Search Results (372)

Menopause is characterized by a decline in estrogen levels, leading to symptoms such as vasomotor instability, osteoporosis, and increased cardiovascular and cognitive risk. Hormone replacement therapy (HRT) remains the gold standard for managing menopausal symptoms; however, concerns regarding its long-term safety, including elevated risks of cancer and cardiovascular events, have prompted interest in alternative therapies. Phytoestrogens, particularly the isoflavones daidzein and genistein, are plant-derived compounds structurally similar to 17β-estradiol (E2) and capable of binding estrogen receptors. Found abundantly in soybeans and red clover, these compounds exhibit selective estrogen receptor modulator (SERM)-like activity, favoring ERβ over ERα, which underlies their tissue-specific effects. In vitro, in silico, and in vivo studies demonstrate their ability to modulate estrogenic pathways, inhibit oxidative stress, and influence reproductive and neurological function. Clinical trials show that daidzein and genistein, especially in equol-producing individuals, can reduce vasomotor symptoms such as hot flashes and night sweats. While results across studies vary, consistent findings support their safety and modest efficacy, particularly for women unable or unwilling to use HRT. Pharmacokinetic studies reveal moderate bioavailability and interindividual variability due to gut microbiota metabolism. At dietary levels, these compounds are generally safe, although high-dose supplementation is discouraged in individuals with hormone-sensitive cancers. Emerging evidence suggests lifelong consumption of soy-based foods may reduce cancer risk. In conclusion, daidzein and genistein represent promising, well-tolerated natural alternatives to conventional HRT, offering symptom relief and additional health benefits. Further research is warranted to optimize dosing, improve clinical outcomes, and clarify long-term safety in diverse populations, particularly with genetic variations in isoflavone metabolism. Full article

Estrogen plays some important roles in many physiological processes in animals. This hormone is used as a type of medication for humans and animals, including fish, but is associated with serious side effects and environmental persistence, which has led to a growing interest in phytoestrogens as an alternative. Phytoestrogens are compounds derived from plants that are structurally similar to estrogen and may exhibit similar behavior in the body. To date, no studies have investigated the activity of phytoestrogens in relation to the maturation of eels. In the present study, we investigated the effects of ten different plant extracts on vitellogenin (vtg) and estrogen receptor (esr1, esr2) gene expression in eel hepatocytes. As a result, Schisandra and Astragalus extracts induced higher levels of vtg mRNA expression compared to the other extracts. However, increased esr mRNA expression was observed only in the Schisandra and soybean extract-treated groups. The phytoestrogens known to be present in Schisandra and Astragalus were analyzed using HPLC. Schizandrin, gomisin A, and gomisin N were detected in Schisandra extract, and calycosin and formononetin were detected in Astragalus extract. We then examined whether these phytoestrogens could induce vtg mRNA expression in eel hepatocytes. As a result, gomisin N and formononetin significantly induced vtg mRNA expression. In conclusion, among the 10 plant extracts treated in this study, Schisandra and Astragalus extracts induced estrogenic activity in eel hepatocytes. These extracts were found to contain phytoestrogens, with gomisin N and formononetin identified as the primary active components responsible for the observed estrogenic activity in eel hepatocytes. Full article

Marantodes pumilum (MP) is one of the traditional plants to which various medicinal properties are attributed. Studies on the medicinal properties of MP and its characteristics are becoming more extensive and are attracting more and more attention. In this review, the findings on the pharmacological properties of MP have been summarised and analysed. The results show that in addition to its phytoestrogenic effects on the female reproductive system, MP also has bone-remodelling properties, anti-obesity, anti-cancer, anti-gout, antimicrobial, anti-inflammatory and wound-healing effects, as well as effects on the cardiovascular system. These findings show that MP has great potential for the prevention and complementary treatment of various diseases. However, further research is needed to explore its full clinical potential. Full article

Aglycone-type soy isoflavones, recognized for their bioactive phytoestrogen properties, face industrial limitations due to their low natural abundance and inefficient conversion. This study optimized a multi-enzyme synergistic catalysis system using soybean sprout powder, achieving high conversion rates and purity through response surface methodology. The optimal enzyme system comprised β-glucosidase (25 U/mL), cellulase (200 U/mL), hemicellulase (400 U/mL), and β-galactosidase (900 U/mL) at pH 5.0, 50 °C, and 3.2 h. This system yielded an aglycone conversion rate of 92% and glycoside hydrolysis rate of 97%, outperforming single-enzyme approaches. Upon post-purification with AB-8 macroporous resin, the product reached a purity of 58.1 ± 0.54% and exhibited strong antioxidant activity, with DPPH and ABTS radical scavenging rates of 81.01 ± 0.78% and 71.37 ± 1.01%, respectively. In a zebrafish central nervous system injury model induced by mycophenolate mofetil, the 500 μg/mL sample group significantly reduced neural apoptosis fluorescence intensity compared to controls (p < 0.05), achieving a neuroprotective rate of 76.58%, which was similar to the effect of L-reducing glutathione. This study offers an efficient, cost-effective enzymatic strategy for producing aglycone soy isoflavones, highlighting their potential in functional foods and neuroprotective applications. Full article

Rye (Secale cereale L.), a cereal with valuable agronomic and nutritional benefits, contributes to sustainable agriculture, especially in areas where more demanding crops cannot be cultivated due to the poor agronomic value of soil. This review explores rye grain quality optimization strategies through production techniques. The quality and yield of grain are under the significant impact of agronomic factors, such as variety selection, crop rotation, soil tillage, fertilization, sowing practices, chemical protection, and harvest timing. It is also under the strong influence of the chosen farm’s management strategy, like organic or conventional farming system. This review emphasizes its diverse potential utilization routes, and the importance of bioactive compounds, dietary fibers, phenolic acids, phytoestrogens, and benzoxazinoids that enhance its value as a functional food. Cereal grain with quality issues cannot be used as food for humans, however, it can still be utilized alternatively as a renewable biofuel. This review showed rye grain to have a potential to contribute to sustainable agriculture and at the same time build farms’ resilience through possible alternative utilization strategies. It can serve as both a food source and a sustainable biofuel, offering a dual-purpose solution within the circular bioeconomy. Full article

The Fabaceae family is known for the presence of isoflavones—phytoestrogens with potential chemopreventive effects against hormone-dependent cancers. This study aimed to optimize isoflavones extraction using a fractional factorial design and to quantitatively and qualitatively analyze 32 Fabaceae species native to Polish flora by HPLC-UV-VIS to indicate new, rich plant sources of isoflavones. The optimal extraction method was a 60 min reflux with 50% methanol and a plant material-to-solvent ratio of 1:125. The highest isoflavone levels were found in Trifolium medium (26.70 mg/g d.m.), Genista tinctoria (19.65 mg/g d.m.), and Trifolium pratense (12.56 mg/g d.m.). The obtained extracts were further evaluated for cytotoxic and antiproliferative activity against MCF7 and MDA-MB-231 human breast cancer cells. Genista tinctoria showed the highest cytotoxicity against MCF7, while Cytisus scoparius and Ononis arvensis were most effective against MDA-MB-231 at a dose of 500 µg/mL. The extracts were also characterized by varied, potent antioxidant properties, important in chemoprevention. A strong correlation was observed between isoflavone content and cytotoxic and antiproliferative activity exclusively in the estrogen receptor-positive MCF7 cell line. Importantly, the tested extracts demonstrated no toxic effects on normal human liver (HepG2), thyroid (Nthy-ori 3-1), or breast (MCF10A) cells, indicating a favorable safety profile. Full article

Osteoporosis is characterized by an imbalance between bone formation and resorption, leading to decreased bone mass and an increased fracture risk, mainly associated with aging. Current treatments include anti-resorptive and anabolic drugs. However, these often have side effects, leading many patients to seek natural biological alternatives. We have demonstrated previously that hops extract, rich in compounds with estrogenic activity classified as phytoestrogens, exerts osteogenic effects by promoting the osteoblastic differentiation of bone marrow stem cells (BMSCs) while inhibiting osteoclast activity in vitro. In our study, young male Sprague Dawley rats were randomized into two groups: one received hops extract (LPL, 1% w/v in drinking water) for two months, and the other drank water alone (C). The rats were euthanized, and their femurs were dissected and processed for static histomorphometry and bone biomechanics. Additionally, BMSCs were isolated from the humeri to evaluate their osteogenic potential. Our result demonstrated that LPL treatment enhanced the osteogenic potential of humeral BMSCs in ex vivo assays, upregulating osteogenic genes and downregulating pro-resorptive markers. These findings correlated with improved femoral bone microarchitecture and biomechanical parameters. In conclusion, a two-month treatment with LPL enhanced the osteogenic capacity of BMSCs, improving bone microarchitecture and biomechanical properties. These results suggest its potential as a natural alternative for promoting bone health. Full article

This study investigates the therapeutic potential of sophoricoside and its aglycone metabolite, genistein, derived from Styphnolobium japonicum L. fruit, as natural alternatives to hormone replacement therapy for postmenopausal symptom management. Using Lactobacillus plantarum to model intestinal biotransformation, we compared glycoside-rich (Rex) and aglycone-rich (Rex-AG) extracts in ovariectomized rats. Both treatments significantly reduced weight gain and alleviated vaginal dryness, with Rex demonstrating superior thermoregulatory stabilization. Histological and molecular analyses revealed preserved trabecular bone integrity through the downregulation of RANKL and upregulation of TGF-β. Both extracts exhibited potent anti-inflammatory effects in adipose tissue, suppressing IL-6 and TNF-α, while regulating adipogenesis markers (FABP4, KLF, leptin, PPARγ) more effectively than 17β-estradiol. Serum genistein concentrations confirmed its efficient biotransformation and systemic bioavailability. Importantly, the treatments showed favorable safety profiles with no adverse effects on organ weight. These findings establish S. japonicum L. fruit-derived phytoestrogens as promising candidates for the comprehensive management of postmenopausal symptoms, offering an efficacious and safer alternative to conventional hormone therapy. Full article

Background: Premenstrual syndrome is characterized by emotional changes, including anxiety and depression symptoms, which may be treated with anxiolytic and antidepressant drugs, as well as estrogen therapy. However, steroidal estrogen therapy is contraindicated for patients with a potential risk of developing estrogen-dependent cancers through interactions with estrogen receptor α (ERα). Alternatively, genistein produces estrogenic effects in animals and humans at dietary dosages that act on the nuclear and membrane ERα, estrogen receptor β (ERβ), and the G-protein-coupled estrogen receptor (GPER). These receptors are likely involved in the anxiety symptoms observed in premenstrual disorders. The objective of this study was to evaluate the effects of genistein and 17β-estradiol on anxiety-like behavior and the plasma concentrations of estradiol and progesterone throughout the ovarian cycle of Wistar rats. Methods: The effect of the administration of 0.09 mg/kg of genistein or 17β-estradiol was evaluated using the elevated plus maze (EPM) test, locomotor activity test (LAT), and light/dark box (LDB) test, as well as by assessing the plasma concentrations of estradiol and progesterone, while considering the ovarian cycle phases. Results: Higher levels of anxiety-like behavior were detected in the metestrus–diestrus phase compared to the proestrus–estrus phase, which was associated with low concentrations of estradiol. Genistein, similarly to 17β-estradiol, significantly reduced anxiety-like behaviors in the EPM and LDB; however, 17β-estradiol, but not genistein, significantly increased the plasma estradiol concentration. No significant changes were found in locomotor activity or the plasma progesterone concentrations due to the treatments. Conclusions: These findings suggest that genistein may be useful in the development of alternative therapies to reduce the anxiety associated with low steroid hormone concentrations, which occur in premenstrual syndrome. Genistein could be an alternative to steroidal estrogen therapy to avoid potential side effects due to estradiol or antidepressant treatments, although it still requires medical care. Full article

Among the distressing side effects of cancer treatments, hair loss is one of the most disturbing for the quality of life and adherence to therapy in breast cancer patients. Many patients take nutritional supplements to prevent hair loss or enhance regrowth. Based on their mechanism and timing of use, nutritional supplements could be divided into safe, cautious, debated, and contraindicated categories. Non-contraindicated supplements generally include safe supplements like vitamin D, which is not known to interfere with cancer treatments. Those that are contraindicated include phytoestrogens and compounds affecting estrogen pathways because of the risk of stimulating tumor growth in cancers sensitive to estrogen. Antioxidants like tocotrienols and resveratrol are given judiciously because of potential interference with cancer therapies dependent on reactive oxygen species. Supplements debated, including nicotinamide, folate, and iron, pose a risk by promoting cellular proliferation or altering the tumor microenvironment. Biotin is nontoxic but interferes with blood test results and is thus difficult in cancer monitoring. Evidence regarding nutritional supplements’ safety and efficacy in this context is conflicting. Management by an oncologist is required along with more studies to clearly establish the safety parameters and efficacy guidelines. Full article

Labisia pumila var. alata (LP) is an herbaceous shrub commonly used by women to promote health and vitality, alleviate postmenopausal symptoms, and enhance libido. Research indicates that LP possesses significant oestrogenic and antiproliferative properties towards breast cancer; however, the specific mechanisms involved remain unclear. We investigate the oestrogenic effects of LP in inducing apoptosis in human breast adenocarcinoma (MCF-7) cells and the mechanisms underlying this process. Docking analysis reveals that the phytoestrogens in LP can bind to oestrogen receptors (ER), specifically ERα and ERβ. MTT assays demonstrate that LP has a dose- and time-dependent antiproliferative effect on MCF-7 cells. Furthermore, the antiproliferative activity of LP on MCF-7 cells is inhibited by Fulvestrant, indicating that its effects are mediated through oestrogen receptors. Flow cytometry analysis shows that the antiproliferative effect of LP results from the induction of apoptosis in MCF-7 cells. The activation of caspase 3, along with caspase 8 and caspase 9, suggests that LP triggers apoptosis through both intrinsic and extrinsic pathways. The findings regarding the aqueous extract of LP and its impact on the proliferative activity of MCF-7 cells may have significant therapeutic and preventive implications for future drug development, particularly in the context of breast cancer. Full article

Objectives: Ischemic stroke is a severe neurological disorder with high morbidity, mortality, and disability rates, posing a substantial burden on patients, families, and healthcare systems. Soy isoflavone (SI), a naturally occurring phytoestrogen, has demonstrated promising neuroprotective effects. This study aimed to evaluate the anti-stroke efficacy of SI and elucidate its underlying mechanisms through integrated phytochemical profiling, network pharmacology, and both in vitro and in vivo experimental validation. Methods: Active constituents of SI were extracted via reflux and identified using liquid chromatography–mass spectrometry (LC-MS). Network pharmacology was employed to predict therapeutic targets and signaling pathways. The neuroprotective effects of SI were first assessed in PC12 cells subjected to oxygen–glucose deprivation/reoxygenation (OGD/R) injury in vitro. For in vivo evaluation, transient cerebral ischemia–reperfusion injury was induced using the bilateral common carotid artery occlusion (BCCAO) model in adult male ICR rats (27.3 ± 1.8 g; 6–8 weeks old), obtained from the Shanghai Experimental Animal Center, Chinese Academy of Sciences. Forty-eight rats were randomly assigned into four groups (n = 12): sham, model (BCCAO), SI-treated (100 mg/kg, oral gavage for 5 days), and edaravone (EDA)-treated (10 mg/kg, i.p., positive control). All procedures were approved by the Institutional Animal Care and Use Committee of Changchun Normal University (Approval No. 2024003, 13 March 2024) and conducted in accordance with the NIH guidelines and ARRIVE 2.0 reporting standards. Results: In vitro, SI significantly enhanced PC12 cell viability from 57.23 ± 2.88% to 80.76 ± 4.43% following OGD/R. It also reduced intracellular Ca²⁺ by 58.42%, lactate dehydrogenase (LDH) release by 37.67%, caspase-3 activity by 55.05%, and reactive oxygen species (ROS) levels by 74.13% (p < 0.05). A flow cytometry analysis revealed that OGD/R increased the apoptosis rate from 5.34% (control) to 30.85% (model group), which was significantly attenuated by SI treatment, especially in the 560 µg/mL group (20.00%), followed by the 140 and 280 µg/mL groups. In vivo, SI improved neurological scores from 8.3 ± 1.09 to 6.8 ± 1.68, reduced cerebral infarction volume by 18.49%, and alleviated brain edema by 10.42% (p < 0.05). SI also decreased malondialdehyde (MDA) and LDH levels by 31.15% and 39.46%, respectively, while increasing the activity of antioxidant enzymes: superoxide dismutase (SOD) by 11.70%, catalase (CAT) by 26.09%, and glutathione peroxidase (GSH-px) by 27.55% (p < 0.01). Scratch assay results showed that SI restored the impaired migratory ability of the OGD/R-treated PC12 cells, further supporting its role in cellular repair. A Western blot analysis demonstrated the upregulation of nuclear factor erythroid 2–related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase 1 (NQO1) and the downregulation of Kelch-like, ECH-associated protein 1 (Keap1) in the cerebral ischemia–reperfusion model. Conclusions: These findings indicate that soy isoflavone confers significant neuroprotective effects against cerebral ischemia–reperfusion injury by enhancing endogenous antioxidant defense mechanisms, reducing oxidative stress, inhibiting apoptosis, and promoting cell migration. The protective effects are likely mediated through the activation of the Nrf2/Keap1 signaling pathway, supporting the therapeutic potential of SI in ischemic stroke treatment. Full article

(1) Background: Diet plays a crucial role in the intake of phytoestrogens, which are closely related to the pathogenesis of some pregnancy complications. However, no studies have explored the potential association between soy isoflavones, a type of phytoestrogen, and the risk of hyperemesis gravidarum (HG). This study aims to investigate the correlation between dietary intake of soy isoflavones and the risk of HG. (2) Methods: As part of the China Birth Cohort Study (CBCS), 2418 pregnant Chinese women (mean age: 31.2 ± 3.4 years) were enrolled between April 2021 and September 2022. Dietary intake was evaluated using a validated 108-item semi-quantitative food frequency questionnaire, with soy isoflavones intake estimated based on five food groups. HG was defined as a condition characterized by a pregnancy-specific vomiting score (PUQE) ≥ 13, weight loss of ≥5% due to severe nausea and vomiting before 16 weeks of gestation, inability to eat or drink normally, significant limitations in daily activities due to severe nausea or vomiting, or the need for hospitalization caused by the condition. The association between soy isoflavones intake and HG was analyzed using binary logistic regression and restricted cubic spline regression. (3) Results: Among all participants, 212 women (8.8%) were diagnosed with HG. The dietary intake of soy isoflavones was 14.56 (IQR: 9.89, 25.36) mg/d. After full adjustment for confounding factors, the results indicated that individuals with the highest dietary intake of soy isoflavones had a lower risk of developing HG (OR: 0.56, 95% CI: 0.36, 0.88. P_trend = 0.012). (4) Conclusions: Higher dietary intake of soy isoflavones is associated with a reduced risk of HG. We advocate for a dietary approach to the management of HG that prioritizes the intake of legume-rich foods, particularly those abundant in soy isoflavones. Full article

Serotonin (5-HT), dopamine (DA), and norepinephrine (NE) are key monoamine neurotransmitters regulating behaviors, mood, and cognition. 5-HT affects early brain development, and its dysfunction induces brain vulnerability to stress, raising the risk of depression, anxiety, and autism in adulthood. These neurotransmitters are synthesized from tryptophan and tyrosine via hydroxylation and decarboxylation, and are metabolized by monoamine oxidase (MAO). This review aims to summarize the current findings on the role of dietary phytochemicals in modulating monoamine neurotransmitter biosynthesis, metabolism, and function, with an emphasis on their potential therapeutic applications in neuropsychiatric disorders. Phytochemicals exert antioxidant, neurotrophic, and neurohormonal activities, regulate gene expression, and induce epigenetic modifications. Phytoestrogens activate the estrogen receptors or estrogen-responsive elements of the promoter of target genes, enhance transcription of tryptophan hydroxylase and tyrosine hydroxylase, while inhibiting that of MAO. These compounds also influence the interaction between genetic and environmental factors, potentially reversing dysregulated neurotransmission and the brain architecture associated with neuropsychiatric conditions. Despite promising preclinical findings, clinical applications of phytochemicals remain challenging. Advances in nanotechnology and targeted delivery systems offer potential solutions to enhance clinical efficacy. This review discusses mechanisms, challenges, and strategies, underscoring the need for further research to advance phytochemical-based interventions for neuropsychiatric diseases. Full article

Background/Objectives: Flavonoids are common ubiquitous components of plants and are consumed by humans and livestock in their diets. Many different activities have been proposed for a variety of flavonoids that play a role in the benefits of a plant-rich diet. On the downside, excessive exposure to some flavonoids comes with a risk of endocrine disruption. Our objective was to define the structural elements of flavones and selected other flavonoids required for endocrine-disrupting activities on each of four steroid receptors, estrogen, androgen, progesterone, and glucocorticoid receptors. Methods: This work presents a systematic screen for the hormone agonist or antagonist activity of a selected panel of flavonoids on estrogen, androgen, progesterone, and glucocorticoid receptors. The screen is focused on the positional requirements of hydroxyl substituents on the flavone backbone. Results: Each receptor exhibited a distinct pattern for structural requirements of the flavones to impact receptor signaling. The most active flavones exhibited antagonist activity on androgen and progesterone receptors with an IC₅₀ of 0.5 and 2 µM, respectively. Flavones only exhibited weak antagonism on glucocorticoid receptors. When active, flavones acted as estrogen receptor agonists. The findings were utilized to design and synthesize a novel flavone, 3-fluoro, 6,4′-dihydroxyflavone 14, that displays increased potency as an estrogen agonist (EC₅₀~30 nM). Modeling of the binding of this novel flavone predicts increased preference for ERα versus ERβ relative to the estrogenic phytoestrogen, genistein. Conclusions: The structural requirements for flavones to act as estrogen agonists and antagonists of other steroid receptors are defined. The synthesis of a novel flavone offers potential for topical applications where systemic estrogen activity is undesired. However, the results highlight the potential for endocrine disruption when certain flavones are consumed in quantity as supplements. Full article