Search Results (993)

Background: Cibotium barometz (L.) J. Sm. is a medicinal fern whose rhizome is the sole officinal part, while roots, stems, leaves and young shoots are discarded as agricultural residues. The chemical rationale for this restriction, and the value of the discarded organs, remain undefined. Materials and methods: Here, untargeted LC–MS/MS metabolomics (UHPLC–Orbitrap) of methanol/acetonitrile/water extracts was applied to five organs of C. barometz (three pooled biological replicates per organ), annotating 2765 polar-to-moderately-polar metabolites. Results: Organ identity dominated the metabolic architecture of the sampled population: the first two principal components separated all five organs, with leaf and root as the two mutually opposed metabolic extremes and stem, young shoot and rhizome forming a contiguous module. Exploratory pairwise OPLS-DA combined with FDR-controlled univariate criteria yielded 193–1223 differentially accumulated metabolites per comparison, and tissue-specificity analysis assigned 2031 metabolites (73.45%) predominantly to a single organ. Discussion: Metabolite accumulation patterns along the phenylpropanoid–flavonoid pathway was spatially partitioned, with flavan-3-ols and isoflavones accumulating in root, flavone/flavonol glycosides in leaf and predominantly hydroxycinnamic acids in rhizome and young shoot. Of 22 previously reported or candidate quality control constituents, putatively annotated terpenoid lactones were detected almost exclusively in the rhizome, whereas several phenolics showed markedly higher relative abundance in root or leaf. Conclusions: These relative-abundance data indicate that the non-officinal organs are chemically complementary potential resources; absolute quantification, bioactivity and safety evaluation are prerequisites before any medicinal valorisation. Full article

The kombucha symbiotic culture of bacteria and yeast (SCOBY) is a multispecies microbial consortium distributed between cell-containing fermentation liquid and a cellulose-rich pellicle. Here, “kombucha SCOBY” denotes the viable consortium delivered through either compartment or both compartments. Dominated by fermentative yeasts and acetic acid bacteria, the consortium produces ethanol and organic acids and biotransforms phenolic compounds, enabling fermentation beyond conventional sweetened teas. This review critically evaluates studies in which viable consortia directly fermented food matrices. In dairy systems, kombucha-derived inocula acidify milk and induce casein gelation, although more slowly than yogurt starters, and kombucha broth has also supported fresh cheese production. In soy-based matrices, fermentation converts isoflavone glucosides to aglycones, and fermented soy whey can coagulate tofu. Applications have also been reported in fruit and vegetable juices, agro-industrial by-products, botanical infusions and breadmaking. However, microbial composition and performance vary with the inoculum source, propagation history, and storage. Strain-defined preserved starters remain unvalidated in non-tea matrices, and potential hazards include mycotoxin formation and post-production ethanol accumulation. Therefore, standardized, comprehensively characterized, and matrix-specific starters are required for safe and reproducible translation across food matrices. Full article

Porcine reproductive and respiratory syndrome virus (PRRSV) has become a global health threat for swine. Because of the limited effectiveness of commercial vaccine strategies and the absence of specific antiviral chemical drugs for PRRS, it is urgent to identify new strategies for preventing and controlling PRRSV infections. Genistein, a soy-derived isoflavone, has shown promise in reducing viremia in PRRSV-infected pigs. However, its antiviral molecular mechanism remains unclear. This study investigates the inhibitory effects and mechanism of genistein on PRRSV infection in vitro. Our results demonstrated that genistein dose-dependently inhibited PRRSV infection in Marc-145 cells at several stages of the PRRSV replication cycle. With its favorable safety profile and potent efficacy in antiviral and growth promotion in swine, genistein stands out as a promising dietary adjunct for PRRSV prevention and control in swine husbandry. Full article

Postmenopausal osteoporosis (PMOP) is a metabolic bone disease driven by estrogen deficiency and a major contributor to fragility fractures, yet long-term use of current antiresorptive and anabolic agents remains constrained by tolerability and adherence. Plant-derived bioactive compounds—including flavonoids, isoflavones, curcuminoids, and stilbenes—show bone-protective activity in ovariectomized (OVX) models but share common delivery barriers: poor aqueous solubility, low oral bioavailability, rapid metabolic clearance, and limited skeletal targeting. Conventional nanonization improves systemic pharmacokinetics but cannot by itself address the spatial heterogeneity of skeletal target sites. This review focuses on surface-engineered phytochemical nanomedicines, in which mineral-affinity, cell-affinity, and pathology-responsive modules are introduced at the carrier interface to enhance bone-associated distribution, local retention, and microenvironment-responsive release. Organized around nanocarrier platforms, it summarizes cross-platform surface/interfacial engineering strategies and discusses how whole-body, ex vivo, and bone-section imaging can be combined with quantitative exposure assessment, micro-computed tomography (micro-CT), bone turnover markers, and histology to characterize carrier- or probe-associated distribution, spatial localization, and therapeutic performance, respectively. It then considers translational issues, including formulation reproducibility, ligand-density effects, model relevance, and long-term safety. The review aims to provide a framework for surface-engineered phytochemical strategies and a reference approach for multimodal, imaging-based evaluation of therapeutic outcomes. Full article

Background/Objectives: ShenRongGuBenHuanShao Pill (SRGBHSP) is a traditional Chinese medicine (TCM) used for the treatment of erectile dysfunction (ED). However, its active constituents and pharmacological mechanisms remain unclear. This study characterized the flavonoid constituents of SRGBHSP and investigated its effects on HC-associated ED-related alterations and potential molecular mechanisms using an integrated multi-omics strategy. Methods: SRGBHSP constituents were characterized by UPLC-Q-TOF-MS/MS, and representative flavonoids were quantitatively analyzed by UPLC-MS/MS. Rats exposed to HC received SRGBHSP (1.08, 2.16, or 4.32 g/kg), Yougui Pill, or sildenafil concurrently with HC administration. Pharmacological effects were evaluated using APO-induced erectile responses, histopathology, sperm quality, reproductive hormones, oxidative stress indices, and serum NO/GC/cGMP-related parameters. Integrated 16S rRNA sequencing, untargeted metabolomics, transcriptomics, and DIA-based proteomics were combined with RT-qPCR and Western blotting to investigate potential regulatory mechanisms. Results: A total of 131 flavonoids were characterized in SRGBHSP, including flavones, isoflavones, flavonols, flavanones, chalcones, flavans, anthocyanidins, and aurones. Quantitative analysis identified baicalin as the predominant flavonoid constituent. APO-induced erection frequency decreased from 3.50 ± 1.29 in the control group to 0.50 ± 0.58 in the model group and increased to 4.50 ± 1.29 following high-dose SRGBHSP intervention. SRGBHSP also improved reproductive hormone homeostasis, sperm quality, and oxidative stress status in HC-treated rats. SRGBHSP increased serum NOS, NO, GC, and cGMP levels and increased the mRNA and total protein expression of PI3K, Akt, and mTOR in penile tissue. Integrated multi-omics analyses revealed coordinated alterations in gut microbiota, glycerophospholipid metabolism, and penile transcriptomic and proteomic profiles. Conclusions: SRGBHSP attenuated multiple ED-related alterations associated with HC exposure, accompanied by improvements in reproductive function, oxidative stress status, and serum NO/GC/cGMP-related parameters. Integrated multi-omics analyses together with expression-level validation revealed coordinated alterations in gut microbiota, glycerophospholipid metabolism, and PI3K/Akt/mTOR-related molecules following SRGBHSP intervention. These findings suggest the potential involvement of PI3K/Akt/mTOR-related signaling in the response to SRGBHSP, although its activation status and causal contribution remain to be established. Flavonoids may represent important bioactive constituents associated with the observed effects of SRGBHSP. Overall, this study provides an integrated pharmacological and multi-omics framework for understanding the effects of SRGBHSP on HC-associated ED-related alterations. Full article

Localized phytochemical formulations may provide complementary strategies for controlling mucosal colonization by Streptococcus agalactiae and Streptococcus pyogenes, but computational prioritization requires orthogonal biological validation. This study integrated molecular docking against the redox-sensing transcriptional repressor Rex of S. agalactiae and a protein tyrosine phosphatase target of S. pyogenes (SP-PTP) with in vitro broth microdilution, biofilm, target-bridging, and epithelial-tolerance experiments. Isoflavone showed the most favorable natural-compound interaction with Rex (ΔG = −8.3 kcal/mol), whereas secoisolariciresinol diglucoside (SDG) led the natural-ligand ranking for SP-PTP (ΔG = −5.2 kcal/mol). The complete formulation produced MIC50 values of 0.031% and 0.063% v/v against S. agalactiae and S. pyogenes, respectively; inhibited biofilm formation by 89.2% and 80.1%; and preserved >92% epithelial viability at 1× MIC. Among the three natural candidates with complete matched broth data, target-normalized docking and composite MIC50/MIC90/MBC50 ranks were perfectly concordant in both species; pooled species-stratified Spearman analysis yielded ρ = 1.000 (exact p = 0.0556; n = 6). In contrast, the extended panel including antibacterial comparators showed negligible concordance (ρ = 0.081; p = 0.7826; n = 14). Principal component analysis assigned 74.8% of variance to an in vitro potency axis and 24.6% to a largely orthogonal docking axis. Thus, the experiments confirmed the target-specific ordering of the natural candidates but did not support extrapolation of docking rank across mechanistically heterogeneous antibacterial classes. Intracellular target inhibition, genetic causality, and component synergy remain unestablished. Full article

Cigarette smoke exposure is a major preventable risk factor for respiratory disease and drives oxidative and inflammatory lung injury, highlighting the urgent need for safe, multi-target interventions beyond conventional anti-inflammatory therapy. Formononetin (FMN), a naturally occurring isoflavone with antioxidant, anti-inflammatory, and microbiota-modulating potential, may offer a dietary-botanical strategy against smoke-related pulmonary damage. This study evaluated FMN against cigarette smoke extract (CSE)-induced lung injury and explored its associations with intestinal barrier integrity, gut microbiota, taurine metabolism, SLC6A6 expression, and NF-κB activation. In a CSE-challenged mouse model, oral FMN, particularly at 70 mg/kg, improved body weight gain, reduced the lung index, attenuated pulmonary histopathological injury, restored GSH/GSSG and SOD, decreased MDA, and suppressed TNF-α, IL-1β, and IL-6 expression. FMN also ameliorated colonic injury and restored ZO-1 and occludin expression. Exploratory 16S rRNA sequencing and fecal metabolomics indicated FMN-associated alterations in gut microbial composition and metabolic profiles, with taurine and hypotaurine metabolism identified as a candidate pathway for further investigation. FMN further restored lung taurine content and SLC6A6 expression while inhibiting NF-κB activation. These findings suggest that FMN alleviates CSE-induced lung injury and that this improvement is associated with coordinated changes in gut microbiota composition, taurine metabolism, SLC6A6 expression, and NF-κB activation. Full article

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

Dietary polyphenols are studied as potential adjuncts for type 2 diabetes (T2D), although many reviews still rely on an antioxidant framework that does not adequately reflect human exposure. This review organises the evidence around two metabolite waves, namely early postprandial phase-II conjugates produced by host enzymes within 0 to 4 h of a polyphenol-rich meal, and microbiome-derived catabolites including urolithins and γ-valerolactones that peak at 6 to 24 h. This biphasic interpretation is advanced as a hypothesis-generating framework rather than as an established explanation, and it offers a testable account of why polyphenol effects may be meal-contingent, metabotype-dependent and heterogeneous across clinical trials. Using randomised controlled trials and meta-analyses published between 2015 and 2025, we review the human evidence for anthocyanins, catechins, stilbenes, cocoa flavanols and olive phenolics, with briefer coverage of isoflavones, curcuminoids and ellagitannins. Anthocyanins show the most consistent glycaemic signal, with a best available pooled estimate of about 0.3% for HbA1c (−0.31%, median exposure eight weeks) derived from trials that did not verify metabolite exposure, an effect that is modest and lies at the lower bound of what is generally regarded as clinically meaningful. Green tea catechins and high-phenolic extra-virgin olive oil are associated with comparable postprandial gains, whereas cocoa flavanols and resveratrol more reliably improve vascular and inflammatory intermediates than glycaemia itself. Most interventions were well tolerated at the nutritional doses tested. Polyphenols are better regarded as meal-timed dietary adjuncts to standard T2D care than as primary glycaemic agents. Full article

This study investigated the combined administration of raffinose (RAF) and isoflavones (ISO) to enhance ISO bioavailability and alleviate high-fructose (HF)-induced liver damage. Mice were administered 20% HF water with RAF, ISO, or their combination (RAF + ISO) for 10 weeks. UPLC-qTOP/MS analysis showed that RAF + ISO significantly increased total ISO levels in serum, urine, and feces by 18.5%, 37.4%, and 13.6%, respectively, compared to ISO alone (p < 0.05). The combined treatment more effectively reduced HF-induced weight gain, visceral fat accumulation, and dyslipidemia, partly through suppression of FAS and ACC gene expression (p < 0.05). Furthermore, RAF + ISO more efficiently attenuated hepatic oxidative stress, inflammation, and insulin resistance than either agent alone. Liver enzyme activities (AST, ALT, ALP) were significantly reduced by RAF + ISO treatment, consistent with histopathological improvements in liver tissue. These findings demonstrate that RAF enhances the systemic availability of ISO and potentiates its protective effects against HF-induced metabolic and hepatic alterations. Full article

Coat color is closely associated with the nutritional and functional properties of mung bean (Vigna radiata L.) seeds. However, the relationship between the coat color and efficiency in nutrients of mung bean seeds has not been clearly clarified. In this study, comparative metabolomic analysis, bioactive compounds’ content measurement, and antioxidant capacities’ (ABTS⁺, DPPH, FRAP) determinations were conducted on four distinct varieties with different seed coat colors (black: BL, yellow: YE, yellow-green: YG, green: GR). A total of 1544 metabolites were identified in these mung bean seeds, with amino acids and derivatives, flavonoids, phenolic acids, lipids, and terpenoids, as the top five classes with high relative signal abundance. BL was abundant in flavonoids (20.12%), flavonols, anthocyanins (with six anthocyanins accounting for 22.32–565.21-fold of that in other varieties), free fatty acids, and phenolic acid. YE accumulated more amino acids and derivatives (31.85%), isoflavones (with daidzein accounting for 1.97–9.34-fold of other varieties), flavones, and lignans/coumarins. Antioxidant capacity determination results showed that BL exhibited the strongest FRAP (p < 0.05), YG had the highest DPPH scavenging activity (p < 0.05), while YE showed numerically the highest ABTS⁺ scavenging capacity (p > 0.05). Notably, anthocyanin accumulation was positively correlated with FRAP, while isoflavone and amino acid accumulations were positively correlated with ABTS⁺ scavenging capacity. These findings suggested that the overall antioxidant activity of mung bean seeds was jointly regulated by multiple metabolite classes. This study elucidates seed metabolomic variations among mung bean varieties, providing insights for functional breeding and precision food development. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disorder characterized by chronic hyperglycemia, oxidative stress, protein glycation, low-grade inflammation, and dysregulation of signaling pathways, including those involving nuclear factor kappa B (NF-κB). Isoflavones from Fabaceae species exhibit diverse biological activities and may represent multifunctional candidates for addressing the interconnected mechanisms underlying T2DM. This study performed a consensus in silico pharmacodynamic screening of twelve representative Fabaceae isoflavones to prioritize compounds with predicted antiglycating, deglycating, antidiabetic, antioxidant, and NF-κB-related anti-inflammatory activities. Methods: Twelve representative Fabaceae isoflavones were evaluated using a multimethod computational workflow. Antiglycating and deglycating activities were predicted using IT Microcosm, antidiabetic and hypoglycemic activities were assessed using Prediction of Activity Spectra for Substances (PASS), antioxidant potential was evaluated using similarity-based prediction and quantum-chemical calculations, and NF-κB-related anti-inflammatory activity was investigated using similarity-based prediction combined with molecular docking. Molecular docking was applied specifically to the NF-κB-related anti-inflammatory analysis and did not contribute to the hypoglycemic/antidiabetic prediction. The individual predictions were integrated using a consensus scoring strategy to prioritize compounds across multiple pharmacodynamic domains. Results: The investigated isoflavones demonstrated moderate but broad predicted multifunctional activities. Malonylgenistin, biochanin A, and formononetin showed the most favorable predicted antiglycating profiles. Genistin, acetyldaidzin, acetylglycitin, and puerarin ranked highest in terms of predicted antidiabetic activity, whereas genistein exhibited the strongest predicted antioxidant profile. Daidzin and genistin received the highest integrated NF-κB-related computational rankings, although these predictions apply to intact glycosides rather than their expected in vivo hydrolysis products. Conclusions: This study presents a consensus computational framework for the comparative prioritization of Fabaceae isoflavones based on their predicted multifunctional pharmacodynamic profiles. The results provide a rational basis for selecting candidate compounds for future biochemical, cell-based, pharmacokinetic, and in vivo investigations, although it is emphasized that the present findings are based exclusively on computational predictions and require experimental validation. Full article

Background/Objectives: Pseudomonas aeruginosa is a notorious multidrug-resistant pathogen that causes serious acute and chronic infections by employing quorum sensing (QS)-regulated virulence, biofilm formation, and host-damaging inflammation. To overcome the yield limitation of two previously identified marine secondary metabolites with dual QS inhibitory and PPAR-γ agonistic activities, we further screened marine-derived natural products for more abundant candidates with similar anti-virulence and anti-inflammatory properties. Methods: In this study, isoflavones were evaluated for anti-QS and PPAR-γ transactivation activities using reporter gene assays, and for antibacterial, anti-virulence, and anti-inflammatory effects via broth microdilution, biofilm, G. mellonella infection, and ELISA cytokine assays. Results: Daidzein and genistein were selected for their optimal anti-QS and PPAR-γ activation activities. They inhibited a key QS regulator and suppressed pyocyanin production and biofilm formation in P. aeruginosa without affecting bacterial growth, indicating minimal selective pressure for resistance. In addition, daidzein and genistein were found to synergistically sensitize the wild-type P. aeruginosa strain to gentamicin, carbenicillin, tobramycin, ampicillin, and polymyxin B, and synergistically or partially synergistically sensitize a multidrug-resistant strain to gentamicin, tobramycin, and ampicillin. Moreover, a Galleria mellonella infection model confirmed that daidzein and genistein significantly enhance the efficacy of gentamicin against P. aeruginosa infection in vivo. Furthermore, in host macrophages, daidzein and genistein significantly inhibited LPS-induced production of NO, IL-6, and IL-1β when combined with an RXR agonist, implying a protective effect on host tissues through PPAR-γ activation. Conclusions: These findings demonstrate that daidzein and genistein serve as effective adjuncts to conventional antibiotics, exerting multifaceted actions against P. aeruginosa infection. Full article

Carboxylesterases (CXEs) participate in diverse plant metabolic processes, including isoflavone biosynthesis. However, the soybean GmCXE subfamily remains poorly characterized, especially in relation to root isoflavone accumulation and the response to Fusarium oxysporum. Here, fifty-six putative GmCXE genes were identified in the soybean genome and classified into three major phylogenetic clades. Analyses of gene structure, conserved motifs, protein domains, and promoter cis-elements revealed conserved features as well as potential functional divergence among subfamily members. Collinearity and duplication analyses indicated that segmental duplication was the main driver of GmCXE subfamily expansion. Tissue-specific expression profiling and RT-qPCR validation selected five root-expressed genes as candidates associated with isoflavone accumulation. SNP variation analysis and allelic group analysis of 209 soybean accessions further prioritized GmCXE54 as a candidate gene for root isoflavone accumulation. Allelic groups defined by a putative promoter SNP, Chr.20-rs39215413, showed significant differences in root daidzein and total isoflavone contents, with accessions carrying the C allele exhibiting higher levels of both traits than those carrying the T allele. Functional analysis in soybean hairy roots showed that GmCXE54 overexpression increased daidzein and total isoflavone accumulation. At 3 h after F. oxysporum inoculation, GmCXE2, GmCXE39, and GmCXE54 were induced, with GmCXE54 showing the strongest response in the resistant accession ZD27. These findings clarify GmCXE subfamily evolution and identify GmCXE54 as a candidate gene associated with root isoflavone accumulation and early F. oxysporum response, offering new perspectives for improving soybean isoflavone-related traits and investigating root response mechanisms. Full article