Search Results (85)

Background: Daidzein, a secondary metabolite primarily obtained from soybean (Glycine max L.) and other legumes, has significant nutritional and pharmacological value. Chemically, daidzein is an isoflavone and plays a crucial role in the therapeutic amelioration of numerous disorders, including allergies, inflammation, diabetes, cardiovascular, and neurodegenerative diseases. Emerging preclinical evidence suggests potential antineoplastic activity of daidzein against various cancers. This current work aims to perform a critical evaluation of daidzein’s potential as an anticancer molecule with an in-depth understanding of its mechanisms of action. Methods: The data for this review were obtained from various sources, including PubMed, Scopus, and Web of Science. Results: Daidzein, as a pure phytochemical or in combination with other phytochemicals and anticancer drugs, has been reported to induce apoptotic and autophagic cell death, impeding cell growth, viability, proliferation, and angiogenesis, and arresting cell division at various phases in vitro. Various daidzein formulations also exhibited similar anticancer effects by immunomodulation and genetic alteration in the cancer cells. In vivo anticancer studies of daidzein also suggest modulation of several hallmark pathways, such as inhibition of nuclear factor-κB, Janus kinase/signal transducer and activator of transcription, and rat sarcoma virus/rapidly accelerated fibrosarcoma. Conclusions: Irrespective of numerous promising preclinical studies, the absence of clinical studies provides a major challenge to establishing daidzein’s safety and efficacy in human cancers. Therefore, further advancements in clinical research of daidzein are vital for manifesting as an antineoplastic drug. Full article

Fermentation is a widely utilized technology that efficiently enriches bioactive compounds, thereby enhancing the bioactivity of food. This study aimed to investigate the release of the total polyphenol content (TPC) and flavonoid content (TFC), changes in antioxidant activity, and in vitro relative abundance trends of phenolic metabolites in the fermented composite juice of kidney beans and mulberries. An in vitro simulated gastric and intestinal digestion method was employed to examine the release patterns of polyphenols and flavonoids, along with alterations in antioxidant activity during the gastrointestinal digestion of the fermented composite juice. Non-targeted metabolomics LC-MS technology was employed to detect changes in the relative abundance and enrichment of phenolic metabolites during fermentation and digestion stages. The results indicated that after simulated digestion, the polyphenol content increased by 1.42-fold and the flavonoid content by 2.53-fold compared to pre-digestion. The scavenging rates for DPPH radicals, hydroxyl radicals, and ABTS radicals reached 85.44%, 94.77%, and 76.12%, respectively. Non-targeted metabolomic investigation through KEGG pathway enrichment showed associations between phenolic metabolites and antioxidant activity. During fermentation and digestion, daidzein, genistein, quercetin, and catechin may be the potential compounds contributing to the enhanced antioxidant activity of FBMJ. Among these, phenolic metabolites are significantly enriched in the biosynthetic pathways of flavonoids and flavanols. This study has elucidated the metabolic variations between the fermentation and digestion stages of fermented composite juice from a metabolomics perspective, providing preliminary in vitro research evidence and theoretical clues for developing it as a functional food with antioxidant potential. 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

Triple-negative breast cancer (TNBC) is a highly aggressive subtype with limited targeted therapies, underscoring an urgent need for novel agents. The soil-derived Streptomyces sp. CB00271, isolated from a biodiversity hotspot, was investigated for its bioactive metabolites. Bioassay-guided isolation led to the identification of actinolactomycin (1), alongside daidzein (2) and genistein (3). Remarkably, actinolactomycin (1) exhibited potent cytotoxicity against TNBC models, with IC₅₀ values of 0.72 ± 0.12 μM (MDA-MB-231) and 0.15 ± 0.02 μM (4T1), demonstrating approximately 9-fold and 31-fold greater potency than cisplatin, respectively, and suggesting action through targeted pathway inhibition. This study constitutes the first report to systematically highlight the exceptional anti-TNBC potential of this rare natural product, establishing it as a promising lead compound against this challenging subtype. Furthermore, Streptomyces sp. CB00271 is identified as a valuable and scarce microbial resource for actinolactomycin, providing a new avenue to address its supply limitation and facilitate future development. 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

Background: Numerous degenerative diseases are brought on by inflammation and oxidative stress. Metabolites from plants contain anti-inflammatory and antioxidant properties. Indigenous and understudied, Thottea sivarajanii is a significant ethnobotanical herb. It is native to the Western Ghats and belongs to the Aristolochiaceae family. Objectives: The current study investigated the antioxidant and anti-inflammatory properties of T. sivarajanii leaf methanol extract (TSL) and the insights provided by phytochemical analysis. Methods: The HRLC–MS/MS (Q-TOF) study is used for the phytochemical analysis. The antioxidant efficacy is evaluated in terms of DPPH and ABTS radical scavenging, and reducing power (FRAP assay). In vitro anti-inflammatory efficacy was evaluated on RAW 264.7 cells challenged with lipopolysaccharide (LPS). Result: The HRLC–MS/MS (Q-TOF) study indicated the presence of bioactive molecules such as ursolic acid, Daidzein 4’,7-diglucoside, Calophyllin B, and Berbamine, etc. The results showed in vitro antioxidant capacity in DPPH, and ABTS, radical scavenging, and ferric-reducing activities with respective IC₅₀ and EC₅₀ values of 184.5 ± 2.4, 24.15 ± 0.13, and 4.94 ± 0.32 µg/mL, respectively. LPS significantly stimulated the production of IL-1β, IL-6, and TNF-α in RAW 264.7 cells (p < 0.001). Treatment with TSL reduced levels of IL-1β and IL-6 from 776.1 ± 11.4 and 1678.1 ± 12.4 to 195.4 ± 9.2 and 465.4 ± 11.8 pg/mg protein. It also reduced NO levels from 91.4 ± 1.3 to 30.8 ± 1.7 µM/mg protein while reducing TNF-α levels from 2041.2 ± 15.1 to 1037.5 ± 15.4 pg/mg protein. Conclusions: This work contributes to the growing evidence supporting the pharmacological importance of the underexplored Thottea sivarajanii, highlighting this species as a promising candidate for natural antioxidant and anti-inflammatory agents. Full article

This study aimed to optimize a formulation of Spatholobus littoralis Hassk. stems and Sauropus androgynus L. leaves using Simple Lattice Design (SLD). In this context, the response variable was DPPH (2,2-Diphenyl-1-picrylhydrazyl) antioxidant activity, while the optimum extract concentration of the two plants served as the experimental factor. Subsequently, the optimum formula was investigated for its in vitro anti-inflammatory activity against COX-2 (cyclooxygenase-2) and through in silico study. Molecular docking on the COX-2 receptor (PDB ID: 5IKQ) from the secondary metabolite profile was validated for the optimum formula. The formulation recommended by SLD comprised a 1:1 mixture of 70% ethanol extract of S. littoralis Hassk. stems and S. androgynus L. leaves. This optimum formula had an IC₅₀ value of 108.70 µg/mL for the DPPH antioxidant with a synergistic effect due to the production of higher COX-2 inhibitory activity (73.05 ± 2.36%) than the single extract at 100 µg/mL. Daidzein (−8.514 kcal/mol), (10E,12Z)-9-Hydroperoxy-10,12-octadecadienoic acid (−7.604 kcal/mol), arteannuic acid (−7.114 kcal/mol), L-Proline,4-hydroxy-5-oxo-4-(tetrahydro-2,3,4-trihydroxy-2-furanyl)- (−6.480 kcal/mol), and Androst-2-en-17-amine,4,4-dimethyl-N-(2-phenylethyl)-, (5.alpha.)- (−5.440 kcal/mol) were the five compounds from the 70% ethanol extract of S. littoralis Hassk. stems and S. androgynus L. leaves that strongly bound 5IKQ. These compounds were obtained from five groups of compounds, namely flavonoids, fatty acids, terpenoids, amino acid derivatives, and amine derivatives. The formulation of S. littoralis Hassk. and S. androgynus L. extract has potential as an antioxidant and anti-inflammatory agent. Full article

Background: Steamed Panax notoginseng saponins (SPNSs) can alleviate cyclophosphamide-induced anemia. However, the hepatointestinal effects of SPNSs and their role in ameliorating cyclophosphamide-induced anemia remain unexplored. Objective: To elucidate the hepatointestinal effects of SPNSs and their role in ameliorating cyclophosphamide-induced anemia. Methods: Blood samples were collected and analyzed on days 7 and 14. Liver tissues and small intestinal villi structures were observed via HE staining. Liver and colon content metabolites were detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Liver proteins were analyzed by using an Orbitrap Astral mass spectrometer. Colon content microbiota composition was assessed via metagenomics. Signaling pathway protein expression was analyzed via Western blotting (WB). Results: SPNSs significantly increased the red blood cell (RBC) count and hemoglobin (HGB) level by day 14 and alleviated hepatointestinal damage. Hepatic metabolomics revealed: the most abundant metabolites were fatty acids and stachyose on day 7 and amino acid and arachidonic acid derivatives on day 14. KEGG analysis implicated cAMP signaling. Proteomics revealed upregulated immune-related proteins and enhanced PI3K pathway activity (WB-validated). Colon content metabolomics showed increased daidzein, 3-(2,5-dimethoxyphenyl) propanoic acid, γ-CEHC, and adenosine in SPNS groups on day 14. Metagenomics indicated differential abundances of Heminiphilus faecis, Phocaeicola sartorii, and s-bacterium_J10.2018 on day 14. Multiomics integration demonstrated significant correlations between hepatic metabolites, hematopoietic proteins, colon content metabolites, and probiotic bacteria. Conclusions: SPNS alleviates cyclophosphamide-induced hepato-intestinal injury in anemic mice by modulating the gut microbiota and enhancing hepato-intestinal immune defense. Additionally, SPNSs ameliorate anemia in cyclophosphamide-treated mice by activating the cAMP/PI3K/AKT pathway, promoting hepatocyte proliferation, and increasing hematopoietic protein expression. Full article

Background: Lophatheri Herba, a traditional East Asian herb with documented food uses, contains bioactive flavonoids. This study investigated how Aspergillus oryzae fermentation modifies its short-chain fatty acids (SCFAs) and metabolome, and evaluated the fermented product’s impact on intestinal barrier function in mice. Methods: Fermented leaf extracts were analyzed via GC-MS/LC-MS for SCFAs and metabolites. Forty-eight mice were divided into control (standard diet) and three experimental groups (25, 50, 100 mg/kg/day fermented product). After a 4-week intervention, duodenal morphology, colonic cytokines (IL-6/IL-1β), and cecal microbiota were assessed. Results: We identified significant SCFAs optimization. Significantly increased: acetic acid; butyric acid (p < 0.001); isobutyric acid (p < 0.01); isovaleric acid (p < 0.05). No significant change: propionic acid and isohexanoic acid. Significantly decreased: valeric acid and hexanoic acid (p < 0.001). Metabolomic remodeling showed (i) flavonoid pathway activation and (ii) key metabolite upregulation (daidzein, 4,7-dihydroxyflavone, 3,7-dimethylquercetin, aloe-emodin, soyasapogenol M1, etc.). Gut function peaked at 100 mg/kg with 18% higher duodenal villus height (p < 0.05), improved villus/crypt ratio, and reduced IL-6/IL-1β. Probiotic taxa including Lactobacillus, unclassified f__Lachnospiraceae, Dubosiella, and Monoglobus increased. Conclusions: Fermented Lophatheri Herba protects gut health through synergistic SCFAs optimization, flavonoid enrichment, and probiotic proliferation, supporting its potential as a microbiota-targeting functional food ingredient. Full article

Huperzine A (HupA) can alleviate Alzheimer’s disease due to its reversible inhibition of acetylcholinesterase (AChE). The chemical synthesis and plant extraction of HupA is plagued by route complexity and resource scarcity, respectively. Although some endophytic fungi from Huperzia serrata can independently biosynthesize HupA, their yields are trivial. After a comprehensive investigation of HupA-producing H. serrata across China, we focused on the endophytic fungi from Hunan and Hubei provinces, which demonstrated high-level HupA. Morphological characteristics and internal transcriptional sequence (ITS) analysis revealed their diversity. Among the four HupA-producing endophytic fungi, Colletotrichum kahawae is the best-performing and was thus subjected to fermentation optimization. When its fermentation medium was supplemented with H. serrata flavonoids daidzein and apigenin, HupA yields reached 58.38 μg/g (dry cell weight, dcw) and 72.21 μg/g dcw, respectively. In contrast, the addition of L-lysine and H. serrata extracts led to yields of 50.17 μg/g dcw and 255.32 μg/g dcw, respectively. Transcriptomic analysis revealed that H. serrata extracts substantially upregulated the expression of HupA biosynthesis genes in C. kahawae. Overall, H. serrata extracts outperformed L-lysine, daidzein, and apigenin in boosting HupA production, as they encompass all the necessary nutrients for C. kahawae growth. This study not only connotes a nutritional exchange between H. serrata and C. kahawae during long-term coevolution but also offers insights for harnessing plant extracts for the overproduction of desired metabolites in endophytic fungi. Full article

Objective: The aim of this work is to investigate the impact of exercise on gut microbiome composition, serum metabolites, and their correlation with osteoarthritis (OA) severity. Methods: Thirty-six Sprague-Dawley (SD) rats were randomly divided into four groups: Sham rats without treadmill walking (Sham/Sed group, n = 9), Sham rats with treadmill walking 2 months (Sham/TW2M group, n = 9), PTOA rats without treadmill walking (PTOA/Sed group, n = 9), and PTOA rats with treadmill walking 2 months (PTOA/TW2M group, n = 9). The PTOA model was induced by transection of the anterior cruciate ligament (ACLT) and destabilization of the medial meniscus (DMM). Histological evaluation and micro-CT analysis were performed to observe the pathological changes in cartilage and subchondral bone, respectively. Additionally, we conducted 16S rDNA sequencing of fecal samples and untargeted metabolomic analysis using liquid chromatography–mass spectrometry (LC–MS) of serum samples to detect the alteration of gut microbiota composition and metabolites. Results: Exercise effectively mitigated OA-related pathological changes, including articular cartilage degeneration and subchondral bone loss. Moreover, 16S rDNA sequencing analysis of gut microbiome revealed a decreased abundance of Bacteroidetes (p < 0.01), Bacteroidia (p < 0.01), Rikenellaceae (p < 0.01), [Paraprevotellaceae] (p < 0.01), and Paraprevotella (p < 0.01) but an increase in Firmicutes (p < 0.01) in PTOA/TW2M group rats compared with PTOA/Sed group as a response to exercise. In addition, the results of metabolomics analysis showed that exercise treatment contributed to the upregulation of Daidzein and Anthranilic acid and downregulation of 1-Palmitoyllysophosphatidylcholine. Moreover, the correlation analysis showed that Rikenellaceae significantly positively correlated with both OARSI (r = 0.81, p < 0.01) and Mankin score (r = 0.83, p < 0.01) and negatively correlated with the serum level of Anthranilic acid (r = −0.56, p < 0.01) and Daidzein (r = −0.46, p < 0.01). Conclusions: Exercise can effectively mitigate OA through slowing down articular cartilage degeneration and subchondral bone loss, modulating gut microbiota composition, and increasing beneficial metabolites. Full article

Plant hormones play a critical role in the physiological and biochemical mechanisms of plants, with functions such as regulating the metabolic pathways of secondary metabolite production and alleviating external stresses. In this study, the synthesis of flavonoids in black soybean sprouts was induced by slight acid combined with the plant hormones abscisic acid (ABA) and melatonin (MT). The results indicated that the contents of daidzin, genistin, daidzein, and genistein in black soybean sprouts treated with slight acid were increased by 10 μM ABA and 75 μM MT, and the total flavonoid content was significantly enhanced. Compared with the slight acid treatment, the H₂O₂ and malondialdehyde (MDA) contents in black soybean sprouts were increased after ABA treatment, and the black soybean sprouts were further stressed. However, the H₂O₂ and MDA contents in black soybean sprouts were significantly decreased after MT treatment, indicating that the stress of black soybean sprouts can be alleviated by MT. Under slight acid stress, the genes related to flavonoid synthesis in black soybean sprouts were induced by exogenous ABA, promoting the accumulation of flavonoids; under exogenous MT treatment, the activity of phenylpropanoid metabolism enzymes was significantly increased, the genes related to flavonoid synthesis were upregulated, and flavonoid synthesis was induced. These results suggest that the combination of slight acid and plant hormone treatments promotes the accumulation of flavonoid substances during the germination of black soybeans. This research lays the foundation for improving the growth conditions of black soybeans and promoting the enrichment of flavonoid substances in black soybeans. Full article

Background: Sarcopenic obesity, which is associated with a poorer prognosis than that of sarcopenia alone, may be positively affected by soy isoflavones, known inhibitors of muscle atrophy. Herein, we hypothesize that these compounds may prevent sarcopenic obesity by upregulating the gut metabolites with anti-inflammatory effects. Methods: To explore the effects of soy isoflavones on sarcopenic obesity and its mechanisms, we employed both in vivo and in vitro experiments. Mice were fed a high-fat, high-sucrose diet with or without soy isoflavone supplementation. Additionally, the mouse C2C12 myotube cells were treated with palmitic acid and daidzein in vitro. Results: The isoflavone considerably reduced muscle atrophy and the expression of the muscle atrophy genes in the treated group compared to the control group (Fbxo32, p = 0.0012; Trim63, p < 0.0001; Foxo1, p < 0.0001; Tnfa, p = 0.1343). Elevated levels of daidzein were found in the muscles and feces of the experimental group compared to the control group (feces, p = 0.0122; muscle, p = 0.0020). The real-time PCR results demonstrated that the daidzein decreased the expression of the palmitate-induced inflammation and muscle atrophy genes in the C2C12 myotube cells (Tnfa, p = 0.0201; Il6, p = 0.0008; Fbxo32, p < 0.0001; Hdac4, p = 0.0002; Trim63, p = 0.0114; Foxo1, p < 0.0001). Additionally, it reduced the palmitate-induced protein expression related to the muscle atrophy in the C2C12 myotube cells (Foxo1, p = 0.0078; MuRF1, p = 0.0119). Conclusions: The daidzein suppressed inflammatory cytokine- and muscle atrophy-related gene expression in the C2C12 myotubes, thereby inhibiting muscle atrophy. Full article