Search Results (396)

Background/Objectives: Phytoestrogens are secondary plant metabolites produced via the phenylpropanoid pathway. They include a broad spectrum of chemical compounds, such as phenolics, flavonoids, isoflavones, coumestans, lignans, and others. Their chemical structures resemble those of estradiol, and they exhibit biological effects similar to those of human estrogens, influencing many physiological processes throughout life in both men and women—including the timing and progression of puberty. Methods: The literature search included databases such as PubMed, Scopus, Web of Science, and Google Scholar with the use of specific keywords. Studies were considered eligible if they reported original findings from observational studies (cohort, case–control, and cross-sectional) or from experimental studies. Results: Phytoestrogens can modulate estrogenic activity and interact with a variety of biological pathways. These compounds may play a role in human development and pubertal processes, contribute to overall health, and potentially help alleviate menopausal symptoms and reduce the risk of certain cancers. Conclusions: Phytoestrogens have numerous positive effects on the human body across various stages of life. Their overall impact and potency, however, seem to be influenced by factors such as intake level, individual genetic variability, and the specific phytoestrogen class consumed. Full article

Background/Objectives: The climacteric transition is a critical stage in women’s health characterized by significant endocrine, metabolic, cardiovascular, and autonomic changes that increase cardiometabolic vulnerability during midlife. This narrative review aimed to synthesize current evidence on body composition, heart rate variability and autonomic function, phytoestrogens & estrobolome interactions, and exercise-based lifestyle approaches during the climacteric transition. Methods: A structured literature search was conducted across four domains (body composition, heart rate variability, phytoestrogens, and exercise) using PubMed/MEDLINE, Web of Science, Scopus, Google Scholar, and the Cochrane Library. Studies were selected based on relevance, study design, and methodological rigor, and synthesized using a narrative approach. Additional thematic components, including dietary patterns and gut microbiota estrobolome interactions, were incorporated through targeted searches. Results: The climacteric transition is associated with increased visceral adiposity, reduced lean mass, insulin resistance, dyslipidemia, and a higher prevalence of metabolic syndrome, while body mass index may underestimate metabolically relevant adiposity. Altered autonomic regulation, reflected by reduced heart rate variability and sympathetic predominance, is linked to increased cardiovascular risk, although its independent contribution is influenced by aging and comorbidities. Mediterranean and plant-based dietary patterns may improve metabolic and inflammatory profiles and modulate estrogen metabolism through gut microbiota mechanisms. Phytoestrogens show potential benefits for vasomotor symptoms and selected metabolic markers, although evidence remains heterogeneous. Exercise interventions consistently improve body composition, cardiometabolic parameters, and autonomic function. Conclusions: A multidimensional lifestyle-based approach integrating exercise, dietary strategies, and modulation of estrogen-related pathways may help mitigate cardiometabolic risk and support healthier aging during the climacteric transition. Full article

Craft breweries generate a complex set of byproducts that exceed 2 million tons annually. Their disposal possesses material handling, financial, and environmental challenges. A mixture of these, namely trub, hops, and yeast, designated THYM^®, was evaluated biochemically and in a feeding trial to enhance its valuation. THYM contained approximately 3% α plus β hop acids, 0.2% xanthohumol (XN), and 35% crude protein. It exhibited antimicrobial activity, with a minimum inhibitory concentration of 137 ± 39 μg/mL for B. subtilis, and antioxidant activity, with 90 ± 13 μmol/g of Trolox equivalents. THYM presented positive results in bovine rumen microbial in vitro fermentations, decreasing methane production and the acetate:propionate ratio at 3 mg/mL. These results led to a nine-week feedlot trial with 45 Black Angus weanling steers on either a corn silage-based diet (CON), CON with monensin (MON) at 200 mg/animal, or CON with 1% THYM (THYM). Data were analyzed by SAS 9.4 with two orthogonal contrasts of CON vs. MON and THYM and MON vs. THYM. While average daily gain (ADG) and dry matter intake (DMI) did not differ among treatments, a tendency was observed for the THYM and MON groups to have a greater gain to feed ratio (ADG:DMI) when compared to CON (p = 0.07). The XN metabolite 8-prenylnarigenin, a potent phytoestrogen, was present in the serum of the THYM group at 4.0 ± 0.9 nM by mass spectrometry. These brewing byproducts, which can be drum-dried, were well tolerated and show potential value as a cattle growth promoter. Full article

Phytoestrogens are plant-derived phenolic compounds that structurally resemble endogenous estrogens and can exert both estrogenic and anti-estrogenic effects in animals. In ruminant nutrition, the main classes of phytoestrogens (isoflavones, lignans, stilbenes, coumestans and selected flavonoids) are supplied predominantly by legume forages and soybean-based feeds, in which concentrations can reach several mg/g of dry matter. After ingestion, these compounds are extensively metabolized by the rumen microbiota to derivatives with altered biological potency, such as equol and p-ethyl-phenol, which influence endocrine, immune and metabolic pathways. Experimental and field studies in cattle, sheep and goats indicate that dietary phytoestrogens may improve nitrogen utilization, immune competence, growth performance, antioxidant status and milk yield. However, they can also impair fertility, modify hormone profiles and compromise embryo survival in a compound-, dose-, and species-dependent manner. In this review, we summarize current knowledge on the botanical and nutritional sources, ruminal metabolism and transfer of phytoestrogens in ruminants, and critically examine their effects on blood metabolites, immune responses, growth and carcass traits and lactational performance and reproductive function. A structured literature search based on PRISMA principles was used to identify and appraise experimental and observational studies in both grazing and intensive production systems up to 2025. Remaining knowledge gaps and practical implications for the safe use of phytoestrogen-rich feeds in livestock production are highlighted. Full article

Physiological and metabolic adaptations during pregnancy may increase susceptibility to harmful environmental chemicals. High maternal BMI that perturbs the metabolic, inflammatory, and hormonal milieus could modulate toxicant effects on pregnancy outcomes. First-trimester targeted urinary exposomes of 119 women (BMI ≥ 25 = 55; BMI < 25 = 64) from the Michigan Mother–Infant Pair cohort were profiled to assess how BMI influences urinary exposomes and related biological responses. A validated approach measured 96 chemicals and biomarkers of oxidative stress and glucocorticoids. Women in both groups reported similar lifestyles and consumer product use. Women with high BMI had lower urinary concentrations of several chemicals than women with low BMI. Phytoestrogens, polycyclic aromatic hydrocarbons, and insect repellants showed a higher magnitude of positive associations with other markers of exposure, oxidative and glucocorticoid stress in the high-BMI group, while UV filters, flame retardants, and phthalates showed a higher magnitude of positive associations with oxidative stress markers in the low-BMI group. The patterns of associations of exposure markers with stress markers and pregnancy outcomes (gestational age and birthweight) differed by maternal BMI. This highlights the importance of incorporating maternal BMI into the evaluation of exposure burden and its effects, as a factor that may actively shape biological responses. Full article

Isoxanthohumol (IX) is a prenylated flavonoid derived from hop cones (Humulus lupulus) that is gaining increasing recognition for its potential biological effects. Despite numerous studies on its precursor, xanthohumol, studies on IX remain limited. Of particular interest is its metabolism, particularly its biotransformation by gut microbiota to 8-prenylnaringenin (8-PN), a potent phytoestrogen, which indicates the complex nature of its biological activity and potential health implications. This review summarizes the current state of knowledge on IX and its derivatives, covering their microbial metabolism, their impact on the gut microbiome, and the metabolic consequences of this conversion. Furthermore, it examines the relationship between the molecular structure of IX and its derivatives and their biological activity, highlighting existing research gaps and the need for further research on the safety and therapeutic potential of these compounds Full article

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