Effects Of Phytoestrogens Research Articles

PERSPECTIVES FOR THE USE OF PLANT RAW MATERIALS OF THE CLOVER MEADOW (TRIFOLIUM PRATENSE L.) IN PHARMACY

Background. The creation and registration of original medicines based on plant raw materials are becoming promising areas in pharmaceutical practice. Clover meadow (Trifolium pratense L.) has been used in folk medicine for a long time, due to the content of many biologically active substances with Therapeutic properties. It grows over large areas; extracts are easy to obtain from plant raw materials and have a certain economic attractiveness. In this regard, compounds extracted from meadow clover can be considered as potential precursors for the development of new promising pharmaceuticals. Aim. Carrying out a narrative review on the Perspectives of the use of biologically active substances extracted from the plant raw materials of meadow clover in pharmaceutical practice. Material and methods. The scientific publications of the PubMed biomedical research database are analyzed. Results. Meadow clover (Trifolium pratense L.) is a widespread perennial herbaceous plant belonging to the pharmacopoeia group. Extracts obtained from plant raw materials have a wide range of biological activity. The largest proportion of them are isoflavones, flavonoids, saponins, clovamides and phenolic acids. Isoflavones have a phytoestrogenic effect, and in this regard, they are successfully used in the treatment of diseases of the reproductive system. In addition, their anti-inflammatory, reparative properties have been proven; they can be used for the prevention and recovery of metabolic disorders. Flavonoids, saponins, clovamides and phenolic acids have antioxidant and antiplatelet effects. Conclusion. Among biologically active substances extracted from meadow clover, the greatest use in pharmacological practice was noted for isoflavones. At the same time, there are a few other potentially effective compounds with known medicinal properties. Their further study is required in order to create new original medicines

Ameliorative Effects of Phyto-estrogen ‘Genistein’, Homeopathic Combination ‘R-85’and Captopril on Body Weight, Organ Weight, Feed and Water Intake in L-NAME Induced Hypertensive Wistar Rats

Hypertension is associated with the development and progression of severe damage to organs. Meager studied has been found on the effect of Phyto-estrogen ‘genistein’ and homeopathic combination ‘R-85’ as antihypertensive action which may aid in main therapy of hypertension. Thus, present study aims to evaluate the effect of ‘genistein’, ‘R-85’ and ‘captopril’ on body weight, organ weight feed and water intake in Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) induced hypertensive male wistar rats. After acclimatization, the male wistar rats were divided into 5 groups of 5 rats in each group. The rats except control group (group-I) were treated with L-NAME (@50mg/kg, in drinking water, group-II), L-NAME + Genistein (@50mg/kg, per os, group-III), L-NAME + R-85 (@ 5 drops, twice daily, group-IV) and L-NAME + Captopril (@50 mg/kg, per os, group-V) daily for 42 days. The study was conducted for a period of 42 days. During the experimental period, weight of rats, feed intake and water intake was measured weekly. At the end of the experimental period, rats were sacrificed andheart, kidneys and liver were weighed. After treatment with genistein, R-85 and captopril an increase in body weight was found as compared to L-NAME group. On similar treatment there was an increase in feed intake per 100 g of rat was found compared to L-NAME hypertensive group per week. Unlike feed intake, treatments decrease the water intake per 100 g of rat compared to L-NAME group per week. A significant increase in the relative weights of the liver and kidney was found in L-NAME group compared to control. Whereas, treatment with R-85 and captopril significantly decreased the relative weight of liver and kidney as compared to L-NAME group. Thus finding of the present study discloses ameliorative effect of genistein, R-85 and captopril on hypertensive rats.

Phytoestrogens in Menopausal Hot Flashes: A Review Article

Background: Menopause is a biopsychosocial phenomenon in a woman’s life, and it occurs at about the age of 48-55 years. Factors such as smoking, the number of children, early puberty, and social class can cause early natural menopause. Symptoms that occur during menopause include headache, mood disorders, insomnia, distraction, hot flashes, vaginal dryness, and sweating. The most common symptom is hot flashes, which affect 85% of women with menopause. Recently, people are showing more tendencies toward alternative therapies and herbs phytoestrogens. Objective: This review aims to introduce the mechanism of herbal phytoestrogens controlling hot flashes during menopause. Methods: Our searches were performed in the databases of PubMed, Scopus, and Cochrane. English clinical trials, that investigated the effects of phytoestrogen plants individually or in combination on the treatment of hot flashes in menopause were analyzed. After reviewing articles and meeting the inclusion and exclusion criteria, 18 articles were selected. Results: In this study, 18 clinical trials of 2351 female patients were analyzed. The phytoestrogen plants studied include soy, red clover, cohosh, hops, flax, pomegranate, anise, and Vitex Agnus. Conclusion: Studies have shown the beneficial effects of phytoestrogens in controlling hot flashes, but in some cases, including soybeans, there are contradictory effects. Therefore, more clinical trials are needed to achieve reliable results to confirm the phytoestrogen effects of herbal medicines.

The Pros and Cons of Estrogens in Prostate Cancer: An Update with a Focus on Phytoestrogens.

The role of estrogens in prostate cancer (PCa) is shrouded in mystery, with its actions going from angelic to devilish. The findings by Huggins and Hodges establishing PCa as a hormone-sensitive cancer have provided the basis for using estrogens in therapy. However, despite the clinical efficacy in suppressing tumor growth and the panoply of experimental evidence describing its anticarcinogenic effects, estrogens were abolished from PCa treatment because of the adverse secondary effects. Notwithstanding, research work over the years has continued investigating the effects of estrogens, reporting their pros and cons in prostate carcinogenesis. In contrast with the beneficial therapeutic effects, many reports have implicated estrogens in the disruption of prostate cell fate and tissue homeostasis. On the other hand, epidemiological data demonstrating the lower incidence of PCa in Eastern countries associated with a higher consumption of phytoestrogens support the beneficial role of estrogens in counteracting cancer development. Many studies have investigated the effects of phytoestrogens and the underlying mechanisms of action, which may contribute to developing safe estrogen-based anti-PCa therapies. This review compiles the existing data on the anti- and protumorigenic actions of estrogens and summarizes the anticancer effects of several phytoestrogens, highlighting their promising features in PCa treatment.

The Potentials of Phytoestrogen Compounds in Aquaculture – A Review

Abstract All organisms require the ability to engage in either sexual or asexual reproduction in order to ensure their own survival. In aquaculture, when one sex outgrows the other faster, farmers use hormones to stimulate growth. Furthermore, the production of fish based on sexual dimorphism is predominantly executed through the utilization of estrogens and androgens. Environmentally, these compounds may pollute the ecosystem and cause endocrine system alterations that cause harmful effects; thus, they must be handled carefully to assure environmental, biological, and food safety. Phytoestrogens as natural non-steroidal phenolic plant chemicals that resemble 17-β-estradiol, could be employed as a safe alternative source of natural estrogens. The phytoestrogens have many biological effects due to their ability to compete with estrogen receptors, but they may negatively affect fish production, reproduction, and behaviors under controlled conditions. Thus, the current literature emphasizes on the beneficial effects of phytoestrogens on aquatic animal performance, behaviors, and some reproductive features.

The Impact of Phaleria macrocarpa Fruit Flavonoid Extract on Endometrial Thickness in Mice Menopausal Model

This study aims to determine how the effect of flavonoid phaleria macrocarpa fruit extract on the endometrial thickness of Mus musculus which is used as an experimental animal with a menopause model. This study employed a randomized post-test-only control group design on 32 female mice. Ovariectomy simulated menopause, followed by treatment with flavonoid from Phaleria macrocarpa fruit extract. Post-observariectomized, follicle-stimulating hormone levels indicated menopausal status. Hematoxylin-Eosin methods assessed endometrial thickness. The result indicated reduced endometrial thinning in the positive control group (K+). Conversely, the treatment group (P1-P4) exhibited increased endometrial thickness post-flavonoid extract administration. Ovariectomized-induced estrogen decline resulted in reduced endometrial thinning, mimicking menopausal conditions. Statistically, flavonoid extract administration increased endometrial thickness in ovariectomized-induced menopausal mice, with optimal effect observed at 7.5 mg/mice/day for 14 days. The preferred intervention dose for altering endometrial thickness in menopausal conditions was identified as P1 (3.75 mg/mice/day). In conclusion, a flavonoid from Phaleria macrocarpa fruit extract mitigates endometrial thinning in the menopausal mice model. For implication in menopausal women, clinical trials need to be conducted to evaluate the dosage of these flavonoids for their potential as a natural SERM (Selective Estrogen Receptor Modulator) before clinical application in managing endometrial health. Additionally, research on molecular effects particularly regarding ER (Estrogen Receptors) in the endometrial organ, is needed to confirm their phytoestrogenic effect.

Dietary anthocyanin is associated with a lower prevalence of hyperuricemia independently of metabolic syndrome among females: Results from NHANES 2007-2010 and 2017-2018.

Known for anti-inflammatory and antioxidant properties, flavonoid has phytoestrogenic effects, but it is unclear whether its role in hyperuricemia and metabolic syndrome (MetS) differs by gender. Moreover, given the strong association between hyperuricemia and MetS, we aimed to explore whether flavonoid is a protective factor for hyperuricemia, independently of MetS, in different genders. Data for 2007-2010 and 2017-2018 were obtained from the National Health and Nutrition Examination Survey (NHANES) and the Food and Nutrient Database for Dietary Studies (FNDDS). To assess the association among flavonoid, hyperuricemia, and MetS, multivariate logistic regression and subgroup analyses were conducted. Besides, to investigate whether the association between flavonoid and hyperuricemia was independent of MetS, multivariate logistic regression models were further conducted to explore the association between flavonoid and MetS among females with hyperuricemia and to investigate the association between flavonoid and hyperuricemia among females after excluding MetS. Among 5356 females, anthocyanin intake was inversely associated with the prevalence of hyperuricemia (Q4 vs. Q1: OR 0.49, 95% CI 0.31 to 0.76), and MetS (Q4 vs. Q1: OR 0.68, 95% CI 0.50 to 0.93). Furthermore, subgroup analyses showed the beneficial association between anthocyanin and hyperuricemia among females aged 40 to 59 years and menopausal. However, among 5104 males, no significant association was observed after adjustment for covariates (Q4 vs. Q1: OR 0.81, 95% CI 0.56 to 1.18). While in 372 females with hyperuricemia, no significant association was found between MetS and anthocyanin (Q4 vs. Q1: OR 0.88, 95% CI 0.31 to 2.49). Meanwhile, among 3335 females after excluding MetS, there was still a significant association between anthocyanin and a lower prevalence of hyperuricemia (Q4 vs. Q1: OR 0.38, 95% CI 0.17 to 0.85). Dietary anthocyanin is associated with a lower prevalence of hyperuricemia independently of MetS among females. Foods rich in anthocyanin should be emphasized for females, especially those aged 40 to 59 years and menopausal, which may be of potential significance in the prevention of hyperuricemia.

Phytoestrogens: Chemistry, potential health benefits, and their medicinal importance.

Phytoestrogens, also known as xenoestrogens, are secondary metabolites derived from plants that have similar structures and biological effects as human estrogens. These compounds do not directly affect biological functions but can act as agonists or antagonists depending on the level of endogenous estrogen in the body. Phytoestrogens may have an epigenetic mechanism of action independent of estrogen receptors. These compounds are found in more than 300 plant species and are synthesized through the phenylpropanoid pathway, with specific enzymes leading to various chemical structures. Phytoestrogens, primarily phenolic compounds, include isoflavonoids, flavonoids, stilbenes, and lignans. Extensive research in animals and humans has demonstrated the protective effects of phytoestrogens on estrogen-dependent diseases. Clinical trials have also shown their potential benefits in conditions such as osteoporosis, Parkinson's disease, and certain types of cancer. This review provides a concise overview of phytoestrogen classification, chemical diversity, and biosynthesis and discusses the potential therapeutic effects of phytoestrogens, as well as their preclinical and clinical development.

Effects of Mixed Pasture Legume Phytoestrogens on Superovulatory Response and Embryo Quality in Angus Cows.

Ovulation and artificial insemination rates have been observed to decrease in sheep and cows when exposed to dietary phytoestrogens at concentrations greater than 25 mg/kg DM. A grazing trial was undertaken to investigate the effects of coumestrol and other key phytoestrogens on the superovulatory response, embryo numbers and quality in beef cows grazing legume pastures. A 7-week controlled grazing trial was conducted with legume and ryegrass pasture treatments, with cows exposed to legumes at two timed treatments, 4 and 7 weeks. Twenty Angus cows were subjected to a conventional estrus synchronization and superovulation protocol. Embryos were recovered via conventional uterine body flushing 7 days post artificial insemination (AI). Numerous phytoestrogens were identified in both pasture and plasma samples, including coumestrol and formononetin. Concentrations of phytoestrogens in the pasture ranged from 0.001 to 47.5 mg/kg DM and 0 to 2.6 ng/mL in plasma. Approximately 50% of cows produced viable embryos 7 days post AI. A significant interaction between the effect of treatment groups on the embryo stage was observed (p < 0.05). The results suggest that concentrations of >25 mg/kg DM of phytoestrogens less than 20 days preceding AI may negatively affect oocyte developmental competence, reduce progesterone production and thus contribute to early embryonic loss.

"Effect of Phytoestrogens on Some Reproductive Physiology and Performance"

"Effect of Phytoestrogens on Some Reproductive Physiology and Performance"

Abstract 3171: The effect of estrogen and phytoestrogens in Inflammatory breast cancer

Abstract Inflammatory breast cancer is an aggressive and lethal type of breast cancer. Frequently, this cancer is diagnosed in an advanced stage with metastasis. IBC diagnosis is associated with a worse survival rate than other types of breast cancer. The presence of dermal and stromal tumor emboli blocking the lymphatic vessels under the skin is considered a hallmark of IBC and assumed to be responsible for the high metastatic behavior and aggressiveness of IBC disease. To this date, there are no effective targeted therapeutics, especially for those patients that account for approximately 20-40% of IBC cases with triple-negative breast cancer (TNBC) classification. Several studies have shown that estrogen can exert non-genomic effects in IBC and non-IBC TNBC, mediated by the expression of alternate estrogen receptors including estrogen receptor alpha-36, and GPR30. In this context, estrogen can activate non-genomic signaling pathways involved in the acquisition of oncogenic phenotypes such as increased motility and invasion in IBC cells. Phytoestrogens, naturally derived structural analogs to 17β-estradiol (E2), were evaluated as an alternative treatment option using in vitro IBC cell models (SUM149 and SUM190). Given the estrogenic properties of phytoestrogens, the drugs were hypothesized to interact with targets in pathways similar to E2 in non-genomic signaling. Several phytoestrogens including coumestrol (Cou) can induce a cytotoxic effect in TNBC. We hypothesize (1) that estrogen non-genomic signaling has an active role in the aggressive metastatic phenotype of IBC, and (2) that Cou has anticancer activity by inhibiting estrogen non-genomic signaling in IBC. To test these hypotheses, IBC cells were treated with E2 or Cou to determine their effects on the activation of downstream kinases by western blot and phospho-kinase array assays. In addition, transcriptional effects upon treatment with Cou were identified using RNA-seq. A dose-response curve in 2D and 3D models was generated to determine the half-maximal inhibitory concentration (IC50) of Cou. Finally, treatment using the IC50 of Cou caused a decrease in cell viability in the TNBC cell line. Also, in comparison to E2, Cou decreases migration, proliferation, and tumor emboli formation in IBC cell lines. In addition, IBC cells were treated using monotherapy and combination therapy with phytoestrogens including Cou, genistein (GN), and/or 8-prenylnaringenin (8-PN). Observed reductions of cell viability in IBC cell lines treated with the different phytoestrogens and combinations make them worthy of further characterization as anti-cancer therapies in in vitro and in vivo models. In summary, IBC cells are responsive to E2 making this signaling pathway attractive for the development of innovative therapeutic strategies with phytoestrogens as potential candidates for treatment. Citation Format: Esther A. Peterson-Peguero, Keishla Rodriguez-Martir, Madeline Ganshert, Dalissa Negron-Figueroa, Ayeisha N. Colon-Ortiz. The effect of estrogen and phytoestrogens in Inflammatory breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3171.

Botanicals in Alleviating Menopause

Background: Estrogens play a pivotal role in maintaining human health whose imbalance leads to several disorders in the human system and most of these effects are observed during menopause. A vast number of vasomotor symptoms have been observed among which hot flushes is the most common. Though numerous medical regimens are available, Hormone Replacement Therapy (HRT) is the most preferred one owing to its effectiveness in relieving menopausal symptoms. But it might pave way for various other illnesses such as cancers in the reproductive system and cardiac problems. Hence, a different strategy is required, which opened the vision towards Complementary and Alternative Medicine which is preferred throughout the world due to its efficacy and safety in varied medical issues. Methods: Data were collected from sources such as Scopus, PubMed, Science Direct, Web of Science, Scientific Electronic Library Online, Google Scholar, EMBASE, PubChem and Dr. Duke’s phytochemical and ethnobotanical databases. Results: An array of plants were listed encompassing the etymology, botany of the plants, chief phytochemicals present with estrogenic potential and medicinal benefits. Vital phytoestrogens reported were flavonoids, coumestans, stilbenes, chalcones and lignans. Phytoestrogenic compounds were reported to empower women’s health during and after menopause. Conclusion: These botanicals are considered safe due to their low or no side effects but intensive research is necessitated to validate the effectiveness and safety of phytoestrogens.

Is there a difference between the effects of phytoestrogens and non-phytoestrogens medicinal plants on sexual health? A systematic review and meta-analysis.

Background: The quality of life of a person and her sexual partner is impacted by sexual function. Sexual function disorders have a significant prevalence in society. There are different treatments for sexual disorders, including herbal therapies. Objective: This study aimed to do a comparison of phytoestrogens and non-phytoestrogens medicinal plant's effects on sexual health in pre- and postmenopausal women. Materials and Methods: This systematic review and meta-analysis was performed to identify relevant articles in electronic databases such as Web of Science, Scopus, PubMed, Cochrane Library, Google Scholar, and SID for English- and Persian-language articles published up to December 2021. The Cochrane collaboration tool was used to assess the risk of bias. Heterogeneity was assessed using I2 statistics. Results: Of 5428 records retrieved by searching the databases, after removing duplicate and irrelevant articles, 39 articles were included based on the inclusion criteria in the study. Finally, 18 articles with 1299 participants were included in the meta-analysis. 18 randomized clinical trial studies of phytoestrogens (n = 13) and non-phytoestrogens (n = 5) plants that used the female sexual function index questionnaire and reported the mean difference (MD) and standard deviation were included in the meta-analysis. The effects of phytoestrogens and non-phytoestrogens plants on the sexual health of postmenopausal women appear to differ significantly from one another, according to the meta-analysis (MD = 7.59; 95% CI = 4.56-10.60 and MD = 3.19; 95% CI = 1.25-5.13, respectively) but this difference was not observed in premenopausal women. Conclusion: The effect of phytoestrogens plants is more in menopausal women, and they can be advised to use these herbs.

Α novel method for the efficient simultaneous quantification of 67 phytoestrogens in plants and foodstuffs

The significant beneficial effects of phytoestrogens on human and animal health have emerged the necessity to develop a sensitive, accurate and rapid method for their efficient quantitation in human and animal foods. Study herein concerns the development of a novel analytical method using high-performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) that allows the simultaneous quantitation of 67 natural phytoestrogens. The novel method was fully validated through the determination of the following parameters: selectivity, sensibility, recovery, precision, accuracy of detection and quantification limits for each analyte. Specifically, the novel method proved accurate displaying linear response with R2 values ≥ 0.9991, quantitation limits from 5.5 to 331.8 ng/mL for 98.5% of analytes, recovery values ranging between 64.8% and 150.3%, while the precision and accuracy scores remained below 20% for most analytes. The method was successfully applied on the following plant samples used in human and/or animal diet belonging to Fabaceae plant family: Trifolium repens, Vicia sativa, Pisum sativum and Glycine max (soybean meal). Furthermore, the novel method was applied for the determination of the phytoestrogenic content of two animal feeds (for livestock and fishes) and two foodstuffs (chicken meat and fish fillet).

The effect of phytoestrogen (lignan) on the levels of some hormo-nal parameters in white female rats induced osteoporosis

The current study aimed to evaluate the effectiveness of the phytoestrogen (lignan) in some hormonal parameters of white female rats induced osteoporosis with Prednisolone. The present study included two main experiments, In the first experiment 50 adult white female rats were divided into two groups, The first group G1 was considered a control group and the second group, G2 was induced into osteoporosis by Prednisolone at a dose of 40 mg/kg of body weight For two months. The second main experiment divided the remaining animals (from the first group of the first experiment into three subgroups) and the remaining animals (from the second group of the first experiment into two subgroups): negative control group C was dosed with distilled water, group T1 was considered a positive control that was continued with Prednisolone at a dose of 40 mg/kg of body weight, group T2, was induced osteoporosis and administered the phytoestrogens(lignan) at a dose of 20 mg/kg, the healthy T3 group was administered the phytoestrogens(lignan) at a dose of 20 mg/kg, and the T4 group was administered the phytoestrogens(lignan) at a dose of 20 mg/kg. And Prednisolone at a dose of 40 mg/kg simultaneously for 30 days. After the end of the second experiment, the weights of the animals were recorded and then anesthetized with chloroform withdrawal blood samples from the heart directly for hormonal tests that represent estrogen, FSH, LH. The results showed a significant decrease (P&lt;0.05) in each of the average estrogen, FSH, LH level in the T1 group (positive control) when comparing to the negative group. while the cause of the phytoestrogen(lignan) improved The hormonal parameters and showed a significant increase (P&lt;0.05) in estrogen, FSH, LH level in T2,T3,T4groups when comparing to T1 (positive control). We conclude from the current study the effective and positive role shown by phytoestrogens(lignan) in improving and enhancing the hormonal parameters and reducing the negative effects of induced osteoporosis in white female rats.

Association between Phytoestrogen Consumption and Female Reproductive Health: A Systematic Review of Experimental Models

AbstractPhytoestrogens have been shown as promising therapeutic agents for the treatment of menopausal symptoms, osteoporosis, breast cancer, and cardiovascular diseases. However, due to its unique chemical structure, phytoestrogen may cause unintended estrogenic and/or antiestrogenic effects on the human body, especially with regard to female reproductive health and performance. Hence, this systematic review aims to provide a critical evaluation of in vitro and in vivo evidence from the literature regarding the adverse effects of phytoestrogens on female reproductive health. The literature search was performed on four electronic databases including Scopus, Science Direct, PubMed, and Google Scholar following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A total of 965 studies were screened but only 58 of them were found to be relevant and assessed for eligibility. Of these, 23 studies met the eligibility criteria while the remaining studies were excluded due to insufficiently described methods and lack of clear findings being reported. From the review, phytoestrogens may alter the development of reproductive organs, prolong the estrus cycle, induce the accumulation of fluid in the uterus, and inhibit ovulation. The concentration and exposure duration of phytoestrogens may have different effects on the reproductive organs. Thus, further studies are warranted on the toxicodynamic, toxicokinetic, mode of action, and mechanism of actions of phytoestrogens on the female reproductive system to establish recommendations regarding phytoestrogen supplement consumption for women.

Protective effect of phytoestrogens on nonalcoholic fatty liver disease in postmenopausal women.

Non-alcoholic fatty liver disease (NAFLD) is a progressive metabolic disease characterized by hepatic steatosis, inflammation, and fibrosis that seriously endangers global public health. Epidemiological studies have shown that the incidence of non-alcoholic fatty liver disease in postmenopausal women has significantly increased. Studies have shown that estrogen deficiency is the main reason for this situation, and supplementing estrogen has become a new direction for preventing the occurrence of postmenopausal fatty liver. However, although classical estrogen replacement therapy can reduce the incidence of postmenopausal NAFLD, it has the risk of increasing stroke and cardiovascular diseases, so it is not suitable for the treatment of postmenopausal NAFLD. More and more recent studies have provided evidence that phytoestrogens are a promising method for the treatment of postmenopausal NAFLD. However, the mechanism of phytoestrogens in preventing and treating postmenopausal NAFLD is still unclear. This paper summarizes the clinical and basic research evidence of phytoestrogens and reviews the potential therapeutic effects of phytoestrogens in postmenopausal NAFLD from six angles: enhancing lipid metabolism in liver and adipose tissue, enhancing glucose metabolism, reducing oxidative stress, reducing the inflammatory response, regulating intestinal flora, and blocking liver fibrosis (Graphical Abstract).

Multi-Anticancer Activities of Phytoestrogens in Human Osteosarcoma.

Phytoestrogens are plant-derived bioactive compounds with estrogen-like properties. Their potential health benefits, especially in cancer prevention and treatment, have been a subject of considerable research in the past decade. Phytoestrogens exert their effects, at least in part, through interactions with estrogen receptors (ERs), mimicking or inhibiting the actions of natural estrogens. Recently, there has been growing interest in exploring the impact of phytoestrogens on osteosarcoma (OS), a type of bone malignancy that primarily affects children and young adults and is currently presenting limited treatment options. Considering the critical role of the estrogen/ERs axis in bone development and growth, the modulation of ERs has emerged as a highly promising approach in the treatment of OS. This review provides an extensive overview of current literature on the effects of phytoestrogens on human OS models. It delves into the multiple mechanisms through which these molecules regulate the cell cycle, apoptosis, and key pathways implicated in the growth and progression of OS, including ER signaling. Moreover, potential interactions between phytoestrogens and conventional chemotherapy agents commonly used in OS treatment will be examined. Understanding the impact of these compounds in OS holds great promise for developing novel therapeutic approaches that can augment current OS treatment modalities.

Effect of Herbal Medicine on Bone Turnover Markers in Pre- and Peri/postmenopausal Women: An Overview of Meta-Analyses

Background: Osteoporosis is a chronic debilitating disease that poses a serious challenge to humanity. Osteoporosis and its related complications impose huge direct costs on the health system. Objectives: The purpose of this study was to critically evaluate the effects of soy isoflavones and phytoestrogens on bone turnover markers in pre- and peri/postmenopausal women. Methods: Three main databases [MEDLINE, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL)] were searched to explore published meta-analyses. The methodological quality was assessed by AMSTAR. Results: Four meta-analyses were included in this overview. Isoflavones and phytoestrogens significantly decreased urinary pyridinoline (Pyd). The subgroup analysis of Pyd indicated that isoflavones were more effective in overweight/obese individuals, and a dosage of &lt; 90 mg/day Deoxypyridinoline (Dpyd) had a desirable effect on phytoestrogens. However, the findings regarding the effect of isoflavones on Dpyd were controversial. The subgroup analysis of Pyd showed that isoflavones in the form of extract and tablet caused a significant decrease; nevertheless, soy foods with isoflavones and isolated soy protein failed to induce a significant drop. Isoflavones decreased Dpyd even during the intervention but were unable to induce a significant decrease. Moreover, although isoflavones considerably reduced Dpyd in postmenopausal women, it was non-significant in peri-menopausal women. The bone formation markers of bone-specific alkaline phosphatase, N-telopeptide, and osteocalcin were not significantly different between soy isoflavones and the control group. Osteoprotegerin was significantly higher, and C-telopeptide was significantly lower in women receiving isoflavones than in women in the control group. Conclusions: The current overview showed that isoflavones might decrease some urinary bone resorption markers. However, it had no significant effect on bone formation markers and influenced turnover markers in menopausal women.

Hepatotoxic effect of dietary phytoestrogens on juvenile cultured Russian sturgeon (Acipenser gueldenstaedtii)

In the last two decades, much controversy has grown over the use of soybean products in aquafeeds, especially for carnivorous fish like sturgeons. One point of discussion is the effect of soybean phytoestrogens on fish health. There are many aspects of phytoestrogen utilization in aquafeeds, therefore, the aim of this study is to verify if common legume phytoestrogens can affect juvenile cultured sturgeon erythrocyte and hepatocyte genotoxicity and cause liver pathology. Russian sturgeons were fed from 100 till 365 dph11Days post hutching. with daidzein, genistein, and coumestrol supplemented diets in concentrations: 10, 0.05 and 0.001 g kg−1 of feed, respectively. The SCGE22Single Cell Gel Electrophoresis (comet assay). method combined with qPCR of three genes involved in DNA repair and genome maintenance, namely cyp1a1, gaad45a and p53 were analyzed. The results were compared with histopathological evaluation of liver tissue. In fish fed with coumestrol supplemented diet, DNA strand damage was the highest in both erythrocytes and hepatocytes, however, simultaneously the lowest level of oxidative DNA damage was found. Additionally, slightly elevated expression of the p53 gene was observed along with a decreased number of apoptotic hepatocytes, which suggests that low concentration of coumestrol may support DNA repair mechanisms in the liver. Although, daidzein showed a preventive effect only against fibrosis. Isoflavones did not show a significant effect on DNA damage in studied cells. Genistein was found to increase macro- and microvesicular steatosis, portal hepatitis and fibrosis, indicating its negative role in the development of liver injuries. Daidzein alleviated some sturgeon liver damage, especially macrovesicular steatosis and interface hepatitis. However, it increased hepatocyte apoptosis, which may suggest daidzein potentially inducing liver injury, though not manifested by other histopathological lesions. Therefore, it can be concluded that at given concentrations, the tested phytoestrogens did not show clearly hepatoprotective effect in sturgeons.