Search Results (390)

Menopause represents a key transitional phase in women’s health, characterized by declining estrogen levels and increased risk for cardiometabolic, musculoskeletal, and urogenital disorders. Beyond its endocrine roots, emerging evidence highlights the gut microbiome as a critical modulator of systemic hormonal balance. This review synthesizes current understanding of the bidirectional relationship between estrogen and the gut microbiome and its implications for women’s health during menopause. Evidence from current studies reveals distinct findings across populations, reflecting the complexity of estrogen regulation in part by the gut microbiome (i.e., estrobolome). While no ideal gut microbial composition has been identified for women across stages of perimenopause, likely due to geographically unique gut microbiome profiles among healthy women, greater microbial diversity has been positively associated with improved estrogen regulation. Conversely, reduced diversity and altered Firmicutes/Bacteroidetes ratios have been linked to biomarkers of inflammation during perimenopause, which is a key driver across many perimenopausal symptoms. Although hormone replacement therapy remains the primary clinical intervention during perimenopause, we highlight emerging evidence on the adjuvant potential of diet, synbiotics, phytoestrogens, and strain-specific probiotics in modulating the estrogen–gut microbiome axis for improved health span trajectories and better symptom management. Future longitudinal studies integrating diet, gut microbiome profiles and symptom trajectories are essential to clarify these mechanisms across ethnicity and geography. Ultimately, understanding localized diet–microbiome interactions will enable the development of accessible, personalized, and non-hormonal strategies to complement and increase agency in proactive management during the perimenopausal transition. Full article

The gonadal development of Japanese eels (Anguilla japonica) plays a crucial role in the success of artificial breeding. Soy isoflavones, a class of phytoestrogens commonly found in aquafeeds, have shown potential in enhancing gonad development in fish. The present study evaluated the effects of dietary soy isoflavones on gonadal development, growth performance, histology, sex hormone levels, vitellogenin content, and expression of related genes in female Japanese eel broodstock. A 4-week feeding trial was conducted with 120 two-year-old female eels randomly assigned to four groups and fed diets containing 0 (C), 0.1 (L), 0.5 (M), and 0.9 (H) mg/g of soy isoflavones. The results indicated that gonadal development was enhanced in the M and H groups, as evidenced by a significantly higher gonadosomatic index (GSI) and increased oocyte cross-sectional area (CSA) in M group, and greater nutrient accumulation in both the M and H groups. The expression of er and cyp19a genes in the ovary was downregulated in the treatment groups, leading to decreased serum estradiol (E2) and increased testosterone levels. Furthermore, hepatic vtg gene expression was upregulated in the M and H groups, though VTG protein content remained unchanged, suggesting an initiation of vitellogenesis at the transcriptional level. In conclusion, dietary soy isoflavones at 0.5–0.9 mg/g provide an effective pretreatment strategy to enhance early ovarian development in Japanese eel broodstock, potentially improving their responsiveness to subsequent hormonal induction in artificial breeding programs. Full article

Reproductive management in goats remains challenging due to seasonal breeding and the use of hormones that raise concerns about immunogenicity, cost, sustainability, and animal welfare. In this study, we evaluated date palm pollen (Phoenix dactylifera L.) (DPP) as a natural source of estrogenic compounds capable of modulating reproductive function. DPP was extracted using methanol, ethanol, acetone, and hexane, and the extracts were analyzed by ultra-performance liquid chromatography. Quercetin and coumestrol were detected in the methanolic and ethanolic extracts at comparable levels (quercetin 0.043–0.044 mg/g; coumestrol 0.987–1.015 mg/g of extract) (p > 0.05). The acetone extract contained significantly lower concentrations (quercetin 0.017 mg/g; coumestrol 0.033 mg/g of extract), while the hexane extract showed no detectable amounts. Molecular docking using the crystallographic structure of estrogen receptor alpha (PDB:6PIT) showed that both compounds interact with key residues of the receptor’s ligand-binding domain. Coumestrol exhibited the highest affinity (−9.3 kcal/mol), surpassing 17-β estradiol (−8.9 kcal/mol), forming several hydrogen bonds and hydrophobic contacts. Quercetin showed a lower affinity (−7.2 kcal/mol) but maintained stabilizing interactions compatible with partial agonist activity. Overall, methanol and ethanol were the most effective solvents for extracting phytoestrogens from DPP, and the findings support their potential as natural alternatives to hormones for estrus induction in goats. Full article

Background/Objectives: The menopausal decline in estrogen levels accelerates age-related changes, including visceral adiposity, insulin resistance, sarcopenia, osteoporosis, and endothelial dysfunction. While nutrition independently influences these outcomes, the interactive role of estrogen signaling and nutrient metabolism in healthy aging remains underexplored. This article evaluates these interactions. Methods: We conducted a narrative synthesis of studies examining estrogen’s effects on energy balance, adipose regulation, muscle, bone, and cardiovascular health, with an emphasis on estrogen-like nutritional modulators and phytoestrogens. In addition, we present original experimental data from our laboratory investigating sex-specific vascular responses to G protein-coupled estrogen receptor (GPER) activation using functional myography in isolated rat aortic rings from young adult and middle-aged rats (n = 6–8 per group) to assess responses to the GPER agonist G-1 (1.0 μM). Results: Literature evidence demonstrates that estrogen supports macronutrient utilization, suppresses adipose inflammation, preserves bone density, and promotes endothelial function. Phytoestrogens may engage estrogen-responsive pathways to mitigate age-related physiological decline. Our original findings show that GPER agonism enhances both contractile and vasodilatory responses in female (p < 0.05) but not male rat aortas, providing mechanistic evidence of sex-specific vascular estrogen signaling. These results suggest that dietary phytoestrogens and nutrient-rich dietary patterns may, in part, activate GPER-dependent pathways to support cardiovascular resilience in aging women. Conclusions: Estrogen–nutrition interactions are central to metabolic adaptation and healthy aging. Our findings highlight GPER as a functionally resilient pathway in aging vasculature, offering a putative mechanistic link for nutritional modulation. However, direct translation of these findings to human clinical outcomes remains to be established. Precision nutrition strategies targeting GPER represent a promising framework for healthy aging, though large-scale human trials are necessary to confirm these receptor-specific effects. Full article

Background: Tendinopathy remains a prevalent musculoskeletal disorder with limited disease-modifying pharmacotherapy. This study aimed to identify a reparative agent from the traditional medicinal herb Eucommiae Cortex and elucidate its mechanism of action. Methods: A bioactive fraction was first identified through a bioactivity-guided strategy using tenocyte cytoprotection and migration assays, then characterized by UHPLC-HRMS/MS. Its major constituent, aucubin (AU), which mirrors the fraction’s key pharmacological activities, was evaluated both in vitro and in vivo. In H₂O₂-injured tenocytes, AU’s effects on viability, apoptosis, oxidative stress (ROS, MDA, SOD) and inflammation (IL-1β, TNF-α) were assessed, with specific focus on estrogen receptor (ER) pathway involvement using pharmacological tools (17β-estradiol and (R, R)-THC). In a collagenase-induced Achilles tendinopathy model using male SD rats, AU’s therapeutic efficacy was evaluated via multimodal assessment: ultrasonography, histopathology (H&E, Masson’s trichrome, Sirius red), TEM, immunohistochemistry, and biochemical analysis of tissue markers. Results: AU effectively attenuated H₂O₂-induced tenocyte injury by enhancing viability, reducing apoptosis, and mitigating oxidative/inflammatory stress. These effects were mimicked by 17β-estradiol and reversed by the selective ERβ antagonist (R, R)-THC, indicating ERβ dependence. In vivo, AU treatment promoted structural and functional recovery, improved collagen maturity (increased Col I/Col III ratio and fibril diameter), suppressed matrix degradation (MMP-3, MMP-13) and apoptosis, and reduced oxidative stress and inflammation in tendon tissue. Conclusions: This study identifies aucubin as a novel phytoestrogenic compound from Eucommiae Cortex that promotes tendon repair through an ERβ-mediated mechanism. These findings position ERβ activation as a promising therapeutic strategy for tendinopathy and highlight AU as a promising lead compound for further development. Full article

African American (AA) women often experience earlier onset and more severe menopause symptoms, especially vasomotor symptoms (VMSs) like hot flashes, compared to other groups. However, limited research has examined the effectiveness and acceptability of menopause treatments in this population. This scoping review synthesized evidence on pharmacological (e.g., hormone replacement therapy [HRT], SSRIs, venlafaxine, nitroglycerin) and holistic (e.g., dietary changes, physical activity [PA], supplementation) approaches for managing menopause symptoms in AA women. Using Joanna Briggs Institute and PRISMA-ScR guidelines, a scoping review was conducted, guided by the PCC framework. Four databases (CINAHL, PsycInfo, PubMed, Scopus) were searched for English-language studies (2010–2025) involving AA women aged 40–65. Eligible studies included RCTs and observational designs with ≥10% AA participants. Data were charted and synthesized descriptively. Fourteen U.S.-based studies (11–53% AA representation) were included. Pharmacological treatments—especially HRT and SSRIs—were effective for VMSs and mood symptoms. Holistic approaches showed mixed outcomes; PA and magnesium offered modest benefit, while phytoestrogens sometimes worsened memory. Race-specific results were rarely reported. Effective pharmacological options exist, but evidence tailored to AA women is lacking. Future research must ensure greater AA representation and culturally responsive approaches to menopause care. Full article

Bakuchiol (BAK), a natural meroterpenoid with antioxidant, anti-inflammatory and anticancer properties, has recently gained attention as a potential adjunct in breast cancer therapy. This review contextualizes breast cancer as a major global health challenge and highlights BAK as a bioactive compound capable of modulating pathways relevant to tumor development and progression. A structured literature search identified studies examining its molecular activity, pharmacological profile, and effects on breast cancer cells and stem cells. Results show that BAK influences oxidative stress regulation, mitochondrial function, apoptosis and estrogen receptor signaling while also affecting PI3K/AKT, MAPK, NF-κB, and EMT-related pathways. In breast cancer models, BAK acts as a selective phytoestrogen, induces S-phase arrest, activates the ATM/ATR–Chk1/Chk2 axis, and triggers mitochondrial apoptosis, particularly in ERα-positive cells. It also suppresses breast cancer stem-cell renewal, promotes BNIP3- and DAPK2-mediated apoptosis, reduces metabolic and transcriptional drivers of metastasis, and shows enhanced anticancer activity in derivative forms. These findings suggest that BAK may provide therapeutic benefit across several mechanisms central to breast cancer biology. In this review, the inclusion criteria encompassed publications describing the action of bakuchiol, its chemical and pharmacological properties, as well as its role in the treatment of various conditions, including cancers. Exclusion criteria included works not related to BAK or its therapeutic use in breast cancer, as well as publications that did not meet basic scientific standards, such as lacking methodological rigor or presenting a low level of scientific evidence. However, current evidence is predominantly in vitro, and limitations such as poor bioavailability and lack of clinical validation underscore the need for further in vivo and translational studies before therapeutic application can be established. Full article

This study evaluated 65 commercially available pet feed samples, including 33 cat feeds and 32 dog feeds (dry and wet formulations), for the presence of organic contaminants. These included mycotoxins, pesticides, pharmaceutical residues/veterinary drugs, and plant-based bioactive compounds. A suspect screening strategy was employed using QuEChERS extraction followed by LC-LTQ/Orbitrap HRMS analysis. A total of 29 compounds were tentatively identified within 186 detections. In total, 76.9% of the samples were contaminated with mycotoxins. Aflatoxins (B1, B2, G1, and G2), T2 toxins, and HT2 toxins were dominant, with Aflatoxin B1 occurring in 33.8% of the samples and exhibiting a higher prevalence in dry feeds than in wet feeds. Pesticides were present in 72.0% of the dry formulations, including aclonifen and pirimiphos-methyl, but were present in only 11% of the wet formulations. Plant-based bioactive compounds, including phytoestrogens, were identified in 51% of the samples, highlighting toxicologically relevant candidates that merit prioritization for targeted confirmation, particularly in cat feeds. Pharmaceuticals were found in 23.8% of dry feeds (sparfloxacin and fumagillin). Overall, the HRMS-based, standard-free suspect screening workflow provides an early-warning overview of multi-class co-occurrence patterns in complex pet feed matrices and supports the prioritization of candidates for subsequent confirmatory analysis. Full article

The mycotoxin zearalenone (ZEN), commonly found in contaminated food and feed, poses a significant threat to human and animal health, particularly to reproductive function. Mitigating its toxicity represents a critical research priority in food safety. Apigenin (AP) is a naturally occurring dietary flavonoid with phytoestrogenic properties and exhibits diverse pharmacological activities. In this study, we investigated the protective effects of AP against ZEN-induced apoptosis and oxidative stress in Swine Testis (ST) cells and elucidated its underlying mechanisms. The identity of ST cells was verified via RT-PCR and agarose gel electrophoresis. ST cells were treated with 40 μM ZEN and 1 μM and 0.1 μM AP for 24 h. Cell viability was detected via CCK8 and EdU assays, cytotoxicity was evaluated via LDH assay, cell cycle and apoptosis levels were analyzed via flow cytometry, and the mechanism by which AP alleviated the damage caused by ZEN to ST cells was preliminarily revealed using RNA-Seq technology. Further, the expression levels of related genes and proteins were detected by qRT-PCR and Western blot. Our results show that 1 μM or 0.1 μM AP effectively attenuated the cytotoxicity induced by 40 μM ZEN in ST cells, as evidenced by restored cell viability, reduced the LDH level, normalized cell cycle progression, reduced apoptotic rates, and enhanced antioxidant capacity. RNA-Seq analysis was coupled with molecular validation and used to elucidate the mechanisms underlying AP-mediated protection against ZEN-induced cellular injury. It is shown that ZEN suppressed the expression of LRP5, a pivotal gene in the Wnt signaling pathway, along with its downstream effector c-Myc. Conversely, treatment with 1 μM or 0.1 μM AP upregulated the expression of LRP5, iASPP, and TRAF2 at both transcriptional and translational levels. Importantly, the protective effects of AP were abrogated with IWR-1-endo, a specific Wnt pathway inhibitor, confirming pathway dependency. Collectively, our findings show that AP alleviates ZEN-induced oxidative stress and apoptosis in ST cells through the upregulation of LRP5 and subsequent activation of the Wnt signaling pathway. This study provides molecular evidence supporting the potential clinical application of AP as a preventive agent against ZEN-induced reproductive toxicity. Full article

Background/Objectives: Osteoporosis is highly prevalent and contributes substantially to morbidity and mortality, yet long-term concerns about pharmacologic therapies leave a major treatment gap. Soy isoflavones have been investigated as safer alternatives, but results across trials are inconsistent. A key unresolved issue is the equol-producer phenotype, the gut microbial ability to convert daidzein to S-equol, the most bioactive isoflavone metabolite, which may explain much of this variability. This narrative review synthesizes mechanistic, translational, and clinical evidence to clarify the potential skeletal relevance of S-equol. Methods: Literature was identified through PubMed and Scopus searches (January 2000–October 2025) for experimental, mechanistic, and clinical studies examining S-equol, estrogen receptor β (ERβ), and bone metabolism, with emphasis on equol-producing status, bone strength and bone microarchitecture. Results: S-equol acts as a high-affinity ERβ agonist with antioxidant and anti-inflammatory properties but lacks the carcinogenic or thrombotic risks linked to ERα activation. In estrogen-deficient rodent models, S-equol improves trabecular bone volume by 10–20%, increases trabecular number, and enhances biomechanical strength. These findings align with preclinical evidence demonstrating that S-equol preserves trabecular microarchitecture, enhances bone strength, and reduces bone turnover. A limited number of human trials show reductions in bone resorption by 20% at a daily dose of 10 mg S-equol. In contrast, trials of soy isoflavones in humans have produced inconsistent findings, partly because of substantial variability in equol-producer phenotype among participants and the reliance on dual-energy X-ray absorptiometry, which cannot distinguish trabecular from cortical compartments. Advanced bone imaging and microbiome-informed approaches enable the precise evaluation of S-equol’s skeletal effects on trabecular bone and cortical bone, separately. Conclusions: S-equol represents a promising model for “precision nutrition,” where microbiome, hormonal, and host factors converge with potential to prevent age-related bone fragility. Rigorous trials that integrate microbiome phenotyping and advanced imaging are needed to validate this approach, translate mechanistic promise into clinical benefit, and better define safety. Full article

Isoflavones are natural compounds abundantly found in soybeans, recognized for their anticancer potential, primarily through their activity as phytoestrogens, which inhibit estrogen receptors. Because cancer remains one of the leading causes of mortality worldwide, identifying compounds that may complement chemotherapy is of great interest. In this review, we summarize advances reported over the past decade regarding the antitumor properties of isoflavones, with emphasis on both in vitro and in vivo effects, as well as chemical, botanical, and pharmacological aspects. A literature search was conducted using the PubMed database covering studies published from January 2014 to April 2025 using the following keywords: ‘isoflavones’ and ‘anticancer’, ‘antitumoral’, and ‘antiproliferative’ and ‘cytotoxicity’. Genistein and daidzein emerge as the most extensively studied isoflavones, with well-documented anticancer activity. Reported anticancer effects include induction of apoptosis, ROS generation, cell cycle arrest, inhibition of cell migration and invasion, loss of mitochondrial membrane potential, modulation of estrogen-related pathways, and antiangiogenic activity. In addition to these mechanistic findings, several isoflavones demonstrated significant tumor growth inhibition in xenograft models, reinforcing their translational potential. Additionally, synergistic interactions with chemotherapeutic drugs and natural compounds and new drug delivery systems have been described. Breast and prostate cancer cell lines were the most investigated due to isoflavones’ estrogen-like effects. However, the cell death mechanisms of newly discovered compounds still require further investigation. Full article

6-Prenylnaringenin (6-PN) is a natural compound which occurs in some plants, but the primary dietary source for humans is beer. This compound exhibits broad and potent antimicrobial, anticancer, and neuroactive properties, and weak estrogenic effects. Currently, hop extracts standardized for 6-PN content (relative to other prenylflavonoids) are commercially available and utilized in the non-hormonal treatment of menopause. It is probable that in the future, 6-PN will be employed in the prevention or treatment of non-hormone-dependent cancers and infectious diseases, as well as a sedative, hypnotic, and analgesic agent. Further research is essential to precisely determine the exact mechanisms of action of 6-PN and, critically, to leverage its unique therapeutic profile. This review synthesizes current evidence, highlighting that 6-PN warrants priority investigation as a core scaffold for novel drug development, particularly as a GABA_A positive allosteric modulator and a synergistic antimicrobial agent, potentially offering a safer alternative to more potent phytoestrogens found in hops. Full article

Daidzein and genistein are abundant in soy-rich foods, whose supplementation has been proposed to have beneficial effects on several diseases, including diabetes mellitus and obesity. 17β-estradiol (E2) enhances the expression of the Slc2a4 gene and GLUT4 protein in adipose tissue, increasing glucose consumption and contributing to glycemic control. We investigated, in 3T3-L1 adipocytes, the effect of low and high doses of daidzein and genistein on Slc2a4/GLUT4 expression and the participation of estrogen receptors 1/2 (ESR1/ESR2) in the regulations observed. Differentiated adipocytes were cultivated, for 24 h, in the presence of 17β-estradiol (E2, 10 nM), daidzein (10 nM–150 μM) and genistein (10 nM–50 μM), with or without ESR1 or ESR2 antagonists. Daidzein/genistein at a low dose (10 nM) increased Slc2a4/GLUT4 expression (50%, p < 0.05), an effect abrogated by an ESR1 antagonist, mimicking the effect of E2. However, maximal doses of daidzein and genistein reduced, in a ESR1-mediated mechanism, the expression of mRNA (by 47% and 60%, p < 0.001) and the protein (by 29% and 36%, p < 0.01), respectively, for daidzein and genistein, as compared to E2. In conclusion, in adipocytes, daidzein and genistein have a biphasic ESR1-mediated effect: while low concentrations increase the expression of Slc2a4/GLUT4, high concentrations decrease it, the former predisposing to an adipogenic effect, the latter to a diabetogenic condition. Full article

This study examined the effects of Bacillus probiotic strains on red abalone Haliotis rufescens reproductive performance. We supplemented plant- and fish-based feeds and compared them to fresh giant kelp Macrocystis pyrifera as a control diet. Over 180 days, abalone fed the plant–probiotic diet reached higher female gonadal maturation, with 56% of females attaining the maximum Visual Gonad Index (VGI 3). Additionally, plant-based treatment showed a female-biased sex ratio (1.5:1 female-to-male ratio, F:M) compared with the kelp control treatment (0.8:1 F:M). These results suggest that probiotics can improve nutrient utilization from soybean meal and may enhance the bioavailability of phytoestrogens and other bioactive compounds, contributing to reproductive outcomes. Although the mechanisms remain to be confirmed, this approach provides a promising strategy to reduce reliance on fishmeal and wild macroalgae while supporting faster reproductive cycles in abalone aquaculture. Future research should focus on biochemical validation, molecular pathways, and multigenerational trials to ensure the long-term safety and sustainability of probiotic–plant-based feeds. Full article

Background: Hormonal fluctuations significantly influence skin physiology, affecting collagen production, sebum regulation, pigmentation, and tissue repair. Hormonal therapies are increasingly used in cosmetic dermatology to address age-related and hormone-dependent skin changes. Methods: This narrative review synthesizes the current literature on the mechanisms, clinical applications, and future directions of hormonal therapies in dermatologic aesthetics. Studies were selected through a comprehensive search on PubMed, Scopus, and Web of Science. Results: Estrogens, androgens, progesterone, and other hormones act on skin through specific receptors, modulating fibroblast, sebocyte, and melanocyte activity. Clinical applications include hormone-based strategies for anti-aging, acne, melasma, alopecia, and postmenopausal atrophy. Both systemic (e.g., HRT) and topical (e.g., clascoterone, phytoestrogens) approaches are discussed. Safety concerns, including systemic absorption and off-label use, require careful evaluation. Emerging technologies such as SERMs, nanocarriers, and regenerative combinations suggest promising future avenues. Conclusions: Hormonal therapies offer a biologically rational and increasingly evidence-based tool in cosmetic dermatology. Responsible integration into clinical practice depends on personalized approaches, ethical prescribing, and further research on long-term safety and efficacy. Full article