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•Phytoestrogens and their analogs and derivatives possess breast cancer preventive properties.•Phytoestrogens, analogs and derivatives exert in vitro anticancer activities by ...modulating various molecular targets.•Most analogs and derivatives exert more effective anticancer activities than their corresponding parent compounds.
Breast cancer is one of the leading causes of cancer-related morbidity and mortality among women worldwide. Phytoestrogens, plant-derived polyphenols that structurally and functionally mimic 17β-estradiol, the mammalian estrogen hormone, are known to modulate multiple molecular targets in breast cancer cells. The structural and chemical similarities to estradiol enable phytoestrogens to exert estrogenic or antiestrogenic activities by binding to the estrogen receptors. Although phytoestrogens have low affinity for estrogen receptors, they are able to compete with 17β-estradiol for the ligand-binding domain of the receptors. Phytoestrogens trigger epigenomic effects that could be beneficial in breast cancer prevention and/or treatment. Few studies have focused on the cytotoxic and structure-activity relationships of phytoestrogen analogs and derivatives with more effective anticancer properties than their corresponding parent compounds. Phytoestrogens and their analogs and derivatives bind to estrogen receptors, with a preferential affinity for ERβ, and inhibit the growth promoting activity of ERα. These bioactive compounds also exert growth inhibitory effects through various cell signaling pathways. At the level of cell cycle, they inhibit the expression of oncogenic cyclin D1, increase the expression of cyclin-dependent kinase inhibitors (p21, p27, and p57) and tumor suppressor genes (APC, ATM, PTEN, SERPINB5). Phytoestrogens and their analogs and derivatives mediate their effects on breast cancer by inhibiting estrogen synthesis and metabolism, as well as exerting antiangiogenic, antimetastatic, and epigenetic effects. Furthermore, these bioactive compounds reverse multi-drug resistance. This review offers a comprehensive summary of current literature and future perspectives on the in vitro molecular mechanisms of the anticancer activities of phytoestrogens and their analogs and derivatives on breast cancer.
Neurodegenerative disorders are heterogeneous, debilitating, and incurable groups of brain disorders that have common features including progressive degeneration of the structure and function of the ...nervous system. Phytoestogenic‐isoflavones have been identified as active compounds that can modulate different molecular signaling pathways related to the nervous system. The main aim is to shed the light on the molecular mechanisms followed by phytoestrogen‐isoflavones profound in the Trifolium pratense and discuss the latest pharmacological findings in the treatment of neurodegenerative disorders. Data were collected using different databases. The search terms used included “Phytoestrogens,” “Isoflavones,” “neurodegenerative disorders,” “Neuronal plasticity,” etc., and combinations of these keywords. As a result, this review article mainly demonstrates the potential neuroprotective properties of phystoestrogen‐isoflavones present in the Trifolium pratense (Red clover), particularly in neurodegenerative disorders. Phytochemical studies have shown that Trifolium pratense mainly includes more than 30 isoflavone compounds. Among them, phytoestrogen‐isoflavones, such as biochanin A, daidzein, formononetin, genistein (Gen), etc.,are characterized by potent neuroprotective properties against different neurodegenerative disorders. There are preclinical and clinical scientific evidence on their mechanisms of action involve molecular interaction with estrogenic receptors, anti‐inflammatory, anti‐oxidative, antiapoptotic, autophagic inducing, and so on. phytoestrogen‐isoflavones are the major bioactive components in the Trifolium pratense that exhibit therapeutic efficacy in the case of neurodegenerative disorders. This review provides detailed molecular mechanisms targeted by phytoestrogen‐isoflavones and experimental key findings for the clinical use of prescriptions containing Trifolium pratense‐derived isoflavones for the treatment of neurodegenerative disorders.
Essential phytoestrogen‐isoflavones derived from Trifolium Pratense and their neuroprotective mechanisms in context of neurodegenerative disorders.
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Exposure to naturally derived estrogen receptor activators, such as the phytoestrogen genistein, can occur at physiologically relevant concentrations in the human diet. Soy-based ...infant formulas are of particular concern because infants consuming these products have serum genistein levels almost 20 times greater than those seen in vegetarian adults. Comparable exposures in animal studies have adverse physiologic effects. The timing of exposure is particularly concerning because infants undergo a steroid hormone-sensitive period termed “minipuberty” during which estrogenic chemical exposure may alter normal reproductive tissue patterning and function. The delay between genistein exposure and reproductive outcomes poses a unique challenge to collecting epidemiological data. In 2010, the U.S. National Toxicology Program monograph on the safety of the use of soy formula stated that the use of soy-based infant formula posed minimal concern and emphasized a lack of data from human subjects. Since then, several new human and animal studies have advanced our epidemiological and mechanistic understanding of the risks and benefits of phytoestrogen exposure. Here we aim to identify clinically relevant findings regarding phytoestrogen exposure and female reproductive outcomes from the past 10 years, with a focus on the phytoestrogen genistein, and explore the implications of these findings for soy infant formula recommendations. Research presented in this review will inform clinical practice and dietary recommendations for infants based on evidence from both clinical epidemiology and basic research advances in endocrinology and developmental biology from mechanistic in vitro and animal studies.
Epidemiological studies suggest that Mediterranean diets rich in resveratrol are associated with reduced risk of coronary artery disease. However, the mechanisms by which resveratrol exerts its ...cardioprotective effects are not completely understood. Because TNF-α-induced endothelial activation and vascular inflammation play a critical role in vascular aging and atherogenesis, we evaluated whether resveratrol inhibits TNF-α-induced signal transduction in human coronary arterial endothelial cells (HCAECs). We found that TNF-α significantly increased adhesiveness of the monocytic THP-1 cells to HCAECs, an effect that could be inhibited by pretreatment with resveratrol and the NF-κB inhibitor pyrrolidine dithiocarbamate. Previously, we found that TNF-α activates NAD(P)H oxidases, and our recent data showed that TNF-α-induced endothelial activation was prevented by the NAD(P)H oxidase inhibitor apocynin or catalase plus SOD. Resveratrol also inhibited H
2
O
2
-induced monocyte adhesiveness. Using a reporter gene assay, we found that, in HCAECs, TNF-α significantly increased NF-κB activity, which could be inhibited by resveratrol (>50% inhibition at 10
−6
mol/l) and pyrrolidine dithiocarbamate. Resveratrol also inhibited TNF-α-induced, NF-κB-driven luciferase expression in rat aortas electroporated with the reporter gene construct. In TNF-α-treated HCAECs, resveratrol (in the submicromolar range) significantly attenuated expression of NF-κB-dependent inflammatory markers inducible nitric oxide synthase, IL-6, bone morphogenetic protein-2, ICAM-1, and VCAM. Thus resveratrol at nutritionally relevant concentrations inhibits TNF-α-induced NF-κB activation and inflammatory gene expression and attenuates monocyte adhesiveness to HCAECs. We propose that these anti-inflammatory actions of resveratrol are responsible, at least in part, for its cardioprotective effects.
•Naturally occurring oestrogens and progesterone are present in human milk (HM).•HM oestrogens and progesterone are influenced by many factors.•Impacts of infant intake of HM oestrogens and ...progesterone are yet to be assessed.
Human milk (HM) is a complex biological system that contains a wide range of bioactive components including oestrogens and progesterone. Whilst maternal oestrogens and progesterone concentrations drop rapidly after birth, they remain detectable in HM across lactation. Phytoestrogens and mycoestrogens, which are produced by plants and fungi, are also present in HM and can interact with oestrogen receptors to interfere with normal hormone functions. Despite the potential impact of HM oestrogens and progesterone on the infant, limited research has addressed their impact on the growth and health of breastfed infants. Furthermore, it is important to comprehensively understand the factors that contribute to these hormone levels in HM, in order to establish effective intervention strategies. In this review, we have summarized the concentrations of naturally occurring oestrogens and progesterone in HM from both endogenous and exogenous sources and discussed both maternal factors impacting HM levels and relationships with infant growth.
Introduction: Menopause is associated with increased bone resorption and decreased bone mineral density (BMD). Phytoestrogens are believed to prevent bone loss. This study reviewed relevant ...randomized, controlled trials to determine the effects of phytoestrogens on BMD in postmenopausal women.
Methods: In order to perform this systematic review, PubMed, Science Direct, Scopus, Cochrane Library, ISI Web of Knowledge, and ProQuest databases were searched for articles published during 2005-2016. The main keywords used during the searches were "phytoestrogen" and "bone mineral density" and "menopause". The Cochrane Risk of Bias Assessment Tool was used to evaluate the quality of the selected studies and to assess the risk of bias.
Results: A total of 23 eligible studies were included in this systematic review. Most selected studies used a double-blind, placebo-controlled design. In total, 3494 participants were enrolled in the selected trials. Different types of soy isoflavone extracts, including genistein extracts (either alone or in combination with daidzein), dietary products containing different amounts of phytoestrogens, and red clover extracts were used in the designed interventions. The duration of the interventions ranged from 7 weeks to 3 years. In most studies, the primary outcome was the efficacy of the designed intervention which was assessed through measuring whole body or regional BMD or bone mineral content, T-scores, and biomarkers of bone metabolism.
Conclusions: Isoflavones probably have beneficial effects on bone health in menopausal women. Nevertheless, there were controversial reports about changes in BMD. Supplementation with a phytoestrogen can probably prevent the reduction in BMD and maintain a healthy bone structure during menopause.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The seed of
Psoralea corylifolia L. (PCL), a well-known traditional Chinese medicine, has been applied as a tonic or an aphrodisiac agent and commonly used as a remedy for bone fracture, osteomalacia ...and osteoporosis in China. In our study, the estrogen receptor subtype-selective activities of the extracts and compounds derived from PCL were analyzed using the HeLa cell assay. The different fractions including petroleum ether, CH
2Cl
2 and EtOAc fractions of the EtOH extract of PCL showed significant activity in activating either ERα or ERβ whereas the
n-BuOH fraction showed no estrogenic activity. Further chromatographic purification of the active fractions yielded seven compounds including the two coumarins isopsoralen and psoralen, the four flavonoids isobavachalcone, bavachin, corylifol A and neobavaisoflavone, and the meroterpene phenol, bakuchiol. In reporter gene assay, the two coumarins (10
−8-10
−5
M) acted as ERα-selective agonists while the other compounds (10
−9-10
−6
M) activated both ERα and ERβ. The estrogenic activities of all compounds could be completely suppressed by the pure estrogen antagonist, ICI 182,780, suggesting that the compounds exert their activities through ER. Only psoralen and isopsoralen as ERα agonists promoted MCF-7 cell proliferation significantly. Although all the compounds have estrogenic activity, they may exert different biological effects. In conclusion, both ER subtype-selective and nonselective activities in compounds derived from PCL suggested that PCL could be a new source for selective estrogen-receptor modulators.
•One principal regulator of circulating estrogens is the gut microbiome.•Disruption in the gut microbiome results in decreased circulating estrogens.•Alterations in the estrobolome can drive ...estrogen-mediated pathologies.•Bariatric surgery, fecal-microbiome transplant and metformin alter gut microbiota composition.•Interventions that alter gut microbiome diversity impact estrogen-mediated disease.
Low levels of gonadal circulating estrogen observed in post-menopausal women can adversely impact a diverse range of physiological factors, with clinical implications for brain cognition, gut health, the female reproductive tract and other aspects of women’s health. One of the principal regulators of circulating estrogens is the gut microbiome. This review aims to shed light on the role of the gut microbiota in estrogen-modulated disease. The gut microbiota regulates estrogens through secretion of β-glucuronidase, an enzyme that deconjugates estrogens into their active forms. When this process is impaired through dysbiosis of gut microbiota, characterized by lower microbial diversity, the decrease in deconjugation results in a reduction of circulating estrogens. The alteration in circulating estrogens may contribute to the development of conditions discussed herein: obesity, metabolic syndrome, cancer, endometrial hyperplasia, endometriosis, polycystic ovary syndrome, fertility, cardiovascular disease (CVD) and cognitive function. The bi-directional relationship between the metabolic profile (including estrogen levels) and gut microbiota in estrogen-driven disease will also be discussed. Promising therapeutic interventions manipulating the gut microbiome and the metabolic profile of estrogen-driven disease, such as bariatric surgery and metformin, will be detailed. Modulation of the microbiome composition subsequently impacts the metabolic profile, and vice versa, and has been shown to alleviate many of the estrogen-modulated disease states. Last, we highlight promising research interventions in the field, such as dietary therapeutics, and discuss areas that provide exciting unexplored topics of study.
Introduction: Phytoestrogen containing foods are known useful in controlling menopause symptom. Researches revealed that these foods can be useful for the health of menopausal women. Considering the ...importance of non-pharmacological treatments in reducing menopausal symptoms and confirming the effectiveness of phytoestrogen consumption in reducing these symptoms, this study was conducted to investigate the amount of phytoestrogen consumption and its relationship with menopausal symptoms.Methods: This cross-sectional study was performed in 2022 on 130 middle-aged (45 to 55 years old) women living in Jahrom, Iran. Tools used in this study included a demographic questionnaire, a menopause rating scale, knowledge and attitude regarding phytoestrogen-containing foods and a 3-day food record questionnaire. Data were analyzed using SPSS software (version 24) and Pearson correlation coefficient. P<0.05 was considered statistically significant.Results: The mean amount of phytoestrogen consumed daily by the participants was 72.92±33.36 mg. Pearson correlation analyses indicated that the total amount of phytoestrogens consumed had an inverse and significant correlation with the psychological symptoms of menopause (p=.01, r=-0.190), but no significant relationship was found with the physical, urogenital, and total symptoms of menopause with amount of phytoestrogens consumed (p=0.11).Conclusion: The consumption of phytoestrogens to some extent leads to a reduction of mental symptoms in menopausal women, but they have no effect on physical symptoms.
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