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Molecules (Basel, Switzerland) Mar 2019Phytoestrogens are naturally occurring nonsteroidal phenolic plant compounds that, due to their molecular structure and size, resemble vertebrate steroids estrogens.... (Review)
Review
Phytoestrogens are naturally occurring nonsteroidal phenolic plant compounds that, due to their molecular structure and size, resemble vertebrate steroids estrogens. This review is focused on plant flavonoids isoflavones, which are ranked among the most estrogenic compounds. The main dietary sources of isoflavones for humans are soybean and soybean products, which contain mainly daidzein and genistein. When they are consumed, they exert estrogenic and/or antiestrogenic effects. Isoflavones are considered chemoprotective and can be used as an alternative therapy for a wide range of hormonal disorders, including several cancer types, namely breast cancer and prostate cancer, cardiovascular diseases, osteoporosis, or menopausal symptoms. On the other hand, isoflavones may also be considered endocrine disruptors with possible negative influences on the state of health in a certain part of the population or on the environment. This review deals with isoflavone classification, structure, and occurrence, with their metabolism, biological, and health effects in humans and animals, and with their utilization and potential risks.
Topics: Animals; Equol; Genistein; Humans; Isoflavones; Phytoestrogens
PubMed: 30893792
DOI: 10.3390/molecules24061076 -
Cell May 2022Epidemiological studies reveal that marijuana increases the risk of cardiovascular disease (CVD); however, little is known about the mechanism. Δ-tetrahydrocannabinol...
Epidemiological studies reveal that marijuana increases the risk of cardiovascular disease (CVD); however, little is known about the mechanism. Δ-tetrahydrocannabinol (Δ-THC), the psychoactive component of marijuana, binds to cannabinoid receptor 1 (CB1/CNR1) in the vasculature and is implicated in CVD. A UK Biobank analysis found that cannabis was an risk factor for CVD. We found that marijuana smoking activated inflammatory cytokines implicated in CVD. In silico virtual screening identified genistein, a soybean isoflavone, as a putative CB1 antagonist. Human-induced pluripotent stem cell-derived endothelial cells were used to model Δ-THC-induced inflammation and oxidative stress via NF-κB signaling. Knockdown of the CB1 receptor with siRNA, CRISPR interference, and genistein attenuated the effects of Δ-THC. In mice, genistein blocked Δ-THC-induced endothelial dysfunction in wire myograph, reduced atherosclerotic plaque, and had minimal penetration of the central nervous system. Genistein is a CB1 antagonist that attenuates Δ-THC-induced atherosclerosis.
Topics: Analgesics; Animals; Cannabinoid Receptor Agonists; Cannabis; Cardiovascular Diseases; Dronabinol; Endothelial Cells; Genistein; Hallucinogens; Inflammation; Mice; Receptor, Cannabinoid, CB1; Receptors, Cannabinoid
PubMed: 35489334
DOI: 10.1016/j.cell.2022.04.005 -
Oxidative Medicine and Cellular... 2021Genistein is an isoflavone first isolated from the brooming plant Dyer's L. and is widely distributed in the Fabaceae family. As an isoflavone, mammalian genistein... (Review)
Review
Genistein is an isoflavone first isolated from the brooming plant Dyer's L. and is widely distributed in the Fabaceae family. As an isoflavone, mammalian genistein exerts estrogen-like functions. Several biological effects of genistein have been reported in preclinical studies, such as the antioxidant, anti-inflammatory, antibacterial, and antiviral activities, the effects of angiogenesis and estrogen, and the pharmacological activities on diabetes and lipid metabolism. The purpose of this review is to provide up-to-date evidence of preclinical pharmacological activities with mechanisms of action, bioavailability, and clinical evidence of genistein. The literature was researched using the most important keyword "genistein" from the PubMed, Science, and Google Scholar databases, and the taxonomy was validated using The Plant List. Data were also collected from specialized books and other online resources. The main positive effects of genistein refer to the protection against cardiovascular diseases and to the decrease of the incidence of some types of cancer, especially breast cancer. Although the mechanism of protection against cancer involves several aspects of genistein metabolism, the researchers attribute this effect to the similarity between the structure of soy genistein and that of estrogen. This structural similarity allows genistein to displace estrogen from cellular receptors, thus blocking their hormonal activity. The pharmacological activities resulting from the experimental studies of this review support the traditional uses of genistein, but in the future, further investigations are needed on the efficacy, safety, and use of nanotechnologies to increase bioavailability and therapeutic efficacy.
Topics: Anticarcinogenic Agents; Genistein; Humans
PubMed: 34336089
DOI: 10.1155/2021/3268136 -
Redox Biology May 2023Senescence of bone marrow mesenchymal stem cells (BMMSCs) induced by chronic oxidative stress is an important factor contributes to the postmenopausal osteoporosis...
Senescence of bone marrow mesenchymal stem cells (BMMSCs) induced by chronic oxidative stress is an important factor contributes to the postmenopausal osteoporosis (PMOP). Mitochondrial quality control takes a pivotal role in regulating oxidative stress and cell senescence. Genistein is a major isoflavone in soy products, which is best known for its ability to inhibit bone loss in both postmenopausal women and ovariectomized (OVX) rodents. Here we show that OVX-BMMSCs displayed premature senescence, elevated reactive oxygen species (ROS) level and mitochondria dysfunction, while genistein rescued these phenotypes. Using network pharmacology and molecular docking, we identified estrogen-related receptor α (ERRα) as the potential target of genistein. Knockdown of ERRα greatly abolished the anti-senescence effect of genistein on OVX-BMMSCs. Further, the mitochondrial biogenesis and mitophagy induced by genistein were inhibited by ERRα knockdown in OVX-BMMSCs. In vivo, genistein inhibited trabecular bone loss and p16 expression, upregulated sirtuin 3 (SIRT3) and peroxisome proliferator-activated receptor gamma coactivator one alpha (PGC1α) expression in the trabecular bone area of proximal tibia in OVX rats. Together, this study revealed that genistein ameliorates senescence of OVX-BMMSCs through ERRα-mediated mitochondrial biogenesis and mitophagy, which provided a molecular basis for advancement and development of therapeutic strategies against PMOP.
Topics: Animals; Female; Rats; Cellular Senescence; Genistein; Mesenchymal Stem Cells; Mitophagy; Molecular Docking Simulation; Organelle Biogenesis; Ovariectomy; ERRalpha Estrogen-Related Receptor
PubMed: 36871183
DOI: 10.1016/j.redox.2023.102649 -
Pharmacological Research Feb 2023Age-related gastrointestinal decline contributes to whole-organism frailty and mortality. Genistein is known to have beneficial effects on age-related diseases, but its...
Age-related gastrointestinal decline contributes to whole-organism frailty and mortality. Genistein is known to have beneficial effects on age-related diseases, but its precise role in homeostasis of the aging gut remains to be elucidated. Here, wild-type aging mice and Zmpste24 progeroid mice were used to investigate the role of genistein in lifespan and homeostasis of the aging gut in mammals. A series of longitudinal, clinically relevant measurements were performed to evaluate the effect of genistein on healthspan. It was found that dietary genistein promoted a healthier and longer life and was associated with a decrease in the levels of systemic inflammatory cytokines in aging mice. Furthermore, dietary genistein ameliorated gut dysfunctions, such as intestinal inflammation, leaky gut, and impaired epithelial regeneration. A distinct genistein-mediated alteration in gut microbiota was observed by increasing Lachnospira abundance and short-chain fatty acid (SCFA) production. Further fecal microbiota transplantation and dirty cage sharing experiments indicated that the gut microbiota from genistein-fed mice rejuvenated the aging gut and extended the lifespan of progeroid mice. It was demonstrated that genistein-associated SCFAs alleviated tumor necrosis factor alpha-induced intestinal organoid damage. Moreover, genistein-associated propionate promoted regulatory T cell-derived interleukin 10 production, which alleviated macrophage-derived inflammation. This study provided the first data, to the authors' knowledge, indicating that dietary genistein modulates homeostasis in the aging gut and extends the healthspan and lifespan of aging mammals. Moreover, the existence of a link between genistein and the gut microbiota provides a rationale for dietary interventions against age-associated frailty.
Topics: Mice; Animals; Longevity; Genistein; Frailty; Fatty Acids, Volatile; Aging; Inflammation; Gastrointestinal Microbiome; Homeostasis; Mice, Inbred C57BL; Mammals
PubMed: 36693599
DOI: 10.1016/j.phrs.2023.106676 -
Mechanisms of Ageing and Development Jun 2022Geroprotection is defined as protection from the adverse effects of aging. The need for geroprotection implies changes towards individually tailored interventions that... (Review)
Review
Geroprotection is defined as protection from the adverse effects of aging. The need for geroprotection implies changes towards individually tailored interventions that preserve an individual's independence, physical function, and cognition. Genistein, a phytoestrogen obtained from soya, has been reported to have beneficial properties on age-related diseases such as neurodegenerative and cardiovascular diseases or cancer. Indeed, genistein is a multimodal agent: it acts as a cancer protective agent, promoting apoptosis and cell cycle arrest, and inhibiting angiogenesis and metastasis, but it also acts as an antioxidant, anti-inflammatory, and anti-amyloid-β and autophagy promoter. Altogether, these properties make genistein a possible treatment for the specific aspects of age-related diseases such as hypertension, metabolic diseases, Alzheimer's disease, and osteoporosis.
Topics: Amyloid beta-Peptides; Genistein; Geroscience; Humans; Neoplasms; Phytoestrogens
PubMed: 35307412
DOI: 10.1016/j.mad.2022.111665 -
Advances in Nutrition (Bethesda, Md.) Jul 2015Primary prevention through lifestyle interventions is a cost-effective alternative for preventing a large burden of chronic and degenerative diseases, including cancer,... (Review)
Review
Primary prevention through lifestyle interventions is a cost-effective alternative for preventing a large burden of chronic and degenerative diseases, including cancer, which is one of the leading causes of morbidity and mortality worldwide. In the past decade, epidemiologic and preclinical evidence suggested that polyphenolic phytochemicals present in many plant foods possess chemopreventive properties against several cancer forms. Thus, there has been increasing interest in the potential cancer chemopreventive agents obtained from natural sources, such as polyphenols, that may represent a new, affordable approach to curb the increasing burden of cancer throughout the world. Several epidemiologic studies showed a relation between a soy-rich diet and cancer prevention, which was attributed to the presence of a phenolic compound, genistein, present in soy-based foods. Genistein acts as a chemotherapeutic agent against different types of cancer, mainly by altering apoptosis, the cell cycle, and angiogenesis and inhibiting metastasis. Targeting caspases, B cell lymphoma 2 (Bcl-2)-associated X protein (Bax), Bcl-2, kinesin-like protein 20A (KIF20A), extracellular signal-regulated kinase 1/2 (ERK1/2), nuclear transcription factor κB (NF-κB), mitogen-activated protein kinase (MAPK), inhibitor of NF-κB (IκB), Wingless and integration 1 β-catenin (Wnt/β-catenin), and phosphoinositide 3 kinase/Akt (PI3K/Akt) signaling pathways may act as the molecular mechanisms of the anticancer, therapeutic effects of genistein. Genistein also shows synergistic behavior with well-known anticancer drugs, such as adriamycin, docetaxel, and tamoxifen, suggesting a potential role in combination therapy. This review critically analyzes the available literature on the therapeutic role of genistein on different types of cancer, focusing on its chemical features, plant food sources, bioavailability, and safety.
Topics: Animals; Antineoplastic Agents; Apoptosis; Biological Availability; Caspase Inhibitors; Caspases; Cell Cycle; Chemoprevention; Drug Synergism; Fabaceae; Female; Genistein; Humans; Male; Mice; Neoplasm Metastasis; Neoplasms; Neovascularization, Pathologic; Phytochemicals; Soy Foods; Glycine max
PubMed: 26178025
DOI: 10.3945/an.114.008052 -
Nutrients Aug 2021Advanced research in recent years has revealed the important role of nutrients in the protection of women's health and in the prevention of women's diseases. Genistein... (Review)
Review
Advanced research in recent years has revealed the important role of nutrients in the protection of women's health and in the prevention of women's diseases. Genistein is a phytoestrogen that belongs to a class of compounds known as isoflavones, which structurally resemble endogenous estrogen. Genistein is most often consumed by humans via soybeans or soya products and is, as an auxiliary medicinal, used to treat women's diseases. In this review, we focused on analyzing the geographic distribution of soybean and soya product consumption, global serum concentrations of genistein, and its metabolism and bioactivity. We also explored genistein's dual effects in women's health through gathering, evaluating, and summarizing evidence from current in vivo and in vitro studies, clinical observations, and epidemiological surveys. The dose-dependent effects of genistein, especially when considering its metabolites and factors that vary by individuals, indicate that consumption of genistein may contribute to beneficial effects in women's health and disease prevention and treatment. However, consumption and exposure levels are nuanced because adverse effects have been observed at lower concentrations in in vitro models. Therefore, this points to the duplicity of genistein as a possible therapeutic agent in some instances and as an endocrine disruptor in others.
Topics: Endocrine Disruptors; Female; Genistein; Humans; Phytoestrogens; Women's Health
PubMed: 34578926
DOI: 10.3390/nu13093048 -
Frontiers in Endocrinology 2023Genistein (GN) has been highly recommended for its medicinal properties like anticancer, antidiabetic, antihyperlipidemic, antiviral, and antioxidant activities among... (Review)
Review
Genistein (GN) has been highly recommended for its medicinal properties like anticancer, antidiabetic, antihyperlipidemic, antiviral, and antioxidant activities among others. Recently, scientists realized that Genistein is an endocrine disruptor. It is an obesogen that interferes with the endocrine system causing obesity through many mechanisms like inducing adipocyte differentiation, lipid accumulation, and transformation of some stem cells into adipocytes (bone marrow mesenchymal stem cells for example) . Animal studies show that GN upregulates genes associated with adipogenesis like CCAAT/enhancer binding protein alpha (Cebpα), CCAAT/enhancer binding protein beta (Cebpβ), and PPARγ. studies reveal a strong binding affinity for estrogen receptors. All these findings were contingent on concentration and tissues. It is beyond dispute that obesity is one of the most frustrating medical conditions under the sun. The pathophysiology of this disease was first attributed to a high-calorie diet and lack of physical activity. However, studies proved that these two factors are not enough to account for obesity in both children and adults. This mini review highlights how Genistein interaction with the peroxisome proliferator-activated receptor gamma protein can cause obesity.
Topics: Animals; Child; Humans; Genistein; Cell Differentiation; Adipogenesis; Obesity
PubMed: 38098865
DOI: 10.3389/fendo.2023.1308341 -
American Journal of Physiology.... Sep 2022Diabetes is the eighth leading cause of death in the world and the prevalence is rising in low-income countries. Cardiovascular diseases are the leading cause of death... (Review)
Review
Diabetes is the eighth leading cause of death in the world and the prevalence is rising in low-income countries. Cardiovascular diseases are the leading cause of death worldwide, especially for individuals with diabetes. Although medications exist to treat symptoms of diabetes, lack of availability and high costs may deter their use by individuals with low incomes as well as those in low-income nations. Therefore, this systematic review was performed to determine whether genistein, a phytoestrogen found in soy products, could provide therapeutic benefits for individuals with diabetes. We searched PubMed and SCOPUS using the terms "genistein," "diabetes," and "glucose" and identified 33 peer-reviewed articles that met our inclusion criteria. In general, preclinical studies demonstrated that genistein decreases body weight and circulating glucose and triglycerides concentrations, whereas increasing insulin levels and insulin sensitivity. Genistein also delayed the onset of type 1 and type 2 diabetes. In contrast, clinical studies utilizing genistein generally reported no significant relationship between genistein and body mass, circulating glucose, glycated hemoglobin (A1C) concentrations, or onset of type 1 diabetes. However, genistein was found to improve insulin sensitivity and serum triglyceride concentrations and delayed the onset of type 2 diabetes. In summary, preclinical and clinical studies suggest that genistein may help delay the onset of type 2 diabetes and improve several symptoms associated with the disease. Although additional research is required to confirm these findings, the results highlighted in this review provide some evidence that genistein may offer a natural approach to mitigating some of the complications associated with diabetes.
Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Genistein; Glycated Hemoglobin; Humans; Insulin Resistance
PubMed: 35816719
DOI: 10.1152/ajpregu.00236.2021