Search Results (334)

Thai fermented soybeans (TFSs) contain phytochemicals with anti-diabetic benefits. In this study, an initial non-optimized TFS extract (TFSE) was prepared using a conventional triplicate 80% ethanol extraction method and evaluated for its biological activity. TFSE effectively reversed TNF-α-induced insulin resistance in 3T3-L1 adipocytes by enhancing insulin-stimulated glucose uptake, indicating anti-diabetic potential. TFSE also upregulated the phosphorylation of AKT (a key insulin signaling mediator) and the expression of adipogenic proteins (PPARγ, CEBPα) in TNF-α-exposed 3T3-L1, suggesting the mitigation of adipocyte dysfunction; however, the results did not reach statistical significance. The conventional extraction process was labor-intensive and time-consuming, and to enhance extraction efficiency and bioactivity, the process was subsequently optimized using environmentally friendly microwave-assisted extraction (MAE) in combination with the Box–Behnken design (BBD) and response surface methodology (RSM). The optimized extract (O-TFSE) was obtained over a significantly shorter extraction time and exhibited higher levels of total flavonoids and antioxidant activity in comparison to TFSE, while showing reduced levels of isoflavones (daidzein, genistein, and glycitein) in relation to TFSE. Interestingly, O-TFSE retained similar efficacy in reversing TNF-α-induced insulin resistance and demonstrated significantly stronger α-glucosidase and α-amylase inhibitory activities, indicating its enhanced potential for diabetes management. These results support the use of MAE as an efficient method for extracting functional compounds from TFS for functional foods targeting insulin resistance and type 2 diabetes mellitus. Full article

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

Skeletal muscle atrophy is a debilitating condition characterized by the loss of muscle mass and function. It is commonly associated with aging, chronic diseases, disuse, and prolonged glucocorticoid therapy. Oxidative stress and catabolic signaling pathways play significant roles in the progression of muscle degradation. Despite its clinical relevance, few effective therapeutic options are currently available. In this study, we investigated the protective effects of an ethanolic extract of Glycine Semen Preparata (GSP), i.e., fermented black soybeans, using in vitro and in vivo models of dexamethasone (Dexa)-induced muscle atrophy. In C2C12 myoblasts and myotubes, GSP significantly attenuated both oxidative stress-induced and Dexa-induced damages by reducing reactive oxygen species levels and by suppressing the expression of the muscle-specific E3 ubiquitin ligases MuRF1 and Atrogin-1. Moreover, GSP upregulated key genes involved in muscle regeneration (Myod1 and Myog) and mitochondrial biogenesis (PGC1α), indicating its dual role in muscle protection and regeneration. Oral administration of GSP to mice with Dexa-induced muscle atrophy resulted in improved muscle fiber integrity, increased proportion of large cross-sectional area fibers, and partial recovery of motor function. Isoflavone aglycones, such as daidzein and genistein, were identified as active compounds that contribute to the beneficial effects of GSP through antioxidant activity and gene promoter enhancement. Thus, GSP is a promising nutraceutical that prevents or mitigates muscle atrophy by targeting oxidative stress and promoting myogenesis and mitochondrial function. Further studies are warranted to standardize the bioactive components and explore their clinical applications. 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

Wild soybean (Glycine soja, GS) is a traditional medicine used to treat inflammation. In this study, the anti-atopic properties of GS leaf and stem extract on skin inflammation were evaluated in the Dermatophagoides farinae-extract-induced mouse model and keratinocytes. Oral administration of the GS extract reduced scratching, dermatitis score, transepidermal water loss, thickness of epidermis, inflammatory cell accumulation, and serum concentrations of thymic stromal lymphopoietin and immunoglobulin E. GS downregulated the expression of inflammatory gene markers of atopic dermatitis (AD), including interleukin (IL)-6; regulated on activation, normal T cell expressed and secreted (RANTES); thymus- and activation-regulated chemokine (TARC); and macrophage-derived chemokine (MDC) and upregulated the expression of filaggrin, a keratinocyte differentiation marker, in skin tissue. GS downregulated Janus kinase 1, signal transducer and activation of transcription (STAT) 1, and STAT3 pathways. Using ultra-performance liquid chromatography, we identified seven flavonoids in GS extract, including apigenin, epicatechin, genistein, genistin, daidzin, daidzein, and soyasaponin Bb. GS, apigenin, and genistein reduced the expression of IL-6, MDC, TARC, and RANTES and increased filaggrin via the downregulation of STAT3 phosphorylation in interferon-γ/tumor necrosis factor-α-stimulated keratinocytes. Our results suggest that GS leaf and stem extract ameliorates AD-like skin inflammation by regulating the immune response and restoring skin barrier function. Full article

The renin–angiotensin system helps regulate the endocrine system in modulating blood pressure, fluid volume, and body fluid electrolyte levels. The disruption of the renin–angiotensin system can lead to kidney disease onset and progression. However, the mechanism by which kidney angiotensinogen expression and secretion induce the onset and progression of diabetic nephropathy remains unclear. In this study, we used renal proximal tubular epithelial cells, which express high levels of angiotensinogen, to examine food components that regulate angiotensinogen secretion. The renal proximal tubular epithelial cells were first treated with catalase (antioxidant), daidzein, equol (an isoflavone), a MAP kinase inhibitor, ERK, p38, or JNK and then stimulated with hydrogen peroxide. After 24 h, we collected a culture medium to perform an enzyme-linked immunosorbent assay test for angiotensinogen and cells in order to perform real-time PCR to detect angiotensinogen. We found that angiotensinogen secretion increased as the hydrogen peroxide concentration increased. Catalase, daidzein, and equol decreased angiotensinogen expression and secretion. To investigate the cell signaling mechanism involved in these effects, we assessed the contribution of the MAP kinase cascade. Our data suggest the contribution of p38 and JNK. Our study shows that, in proximal tubular epithelial cells, hydrogen peroxide stimulates angiotensinogen secretion. Isoflavones and p38 inhibited angiotensinogen secretion. Full article

The purpose of this study was to examine the effect of daidzein on the proliferation of porcine mammary epithelial cells (PMECs) and elucidate the underlying molecular mechanisms. PMECs were treated with varying daidzein or rapamycin levels, and then cell proliferation and mTOR pathway protein expression were detected. When the concentration of daidzein added was in the range of 0–80 μM, cell proliferation was significantly promoted (p < 0.05). These results were in agreement with those obtained using the 5-ethynyl-2′-deoxyuridine (EdU) assay. Daidzein administration at 20 and 40 μM concentrations triggered significant activation of the mTOR signaling cascade and enhanced expression of downstream cell-cycle-regulatory proteins (cyclin D1) (p < 0.05). Moreover, exposure to 40 μM daidzein attenuated apoptotic signaling, as evidenced by reduced levels of Bax protein and cleaved caspase-3 (p < 0.05). These effects were reversed when rapamycin was used to inhibit the mTOR pathway. In conclusion, our findings suggest that daidzein activates PMEC proliferation via the mTOR pathway. The present work not only characterizes new functional properties of daidzein but also establishes mechanistic evidence supporting its role in augmenting sow lactation efficiency. Full article

The solid-state fermentation (SSF) of agro-industrial by-products such as okara, pomegranate peel, and cranberry pomace presents a sustainable approach to enhance the release of bioactive compounds. This study investigated the effects of different microbial cultures—Rhizopus oligosporus, Aspergillus oryzae, Streptococcus thermophilus, and a co-culture of R. oligosporus and S. thermophilus—on the bioconversion of bioactive compounds in 100% okara, okara with 2% pomegranate peel, and okara with 1% cranberry pomace. The objective was to assess whether co-culture fermentation with molds and S. thermophilus augments the release of bioactive compounds in okara-based fermentations through synergistic enzymatic activity. Over a period of 72 h, isoflavone transformation (daidzin, daidzein, genistin, and genistein), pH evolution, and water activity were assessed. The co-culture system exhibited improved bioconversion, leading to significant (p < 0.01) increases in daidzein and genistein in pure okara compared to the starting material. The highest polyphenol content (0.908 mg/g) and antioxidant capacity (24.9 mg Trolox eq/g) were recorded in 100% okara. However, pomegranate peel inhibited β-glucosidase activity, delaying the release of isoflavone aglycones. These findings confirm that co-culture fermentation is an effective strategy for enhancing the bioactive properties of okara-based fermentations. This facilitates the release of bioactive aglycones and supports the upcycling of agro-industrial by-products into functional food ingredients. Future research should focus on optimizing fermentation parameters to further enhance the release of bioactive compounds. Full article

Ultraviolet B (UVB) radiation is a key factor contributing to photodamage in epidermal cells. This study investigated the protective effects of Thua Nao, a Thai fermented soybean product, against UVB-induced damage in human epidermal keratinocytes (HaCaT) and the underlying mechanisms. Thua Nao extract fractions were prepared using a solvent partition method. We found that the dichloromethane fraction (TN-DC), along with its isoflavones daidzein and glycitein, significantly protected against UVB-induced HaCaT cell death. This protection involved inhibiting caspase-9 and caspase-3 activation, thus preventing apoptosis. Additionally, treatment with TN-DC, daidzein, and glycitein suppressed the UVB-induced production of inflammatory mediators, including interleukin-6 (IL-6), IL-8, inducible nitric oxide synthase, and cyclooxygenase-2. These protective effects were associated with reduced intracellular reactive oxygen species and enhanced the levels of antioxidant enzymes, including superoxide dismutase and glutathione peroxidase 4. Signaling pathway analysis revealed that TN-DC activated the pro-survival ERK1/2 and Akt pathways while decreased the phosphorylation of JNK in UVB-exposed cells. On the other hand, daidzein and glycitein enhanced ERK1/2 activation and reduced the phosphorylation of JNK and p38 MAPKs. The involvement of ERK1/2 and Akt activation in cell survival was confirmed using specific inhibitors. Thus, TN-DC and its isoflavones protects keratinocytes from UVB-induced oxidative damage and inflammation by modulating MAPKs and Akt signaling. Full article

Solar radiation is crucial for intercropping, while partial shading can protect intercropped soybean leaves from irradiation damage during the pod-ripening period under high solar radiation. This study explored the leaf dynamics and soybean quality for the maize–soybean system, for monoculture soybean (MS), monoculture maize (MM), two-row maize + three-row soybean (IS2-3), and four-row maize + four-row soybean (IS4-4). The results revealed that soybean leaves under IS2-3 and IS4-4 treatments showed increases in Rubisco activity of 59.8% and 12.4% compared with MS, respectively. The antioxidant capacity in soybean leaves in MS was higher than that under intercropping treatments. Soybean leaves under IS2-3 and IS4-4 exhibited higher alpha and beta diversities in their endophytes compared with MS. The relative abundance of pathotrophs under IS2-3 was reduced by 19.1% and 22.6% compared to that of those under MS and IS4-4, respectively. The total land equivalent ratio (LER) under IS2-3 was more than 1.00, and increased by 6.4% and 15.7% compared with IS4-4 in 2023 and 2024, respectively. Soybean seeds under IS2-3 and IS4-4 showed 4.1% and 4.2% increases in crude protein content compared to those of MS, respectively. Among various biosynthesis and metabolism processes, flavone and flavonol biosynthesis exerted a stronger influence on soybean seeds in MS, IS2-3, and IS4-4. Soybean seeds under IS2-3 showed elevated genistein content and reduced daidzein content compared with those of MS. Intercropping soybean treatments, especially IS2-3, maintained leaf health during the pod-ripening period and enhanced the crude protein content compared with sole soybean treatment, thus guiding the design of intercropping in areas with high solar radiation. Full article

Cancer, a worldwide problem and one of the leading causes of death due to uncontrolled cell proliferation, can be caused by various factors, such as genetic and environmental factors. Apoptosis is a programmed cell death mechanism that eliminates abnormal cells or renews cells. There are two main apoptotic pathways: intrinsic and extrinsic pathways. These pathways can be affected by various signaling pathways in cancer, such as the PI3K/AKT, MAPK, Wnt, and JAK/STAT pathways. Numerous approaches to cancer treatment have been studied, and among them, natural compounds have been actively researched. Flavonoids are natural compounds from fruits and vegetables and have been studied for their anti-cancer effects. Isoflavones, one of the subclasses of flavonoids, are usually found in soy food or legumes and are effective in several bioactive functions. The well-known isoflavones are genistein, daidzein, and glycitein. Irigenin and iridin can be extracted from the Iris family. Both irigenin and iridin are currently being studied for anti-inflammation, antioxidant, and anti-cancer by inducing apoptosis. In this review, we summarized five isoflavones, genistein, daidzein, glycitein, irigenin, and iridin and their effects on three different cancers: breast cancer, prostate cancer, and gastric cancer. Full article

Background: Cuscuta australis R. Br. is a parasitic herbaceous plant that obtains nutrients by forming specialized structures called haustoria to invade host plants. Methods: In this study, we elucidated the differences in the gene expression regulation and metabolic characteristics between Cuscuta australis and Glycine max (Glycine max (L.) Merr. Var Williams) through comprehensive transcriptomic and metabolomic analyses. Results: The results demonstrated significant differences in the gene expression and metabolic features between the haustorium and the distal stem segments. The differentially expressed genes absorbed by Cuscuta australis from the soybean host influence amino acid metabolism, and the expression of the S-adenosylmethionine decarboxylase gene may affect the production of 5′-methylthioadenosine. A high expression of the chalcone synthase enzyme could lead to an increased daidzein content. Many Glycine max genes were also integrated into Cuscuta australis within the haustorium. Conclusions: This study systematically analyzed, for the first time, the significant differences in gene expression and metabolic characteristics between the haustoria and distal stem segments of Cuscuta. It also explored the nutrient absorption mechanisms of the host plant. Additionally, the research discovered that Cuscuta can absorb a substantial amount of host genes and adapt to its parasitic lifestyle through differential gene expression and metabolic changes. These findings provide important insights into the parasitic mechanisms of Cuscuta australis and lay the foundation for the development of effective control strategies. Full article

Mutations in the tumor suppressor genes BRCA1 and BRCA2 are associated with the triple-negative breast cancer phenotype, particularly aggressive and hard-to-treat tumors lacking estrogen, progesterone, and human epidermal growth factor receptor 2. This research aimed to understand the metabolic and genetic links behind BRCA1 and BRCA2 mutations and investigate their relationship with effective therapies. Using the Cytoscape software, two networks were generated through a bibliographic analysis of articles retrieved from the PubMed-NCBI database. We identified 98 genes deregulated by BRCA mutations, and 24 were modulated by therapies. In particular, BIRC5, SIRT1, MYC, EZH2, and CSN2 are influenced by BRCA1, while BCL2, BAX, and BRIP1 are influenced by BRCA2 mutation. Moreover, the study evaluated the efficacy of several promising therapies, targeting only BRCA1/BRCA2-mutated cells. In this context, CDDO-Imidazolide was shown to increase ROS levels and induce DNA damage. Similarly, resveratrol decreased the expression of the anti-apoptotic gene BIRC5 while it increased SIRT1 both in vitro and in vivo. Other specific drugs were found to induce apoptosis selectively in BRCA-mutated cells or block cell growth when the mutation occurs, i.e., 3-deazaneplanocin A, genistein or daidzein, and PARP inhibitors. Finally, over-representation analysis on the genes highlights ferroptosis and proteoglycan pathways as potential drug targets for more effective treatments. Full article

Background/Objectives: Isoflavone (ISO) may have immunosuppressive and promoting effects. In this study, we aimed to examine the association between maternal dietary ISO intake during pregnancy and childhood allergic rhinoconjunctivitis at the age of 3 years using the Japanese Birth Cohort data. Methods: Overall, 78,549 mother–child pairs were studied. Maternal dietary ISO intake (the sum of genistein and daidzein) during pregnancy was evaluated using a food frequency questionnaire. Information on physician-diagnosed allergic rhinoconjunctivitis was collected from the caregiver-reported questionnaire. After classifying ISO intake into quartiles (Q1: reference), multivariable logistic regression analysis was employed to explore the association with allergic rhinoconjunctivitis. Results: No association was observed between maternal ISO intake and allergic rhinoconjunctivitis in any child. However, in the sex-stratified analysis, maternal ISO intake linked to allergic rhinoconjunctivitis in female children positively (Q2, adjusted odds ratio [aOR]: 1.22, 95% confidence interval [CI]: 1.06–1.40; Q3, aOR: 1.17, 95% CI: 1.01–1.35; Q4, aOR: 1.24, 95% CI: 1.07–1.44). Conclusions: Maternal dietary ISO intake during pregnancy was sex-specifically linked to childhood allergic rhinoconjunctivitis in children. These findings provide insights into the need for estimating the optimal ISO consumption during pregnancy for allergy avoidance in children. Full article