Search Results (268)

Metabolic dysfunction-associated steatotic liver disease (MASLD) develops when hepatic lipid acquisition and synthesis exceed the capacity for oxidation and very-low-density lipoprotein export. Flavonoids act on several components of this network, yet their therapeutic development is constrained by poor aqueous solubility, extensive intestinal and first-pass metabolism, variable activity of circulating metabolites, and limited information on hepatic exposure. Experimental studies link representative flavonoids to AMPK–SREBP-1c and PPARα signaling, mitochondrial quality control, Nrf2-dependent redox defense, inflammatory pathways, and the gut–liver axis. By contrast, the available randomized trials of quercetin, hesperidin, anthocyanins, green-tea catechins, EGCG, and soy isoflavones show at most modest changes in liver fat or biochemical markers and do not demonstrate metabolic dysfunction-associated steatohepatitis (MASH) resolution or fibrosis regression. Liposomal, lipid-based, polymeric, and nanocrystal formulations have improved dissolution, systemic exposure, or liver distribution in preclinical models, but comparative pharmacokinetics, chronic safety, manufacturability, and clinical efficacy remain poorly defined. The evidence therefore supports viewing flavonoids as formulation-dependent investigational candidates rather than established MASLD therapies. Progress will depend on chemically standardized products, exposure–response studies, clinically relevant models, and adequately powered trials using validated imaging or histological endpoints. Full article

Objective: This study assessed dietary soy isoflavone (SIF) intake among Chinese women ≥14 years, identified determinants, and evaluated adequacy against the Specific Proposed Level (SPL) in Chinese Dietary Reference Intakes, to inform targeted guidance. Methods: Intake was estimated using a distribution model combining 2017–2020 China National Food Consumption Survey data with SIF concentrations from food composition tables. Demographic differences and adequacy versus age-specific SPL were examined; supplemental doses were calculated for individuals below SPL. Results: Mean SIF intake was 14.77 mg/standard person-day, generally low. Significant differences (p < 0.05) were observed across most demographic subgroups except education. Higher mean intakes (mg/day) were seen in women aged ≥65 years (16.20), rural residents (16.38), light activity level (15.17), annual income > 100,000 CNY (15.51), manual laborers (16.11), and central China residents (highest, 21.01). Dried legumes and products, particularly tofu and its derivatives, contributed about 80% of total intake, with tofu-derived items accounting for 57.62–71.49%. Across all age groups, intake was significantly below the SPL, with >96% of participants failing to meet the recommendation. To reach the SPL, premenopausal women require ~40 mg/day supplemental SIF (equivalent to ~45 g soybeans/products), while perimenopausal and postmenopausal women require ~60 mg/day (~60 g soybeans/products). Conclusions: Dietary SIF intake among Chinese women ≥14 years is substantially below the SPL, a deficit that may attenuate associated health benefits. As dried beans and bean products are the dominant contributors, promoting these foods represents a feasible strategy to improve population-level SIF adequacy. Full article

The gut microbiota and its metabolites, as components of the gut–bone axis, play a pivotal role in regulating skeletal homeostasis through the bidirectional communication network. In this systematic review, evidence was collected from mainstream databases following standardized inclusion/exclusion criteria for screening, to comprehensively retrieve and screen eligible studies from multiple mainstream databases according to standardized inclusion and exclusion criteria, and systematically summarize current research progress on plant-derived bioactive compounds targeting the gut–bone axis for skeletal health regulation. This review systematically explores the underlying mechanisms of the gut–bone axis and critically evaluates the regulatory effects and therapeutic potential of plant-derived bioactive compounds. Particular attention is given to targeted interventions involving prebiotics, probiotics, synbiotics, and plant-rich diets or functional foods. Among these interventions, synbiotics represent the most successful strategy and show the most prominent therapeutic possibilities in bone-related disorders. Different from single prebiotics (only nourish endogenous intestinal microbes), individual probiotics (easy to be degraded in gastrointestinal tract with poor colonization) and ordinary plant-rich diets (unfixed effective dosage and weak targeting property), synbiotics combine prebiotic carriers and viable probiotic strains to produce complementary advantages, which is the core reason for its outstanding therapeutic prospect against bone diseases. Synbiotics exert synergistic effects on gut microecology, mineral absorption, and immune regulation, leading to more robust and consistent improvements in bone health than single prebiotics, probiotics, or general plant-rich diets. They have been verified in preclinical and clinical studies to ameliorate osteoporosis and related skeletal diseases via the gut–bone axis. These strategies offer novel insights into the prevention and treatment of bone metabolic disorders, such as osteoporosis, by targeting the gut–bone axis with phytochemicals. Key outcomes of this review include that synbiotics, soy isoflavones, naringin, curcumin, and resveratrol effectively improve bone mineral density, restore gut microbiota balance, and inhibit pathological bone resorption via the gut–bone axis. Collectively, the above bioactive substances realize bone protection mainly by reshaping gut flora, elevating mineral uptake and suppressing excessive osteoclast activity. Representative cases include soy isoflavones mitigating estrogen-deficient bone loss in OVX models, naringin improving the trabecular microarchitecture, and probiotic BL-11 promoting longitudinal bone growth in children. Future directions will focus on clarifying dose–response relationships, developing standardized synbiotic formulations, constructing microbiome-guided precision diets, and conducting large-sample randomized controlled trials to translate plant-derived compounds into clinical therapies. Full article

Daidzin is a soy-derived isoflavone with reported anti-obesity effects; however, the biological activity of microbial-derived daidzin remains poorly understood. In this study, we investigated the anti-adipogenic and anti-obesity potential of microbial-derived daidzin (hereafter referred to as Eco-3) in both in vitro and in vivo models. Eco-3 significantly suppressed adipocyte differentiation and lipid accumulation in 3T3-L1 preadipocytes and human adipose-derived stem cells (hASCs) without inducing cytotoxicity. Mechanistically, Eco-3 reduced the expression of key adipogenic regulators, including PPAR-γ and C/EBP-α, and modulated lipid metabolism-related proteins such as FAS and perilipin A. In addition, Eco-3 activated AMPK signaling while inhibiting the STAT-3 and STAT-5 pathway. In zebrafish models, Eco-3 significantly reduced lipid accumulation under both normal and diet-induced obesity conditions, as demonstrated by LipidGreen2 and Oil Red O staining. Collectively, these findings suggest that Eco-3 exerts anti-obesity effects through coordinated regulation of adipogenesis and lipid metabolism. Full article

Breast cancer is one of the leading causes of cancer incidence and mortality in many countries worldwide although there is considerable geographic variation. Diet is thought to impact risk of developing breast cancer but identifying specific dietary factors involved in the etiology of this disease has proven difficult. The two primary factors that initially led to an interest in soy are the historically low breast cancer incidence and mortality rates in Japan and the uniquely high concentration of isoflavones in soybeans and foods derived from this legume. Isoflavones bind to both estrogen receptors although preferentially to estrogen receptor-β. Prospective cohort studies indicate that isoflavone intake is associated with a reduced risk of developing breast cancer, but randomized controlled trials in which the impact of soy and isoflavones on markers of breast cancer risk has been evaluated are not supportive of this protective association. It may be that for isoflavones to reduce risk, intake needs to occur during childhood and/or adolescence. The notion that consuming soy early in life reduces risk of adult breast cancer, herein referred to as the “early soy intake hypothesis” (ESIH), was proposed >30 years ago. The results of rodent studies and retrospective observational studies that examined incidence and/or markers of breast cancer risk support the ESIH. However, a lack of randomized controlled trials precludes a clear recommendation for soy consumption during childhood and/or adolescence specifically for breast cancer prevention. Although soy foods provide high-quality protein and a variety of nutrients and can be part of a healthy diet for young and adolescent girls, more research is needed to advance the ESIH. Full article

Bioactive polyphenols are increasingly recognized as modulators of multiple biological processes relevant to human health and disease. Among these compounds, genistein, a soy-derived isoflavone, and butein, a naturally occurring chalcone, have been investigated for their anticancer, anti-inflammatory, and metabolic regulatory activities, primarily in in vitro and preclinical experimental models. Despite their distinct chemical structures, available evidence indicates that genistein and butein can influence key molecular pathways involved in cell survival, energy metabolism, and programmed cell death. Experimental studies have shown that these compounds may modulate PI3K/Akt and MAPK/ERK signaling, alter glycolytic and mitochondrial metabolism, and induce apoptotic responses through caspase activation and poly(ADP-ribose) polymerase cleavage. This review provides a comprehensive overview of the chemical characteristics, bioavailability, and proposed molecular mechanisms of action of genistein and butein, with a particular focus on their potentially convergent roles in metabolic reprogramming and apoptotic signaling networks. In addition, we discuss the conceptual basis for combination approaches involving these compounds, emphasizing systems-level pathway modulation rather than definitive pharmacological synergy. Importantly, many of the reported biological effects have been observed under experimental conditions using concentrations that may exceed physiologically achievable concentrations, thereby limiting direct extrapolation to clinical settings. Furthermore, the current evidence base is constrained by limited in vivo validation and a lack of robust clinical data, particularly for butein. Future studies are required to better define pharmacokinetic properties, physiological relevance, and context-dependent biological effects, thereby providing a more rigorous framework for future evaluation of the translational potential of genistein and butein. Full article

Background: Soy intake has been proposed as a protective factor for breast cancer, especially when exposure occurs early in life. Mammographic density (MD) is a strong predictor of breast cancer risk, but evidence linking soy intake at specific life stages to adult mammographic density remains limited. Objective: The objective of this study was to evaluate the associations between dietary soy intake at different life stages and MD in premenopausal Chinese women. Methods: Dietary soy intake was assessed using a validated soy food frequency questionnaire for the past 12 months and retrospectively for earlier life stages (childhood: 6–12 years; adolescence: 13–18 years; young adulthood: 20–34 years), with recall aided by a life history calendar. MD was measured from bilateral cranio-caudal mammograms using a standardized computer-assisted method. Multivariable regression models were used to evaluate associations between soy protein and isoflavone intake at different life stages and MD, adjusting for relevant confounders. Results: Among 815 premenopausal women (mean age 40.9 y), mean current soy protein and isoflavone intakes were 10.3 g/day and 22.0 mg/day, respectively. Soy intakes across life stages were moderately correlated (r = 0.33–0.81). After multivariable adjustment, soy protein intake during adolescence (β = −0.067, SE = 0.029, p = 0.023) and childhood (β = −0.071, SE = 0.032, p = 0.028) was significantly and inversely associated with adult MD. Young adult intake showed a non-significant inverse trend (β = −0.052, p = 0.075), and current intake showed no association (p = 0.93). Higher mean early-life (ages 6–18) and life course soy intakes were also inversely associated with MD (β range: −0.077 to −0.082; all p < 0.05). Women with consistently high early-life soy intake had 5.8–6.6% lower adjusted MD than those with consistently low intake. Conclusions: Early-life soy exposure may influence adult breast tissue composition and represents a potentially modifiable protective factor in breast cancer prevention. These findings carry important public health implications, particularly for populations experiencing dietary westernization. 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

Background/Objectives: Precocious puberty in girls currently appears to be one of the main problems in pediatric endocrine gynecology. Early onset of menstruation (EOM) means that the age at which the first menstruation occurs is lower than the average/median for the population, which ranges from 12 to 13 years and depends primarily on ethnic origin. Depending on age and severity of symptoms, these disorders negatively affect girls’ quality of life in many areas, including school life, family relationships, and everyday life. Methods: This article provides a scoping review summarizing scientific evidence from human studies on the association between substances derived from green tea (flavanols) and soy (isoflavones) and precocious puberty in girls. Results: Despite the relatively small number of girls enrolled in the studies, available scientific evidence from randomized controlled trials (RCTs) suggests that polyphenols from decaffeinated green tea (DGTP) may contribute to lowering the age of first menstruation in girls living with obesity. The effect of soy isoflavones or soy in the context of premature menstruation in girls is unclear. Most studies report that it may have no effect on the age of first menstruation, while individual studies suggest that very early exposure to soy (< 4 months of age) may result in earlier puberty, and others suggest that higher consumption of soy isoflavones delays this process. Conclusions: Further well-designed intervention studies in humans are needed to better understand the endocrine and metabolic relationships regarding the role and importance of specific polyphenols in the pathogenic mechanisms of the development and treatment of precocious puberty in girls. Full article

Estrogen suppress food intake, and soy isoflavones exhibit estrogen-like activities. However, the specific isoflavone components responsible for appetite regulation and their underlying neuroendocrine mechanisms remain unclear. We investigated whether the major soy isoflavones daidzein and genistein differentially influence feeding behavior and hypothalamic appetite-regulating neuropeptides in female rats. Ovariectomized (OVX) and sham-operated female rats were fed a control diet or diets supplemented with daidzein or genistein (150 mg/kg diet) for one or two weeks under ad libitum conditions. A separate OVX group received subcutaneous estradiol. Hypothalamic expression of orexigenic and anorexigenic neuropeptides was quantified during the dark (active) and light (inactive) phases. Daidzein, but not genistein, significantly reduced food intake, body weight gain, and body fat in both OVX and intact females, whereas estradiol decreased these parameters only in OVX rats. Among all hypothalamic neuropeptides examined, urocortin was the only gene that responded to dietary daidzein, showing a significant increase exclusively during the light phase of Week 1. Neither NPY nor CRH expression was altered by daidzein. The temporal pattern of urocortin induction closely paralleled the reduction in food intake, suggesting a potential mechanistic link. Daidzein exerts a female-specific anorectic effect that cannot be explained solely by estrogenic activity. The selective upregulation of hypothalamic urocortin during the light phase represents a novel neuroendocrine response to dietary daidzein and may contribute to its suppression of food intake. These findings provide new insight into the sex-specific metabolic actions of dietary isoflavones. Full article

As an isoflavone metabolite with diverse physiological activities, the development of efficient and sustainable manufacturing technologies for (S)-equol holds significant importance. This study focuses on the semi-rational design of daidzein reductase (DZNR), the first key enzyme in the (S)-equol biotransformation pathway. Through multiple sequence alignment and three-dimensional structural analysis, two critical residues, Gly30 and Ala105, were identified in DZNR. A library of single and combinatorial mutants was constructed and screened, yielding the double variant DZNR30S+105S with substantially enhanced catalytic performance. In a whole-cell biocatalytic system, the recombinant E. coli (Escherichia coli) strain harboring this combinatorial mutant achieved a yield of 238.3 mg/L (S)-equol at a substrate concentration of 1 mM daidzein, demonstrating markedly improved catalytic efficiency. Upon increasing the daidzein concentration to 2 mM, the reaction reached equilibrium within 5 h, producing 384.6 mg/L (S)-equol, which highlights the mutant’s excellent potential for high-substrate-concentration applications. This study not only provides novel mechanistic insights into DZNR catalysis but also successfully establishes a DZNR variant with enhanced activity, offering an efficient biocatalytic component for the industrial-scale biomanufacturing of (S)-equol and thereby advancing the development of green biosynthesis technologies for this valuable compound. Full article

Background/Objectives: Equol, a gut microbial metabolite of the soy isoflavone, daidzein, is associated with estrogenic activity and potential benefits for women’s health. While equol production depends on individual gut microbial composition, its dietary and clinical correlates in young women remain incompletely characterized. This study explored the relationship between urinary equol production, dietary habits, and premenstrual symptom severity in healthy university-aged women. Methods: We conducted a cross-sectional study of 41 Japanese women, aged 19–20 years. Urinary equol was measured using a validated liquid chromatography–tandem mass spectrometry (LC–MS/MS) method, following enzymatic hydrolysis. Participants were classified as either equol producers or non-producers, based on urinary concentration thresholds. Dietary intake was evaluated using a dietary questionnaire focused on soy products and dietary fiber sources. Premenstrual symptoms were assessed using a standardized Japanese questionnaire for premenstrual syndrome and premenstrual dysphoric disorder. Results: Twelve percent of participants were classified as equol producers. Compared with non-producers, equol producers reported higher consumption of pumpkin, soybean sprouts, and green tea. Among non-producers, higher consumption of certain vegetables and fiber-rich foods, including broccoli, pickled radish, konjac, and konjac jelly, was associated with greater premenstrual symptom severity, whereas such associations were not observed among equol producers. The analytical method demonstrated high sensitivity and reproducibility for urinary equol measurement. Conclusions: These findings suggest that equol production status may be associated with distinct dietary patterns and with differences in the relationship between food intake and premenstrual symptom severity in young women. Although the cross-sectional design and limited sample size preclude causal inference, these findings suggest that urinary equol is a promising candidate biomarker for future research on diet-related modulation of premenstrual symptoms. 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

Soy protein isolate (SPI)–soy isoflavone (SI) complexes were prepared via a pH-driven method at varying SI concentrations (0–7.0 mg/mL) to study their interactions and to analyze the structural and functional characteristics of the complexes. The findings showed that the SPI-SI complexes’ particle size first reduced and then rose with higher SI concentration. Fourier transform infrared spectroscopy revealed a reduction in β-sheet content (35.72%), indicating a limited structural rearrangement toward increased conformational flexibility. Consistently, fluorescence spectroscopy revealed that the fluorescence intensity of SPI diminished with the addition of SI, suggesting hydrogen-bond-mediated interactions. At 3.0 mg/mL SI, the complexes exhibited optimal physicochemical properties, with the most negative zeta potential (−29.78 mV), a solubility increase from 41.90% to 64.70%, and an elevated denaturation temperature from 86.77 °C to 88.79 °C, as well as 1.25-fold higher emulsifying capacity, and 1.86-fold greater emulsion stability; collectively establishing 3.0 mg/mL SI as the concentration where functional advantages are maximized. Overall, these findings demonstrate that pH-induced, non-covalent SPI-SI complexation effectively modulates protein conformation and interfacial properties, providing a green and effective approach for enhancing plant protein functionality in food systems. Full article

High-fat diets are commonly used in eel aquaculture to reduce protein costs, but excessive fat intake can impair intestine health. This study investigated whether soy isoflavones (SIFs), an emulsifying additive, could mitigate the negative effects of high-fat diets in eel. Six hundred eels (30.00 g) were randomly divided into four groups with three replicates: control (CK, 5.96% fat), high-fat diet (HFD, 11.96% fat), and HFD supplemented with 50 mg/kg (LSF) or 100 mg/kg SIF (HSF) for 8 weeks. Results show that SIF supplementation reversed adverse effects on eels fed high-fat diets, reducing intestine damage (better villi development and lower malondialdehyde levels) and improving antioxidant capacity (higher glutathione, p < 0.05). SIFs also increased key antioxidant-related enzyme activities (catalase, superoxide dismutase, p < 0.05). Gut microbiota analysis revealed that SIFs restored microbial balance by reducing Proteobacteria (Pseudomonas) and increasing Firmicutes (Lactococcus), while suppressing harmful metabolic pathways like lipopolysaccharide biosynthesis. These findings demonstrate that dietary SIFs (50 mg/kg) effectively counteract high-fat diet-induced intestine damage and gut dysbiosis in eels, offering a practical nutritional strategy for sustainable aquaculture. Full article