromatography-Mass Spectrometry; Genistein; Isoflavones; Phytoestrogens; Plant Preparations; Sitosterols