Search Results (2,758)

Introduction: Altered lipid metabolism is implicated in atrial fibrillation, but longitudinal lipidomic changes during anticoagulation remain poorly characterized. Objectives: To characterize plasma lipidomic changes during 12 weeks of edoxaban treatment and explore associated metabolic pathways in Chinese patients with nonvalvular atrial fibrillation (NVAF). Methods: This prespecified substudy of a prospective multicenter study analyzed fasting predose plasma collected at baseline and week 12 from 74 patients receiving protocol-assigned edoxaban doses (15 mg, n = 3; 30 mg, n = 23; 60 mg, n = 48). Widely targeted UPLC-MS/MS lipid profiling, with laboratory quality control (QC CV < 30%), yielded 1099 lipid features retained for statistical analysis. Differential lipids were defined by paired testing with Benjamini–Hochberg correction (|log₂FC| > 0.58 and q < 0.05). Results: The overall, 30 mg, and 60 mg analyses identified 25, 15, and 35 FDR-significant features, respectively; none was significant in the exploratory 15 mg group. Twelve features were shared across the primary analyses and increased at week 12; they comprised mainly acylcarnitines, together with docosadienoic acid and DG (21:0/16:0/0:0), and four lacked HMDB identifiers. The corresponding FDR panels yielded participant-grouped out-of-fold AUCs of 0.918 (95% CI 0.890–0.963), 0.786 (0.701–0.890), and 0.891 (0.835–0.950) for discriminating baseline from week 12, respectively. Pathway mapping identified no multi-compound enriched pathways (q < 0.05). Observed annotations represented single-metabolite signals—most notably DG (21:0/16:0/0:0) (HMDB0094301) and octanoylcarnitine (HMDB0000791)—rather than coordinated, pathway-level alterations. Conclusions: Paired analyses identified consistent longitudinal plasma lipidomic changes in patients receiving edoxaban. The 12 shared features provide focused candidates for targeted validation. Controlled studies are needed to determine whether these changes are specific to edoxaban and to establish their biological and clinical relevance. Full article

Six Centaurea cyanus L. flower extract variants were prepared using methanol, ethanol or water as a solvent; in each case, the material was either defatted with chloroform or not. The phytochemical profile of all obtained extracts was analyzed qualitatively and quantitatively using UPLC-PDA-Q/TOF-MS. In total, 35 phenolic compounds were detected, including flavonols, flavones, anthocyanins, phenolic acids and their derivatives, as well as an N-p-coumaroyl spermidine derivative; some compounds were identified using authentic standards, while others were tentatively identified based on chromatography and mass spectrometry data. The defatted ethanolic extract showed the highest total quantified phenolic content (42.18 mg/g DW), with the predominant constituents being apigenin derivatives, particularly apigenin-O-hexoside-O-glucuronide and apigenin-3-O-glucoside-(6″-acetyl)glucoside. The extract exhibited notably high antioxidant capacity, viz. DPPH (240.34 µmol TE/g), ABTS (170.53 µmol TE/g), and FRAP (189.93 µmol TE/g), and moderate antimicrobial activity, particularly against E. coli (MIC 0.5 mg/mL). The extract did not exhibit any cytotoxic effect toward L929 or Hs68 fibroblasts in vitro at concentrations up to 5 mg/mL. These findings indicate that the phenolic-rich ethanolic extract demonstrated both antioxidant and antimicrobial activities while also being non-cytotoxic against fibroblasts within the tested concentration range; as such, it may be suitable for dermatological and cosmetic formulations. Full article

Fritillariae Cirrhosae Bulbus (Chuanbeimu) is a high-value traditional Chinese medicine with significant botanical diversity. While extensive research has focused on its alkaloid components, the global lipidome, which is vital for plant stress adaptation and signaling, remains largely unexplored. This study employed untargeted lipidomics via UPLC-Q-TOF-MS to characterize the lipid profiles of three dominant cultivated materials: Fritillaria unibracteata, F. cirrhosa, and F. unibracteata var. wabuensis. A conserved qualitative lipidome encompassing 311 lipid species was identified across all samples. Interestingly, Fritillaria bulbs exhibited a uniquely “precursor-rich” profile dominated by free fatty acids (37.23–47.12%) and phosphatidic acids (6.19–11.33%), highlighting extensive lipid turnover potentially influenced by both alpine environmental adaptation and post-harvest processing. Chemometric analyses revealed that despite qualitative similarities, the three cultivated groups possessed highly distinct quantitative lipid phenotypes. A panel of 97 differentially accumulated lipids was identified, among which specific triacylglycerols (TAGs) and fatty acid esters of hydroxy fatty acids (FAHFAs) exhibited the most pronounced stepwise variations. Pathway analysis highlighted significant variations in glycerolipid and glycerophospholipid metabolism among the specific sample groups. By acknowledging the confounding effects of specific agricultural microclimates and post-harvest factors, this exploratory study provides the first comprehensive phytochemical baseline for the Fritillaria lipidome, offering novel insights into their biochemical diversity and providing structural candidates for future targeted research into their adaptive lipid remodeling and pharmacological potential. Full article

Background: Euryale ferox Salisb. seed (Euryales Semen) is a traditional Chinese medicine whose therapeutic application is modulated by wheat bran stir-frying, a process that enhances its effects on tonifying the spleen and kidney. The molecular mechanisms and alterations in bioactive components underlying this processing-enhanced efficacy remain to be fully elucidated. This study aimed to systematically investigate the impact of wheat bran stir-frying on the metabolite profile of Euryales Semen and to reveal its potential pharmacological mechanisms. Methods: An integrated strategy combining UPLC-MS/MS-based metabolomics, network pharmacology, and molecular docking was employed. First, differential metabolites between raw and processed Euryales Semen were identified and quantified. Second, a “metabolite-target-disease” network was constructed to predict core targets and pathways. The docking protocol was validated by re-docking of co-crystallized ligands, with all RMSD values below 2.0 Å. Finally, molecular docking was used to predict the binding interactions between key metabolites and potential protein targets. Results: A total of 1597 metabolites were identified, and 244 were defined as differentially expressed (VIP > 1, |log2(FC)| ≥ 1). Processing significantly upregulated 19 of the 22 key metabolites identified, with Urolithin B showing the most dramatic increase (168-fold), which was identified with Level 1 confidence using an authentic standard. Network pharmacology analysis identified 10 core targets (e.g., MMP2, MMP9, AKR1B1) primarily associated with tumors, diabetes, and other chronic diseases. Molecular docking predicted strong binding affinities (<−9.0 kcal·mol⁻¹) between these core targets and key upregulated metabolites, including Urolithin B, Tangeretin, and Syringetin. Conclusions: This study suggests that wheat bran stir-frying fundamentally reshapes the metabolic profile of Euryales Semen, leading to the enrichment of bioactive metabolites (e.g., Urolithin B) and suggesting a potential for enhanced tonifying, anti-tumor, and anti-diabetic activities that warrants further experimental investigation. The dramatic increase in the content of Urolithin B, a metabolite not commonly found in plants, raises the hypothesis of a processing-induced chemical transformation, which warrants further experimental validation, and highlights its potential as a critical component for the herb’s efficacy. The findings offer a preliminary computational basis for understanding traditional processing practices, linking traditional knowledge with modern scientific evidence. Full article

Background/Objectives: Guizhi Fuling Capsule (GZFL), a Traditional Chinese Medicine (TCM) formula, is widely used for primary dysmenorrhea and other blood-stasis gynecological disorders. This study aimed to characterize its material basis, elucidate its multi-component, multi-target mechanism against acute primary dysmenorrhea, and establish an integrated pharmacokinetic-pharmacometabolomic-pharmacodynamic (PK-PM-PD) framework for TCM efficacy evaluation. Methods: GZFL constituents and serum metabolites in an oxytocin-/estradiol-induced rat dysmenorrhea model were characterized by UPLC/Q-TOF-MS. Uterine effects of GZFL-containing serum were assessed ex vivo. The active components of GZFL were screened by Chinmedomics, with candidate targets investigated through network pharmacology, transcriptomics, and molecular docking. In total, 23 pharmacodynamic indicators were integrated by principal component analysis into an Efficacy Index (EI). Correlation analysis between pharmacometabolomic and pharmacodynamic data yielded a Metabolite-Efficacy Index (MEI), evaluated across a 21-day time course. Results: Among 197 constituents characterized in GZFL extract, 136 serum-exposed components were detected, with several key metabolites enriched via biotransformation. GZFL-containing serum bidirectionally regulated uterine contractility toward the control level. Integrated analyses revealed 68 candidate therapeutic targets. GZFL suppressed NF-κB/IKKβ signaling, down-regulated COX-2/iNOS, restored the PGF2α/PGE2 balance, and normalized inflammatory cytokines. Eleven efficacy-associated metabolites correlated with pharmacodynamic recovery were revealed and integrated, with MEI achieving the highest predictive performance among five integration strategies (AUC = 0.9) and robustly tracking the full 21-day disease-recovery trajectory. Conclusions: GZFL attenuates dysmenorrhea through coordinated regulation of inflammation, prostaglandin metabolism, and uterine functional homeostasis, rather than through inhibition of a single target. The PK-PM-PD framework, with EI and MEI, offers a reproducible paradigm for evaluating complex TCM therapies. Full article

Inocutis levis (I. levis) is a rare edible and medicinal macrofungus with a traditional history of consumption as a dietary supplement and functional food raw material. However, the material basis and molecular mechanisms underlying its anti-breast cancer activity remain unclear. The present work aimed to systematically investigate the anti-proliferative activity of WYS, an active mycelial fraction isolated from I. levis, against MCF-7 breast cancer cells and to explore its underlying mechanisms. Firstly, 152 metabolites were putatively annotated in the WYS fraction via ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) combined with database matching. Through an integrated strategy combining network pharmacology and multi-algorithm machine learning screening, four core metabolites (dihydroartemisinin, cortisol, cinnamic acid, and guanosine) and five hub targets (CDK1, EGFR, TOP2A, FGF2, and KIT) were prioritized. Furthermore, 100 ns molecular dynamics simulations and molecular docking predicted favorable binding affinities between the core metabolites and their cognate target proteins and predicted that the anti-breast cancer effect of WYS may be associated with the regulation of cell cycle progression, mitochondrial apoptosis, and the MAPK signaling pathway. Subsequent in vitro functional assays validated that WYS inhibited the proliferation of MCF-7 cells in both dose- and time-dependent fashions, triggered G2/M phase arrest and intrinsic mitochondrial apoptosis, and inhibited the EGFR/MEK/ERK signaling axis, exhibiting limited cytotoxicity toward normal HUVEC cells. In vivo, WYS dose-dependently attenuated xenograft tumor growth, and its modulatory effects on cell cycle, apoptosis, and related signaling pathways were consistent with the in vitro observations. This study provides the first evidence that I. levis mycelial fraction WYS modulates EGFR/MEK/ERK-related signaling and induces G2/M cell cycle arrest, thereby exerting anti-proliferative and pro-apoptotic effects on MCF-7 breast cancer cells, providing a scientific basis for further investigation of I. levis as a functional food. Full article

Background/Objectives: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, and ginger contains phenolic constituents with anti-inflammatory potential. This study evaluated the antiarthritic efficacy of ginger ethanolic extract (GE) and explored its potential mechanisms through integrated pharmacological and computational approaches. Methods: GE was prepared by 70% ethanol reflux extraction and administered to adjuvant-induced arthritis (AIA) rats, with methotrexate as a positive control. Body weight; paw swelling; arthritis index; spleen index; and serum interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) were measured. Chemical profiling was performed by ultra-performance liquid chromatography–quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS), followed by network pharmacology, molecular docking, and molecular dynamics (MD) simulation. Results: GE attenuated paw edema, arthritis index elevation, splenic enlargement, and elevated serum inflammatory mediators in AIA rats. UPLC-Q-TOF-MS/MS annotated 38 constituents, mainly gingerols, shogaols, gingerdiones, gingerdiols, and related phenolic derivatives. Network analysis identified 217 overlapping ginger- and RA-associated targets, with TNF, IL6, and matrix metalloproteinase 9 (MMP9) prioritized among inflammatory and matrix-remodeling nodes. Docking and MD simulations supported stable predicted interactions for 8-gingerol-TNF and 6-gingerol-MMP9. Conclusions: GE showed antiarthritic activity in AIA rats. The integrated chemical, in vivo, and computational data suggest that ginger phenolics may modulate inflammatory mediators and candidate RA-related pathways; however, these mechanisms remain exploratory and require histological, tissue-level, and molecular validation. Full article

Background: Flavonoid secondary metabolites accumulate in xylem during heartwood formation and critically influence wood color and economic value. However, the distribution patterns of individual flavonoids across sapwood, transition zone, and heartwood remain poorly characterized in Castanopsis hystrix, limiting mechanistic understanding of heartwood formation and rational resource utilization. Methods: Sapwood, transition zone, and heartwood samples were collected and analyzed using ultra-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry (UPLC-QE-MS) for qualitative and quantitative flavonoid determination. Multivariate statistical approaches, including hierarchical clustering, principal component analysis (PCA), and orthogonal partial least-squares discriminant analysis (OPLS-DA), were applied to compare regional metabolic profiles and to identify characteristic differential markers. Results: A total of 26 flavonoids were identified, covering flavones, flavonols, flavanones, dihydroflavonols, and flavanols. Quantitative and cluster analyses revealed distinct region-preferential accumulation: dihydrorobinetin, dihydromyricetin, morin, and kaempferol were highly enriched in heartwood; fustin, taxifolin, and cyanidin predominated in the transition zone, whereas afzelin and astilbin were more abundant in sapwood. PCA and OPLS-DA further selected four characteristic markers, namely dihydromyricetin, dihydrorobinetin, kaempferol and (−)-epicatechin, that effectively discriminated the three regions. Conclusions: This study establishes a clear radial gradient of flavonoid accumulation in C. hystrix xylem, demonstrating selective enrichment of specific metabolites from sapwood to heartwood. These findings provide essential data for deciphering the biochemical mechanisms of heartwood formation and offer a metabolic basis for quality assessment and high-value utilization of this timber species. Full article

Ehretia macrophylla fruit is a traditionally used but underutilized functional resource that is noted for its diverse phytochemical composition, which includes flavonoids and polyphenols. However, the systematic metabolic transformations that occur in the fruit during post-harvest storage—particularly those associated with its traditional processing into dark fruit tea—remain largely unknown, limiting efforts to optimize quality and processing strategies. In the study, to address this gap, we employed a widely targeted metabolomics approach based on ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) to dynamically profile the fruit metabolome across four storage stages (T0, T4, T8, T12). A total of 1101 metabolites were putatively annotated, and day 8 (T8) emerged as a potential pronounced metabolic inflection point. From T8 onward, 30–40% of metabolites showed differential accumulation, characterized by a gradual rise in nutrition-relevant lipids, amino acids, and vitamins. In contrast, key antioxidant-related metabolites, including phenolics and flavonoids, increased transiently before T8 but declined sharply thereafter. These coordinated shifts correlated with an increased representation of lipid- and alkaloid-related metabolic pathways, whereas flavonoid-associated features showed a relative decline. Collectively, these findings provide insights into the biochemical processes potentially associated with fruit blackening and the marked decline in antioxidant capacity during traditional processing. Our study provides the first metabolic blueprint connecting traditional processing practices with phased metabolic remodeling, offering a scientific foundation for quality assessment and the development of informed post-harvest strategies for processing E. macrophylla fruit. Full article

(1) Background: Mosquitoes represent major vectors of human pathogens, and their control remains a global public health priority. However, the widespread use of synthetic insecticides has resulted in environmental contamination, adverse effects on non-target organisms, and the rapid emergence of insecticide resistance. These limitations have intensified the search for sustainable botanical alternatives. (2) Methods: The present study investigated the phytochemical composition and larvicidal efficacy of flower extracts from Chrysanthemum cinerariaefolium and Oenothera biennis, alongside their nanoemulsion formulations, against the third-instar larvae of Culex pipiens. Larvicidal assays demonstrated that nanoemulsion formulations markedly enhanced bioactivity compared with conventional extracts. (3) Results: After 48 h of exposure, C. cinerariaefolium nanoemulsion exhibited the strongest toxicity (LC₅₀ = 26.63 ppm), followed by methanol (44.46 ppm), hexane (73.90 ppm), and aqueous extracts (209.99 ppm). Corresponding LC₅₀ values for O. biennis were 31.89, 80.15, 140.69, and 393.22 ppm, respectively. Biochemical analyses indicated that C. cinerariaefolium treatments strongly inhibited detoxification and digestive enzymes (esterases, GABA-T, amylase, and lipase) and suppressed antioxidant defenses (SOD, GST, CAT, and GSH). This was accompanied by a significant elevation of oxidative stress biomarkers, including lipid peroxidation and protein carbonylation. In contrast, O. biennis induced comparatively moderate biochemical responses. The phytochemical profiling utilizing GC-MS revealed the identification of forty-nine and fifty volatile components from the C. cinerariaefolium (CW-Hex) and O. biennis (BOF) n-hexane extracts, respectively, primarily consisting of oxygenated hydrocarbons, fatty acids, and their esters. Furthermore, UPLC-MS/MS-assisted profiling of methanol, ethyl acetate, and aqueous extracts identified thirty-eight metabolites for CW and thirty-one for BOF. The CW extracts were predominant in flavonoids and fatty acids while also containing cinnamic acid derivatives, phenolic acids, diterpenoids, triterpenoids, pyrethrins, phenyl ethanoids, steroids, aurones, and tannins. BOF extracts were particularly rich in flavonoids, followed by fatty acids, cinnamic acid derivatives, tannins, and steroids. (4) Conclusions: These findings demonstrate that plant-derived formulations of C. cinerariaefolium, particularly in nanoemulsion form, exert potent larvicidal activity through the disruption of metabolic and antioxidant pathways, offering a promising eco-friendly strategy for vector control. Full article

The guarana seed peel (GSP), an agroindustrial waste, was characterized for its chemical composition and evaluated for its antimicrobial activity as a potential source of antibacterial compounds for wastewater disinfection using UPLC-QTOF-MS analysis. UPLC-QTOF-MS analysis of GSP, its raw extract (GSPE), and its purified extract (GSPP) identified 36 compounds, including catechin and its oligomers: a B-type procyanidin dimer, pavetannin B6 (trimer), and cinnamtannin A2 (tetramer). Principal component analysis (PCA) separated GSPE from GSPP along PC2, and the purification step concentrated flavonoids—mainly catechin and its oligomers—in GSPP. Antimicrobial activity was assessed against the human pathogens Escherichia coli and Salmonella typhimurium, causing gastroenteritis and invasive disease, and Staphylococcus aureus, causing skin and invasive infections. In real wastewater, GSPE (500 mg L⁻¹) reduced total coliforms by up to 81 ± 7% and E. coli by up to 74 ± 7% within 180 min. Confocal microscopy with the LIVE/DEAD^® BacLight™ kit (Thermo Fhisher, Eugene, OR, USA) confirmed loss of membrane integrity in GSPE-treated Escherichia coli, and disc diffusion with GSPP produced inhibition zones of 9–11 mm against Staphylococcus aureus, Escherichia coli and Salmonella typhimurium at 5 mg per disc. These results show that guarana seed peel—currently discarded—is a viable source of catechin-rich antibacterial extracts for wastewater disinfection. Full article

Evodia rutaecarpa is a valuable medicinal plant, yet its non-medicinal tissues remain largely underexplored. Here, we integrated ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)-based widely targeted metabolomics and RNA sequencing (RNA-seq) transcriptomics to systematically profile the metabolic and transcriptional landscapes of roots, stems, leaves, and flowers of Evodia rutaecarpa (Juss.) Benth. Our aim was to characterize tissue-specific metabolic differentiation and its underlying transcriptional regulatory mechanisms. Metabolomic analysis, employing principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) with robust model parameters (R²Y > 0.9, Q² > 0.5), identified 3090 differential metabolite features (variable importance in projection, VIP > 1.0; p < 0.05) across the four tissues, which exhibited distinct tissue-specific clustering patterns. Integrated Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and weighted gene co-expression network analysis (WGCNA) revealed that roots specifically accumulated quinolone alkaloids and flavonoid glycosides, accompanied by the coordinated upregulation of genes involved in flavonoid and phenylpropanoid biosynthetic pathways. In contrast, stems, leaves, and flowers were enriched in indole alkaloids (evodiamine and rutaecarpine) and volatile oil precursors, with concurrent upregulation of genes involved in tryptophan metabolism and indole alkaloid biosynthesis (e.g., tryptophan decarboxylase, TDC; s N-methyltransferase, NMT). Notably, leaves and flowers displayed particularly high accumulation levels of these bioactive alkaloids, suggesting their potential as alternative sources for industrial and pharmaceutical applications. WGCNA further identified multiple transcription factors and structural gene modules tightly correlated with evodiamine accumulation, offering promising candidate regulators for future biosynthetic pathway engineering. Collectively, this multi-omics integration study systematically elucidates the tissue-partitioned secondary metabolism of Evodia rutaecarpa (Juss.) Benth. and provides a solid scientific foundation for full-plant resource utilization, targeted development of non-medicinal tissues, and future metabolic engineering of indole alkaloid production. Full article

Background: Primary dysmenorrhea (PD) is a prevalent gynecological condition that significantly compromises the quality of life in adolescents and women of reproductive age. Within traditional Chinese medicine (TCM), Cold Coagulation and Blood Stasis Primary Dysmenorrhea (CCBS-PD) represents the most frequently observed syndrome pattern of PD. Wenjing Decoction (WJD), a classical TCM formulation, has been extensively employed for the treatment of CCBS-PD. However, given the multi-component and complex nature of WJD, the potential mechanisms underpinning its therapeutic effect have yet to be elucidated. Methods: A rat model of CCBS-PD was induced through ice-water bath stimulation in conjunction with estradiol benzoate and oxytocin. The pharmacological effects of WJD were evaluated by writhing response, hemorheological parameters, uterine index, histopathological examination, and biochemical assays. Serum-exposed constituents of WJD were characterized using UPLC-Orbitrap Exploris 120 MS. To study the mechanisms of WJD, methods from network pharmacology, molecular docking, and off-target metabolomics were used. Western blot analysis examined representative proteins in the signaling pathways predicted by network pharmacology. Network pharmacology and metabolomics were integrated to construct a pathway–metabolite–target–compound network, and representative targets were analyzed by RT-qPCR. Results: WJD treatment reduced writhing responses, improved hemorheological abnormalities, and alleviated uterine pathological changes in CCBS-PD rats. Serum pharmacochemistry identified 62 WJD-derived constituents. Metabolomics analysis indicated that WJD was associated with alterations in nitrogen metabolism, valine/leucine/isoleucine biosynthesis and arginine biosynthesis. Network pharmacology and molecular docking suggested several candidate compounds and targets, including Robinetin, Levistolide A, Pratol, 7,4′-dihydroxyflavone, EGFR, AKT1, ESR1, MMP9, MAPK3, and TNF. RT-qPCR showed that selected genes, including AKT1, EGFR, MAPK3, TNF, ESR1, MMP9 and CASP3, were changed in the model group and partially restored following WJD improvement. Western blot analysis demonstrated that WJD treatment decreased the phosphorylation levels of AKT, ERK1/2, and NF-κB, and down-regulated the protein expression of COX-2. Conclusions: WJD showed beneficial effects in a CCBS-PD rat model. Synthesized assessments indicate a potential link to the actions of serum-exposed constituents, alterations in amino acid metabolism, and modulation of inflammation-related signaling pathways. This research offers initial indications suggesting the multi-component and multi-target pharmacological actions of WJD, although the underlying mechanisms remain to be validated through targeted metabolomics and functional studies. 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

Solidago canadensis is one of the most destructive invasive plants in China, and current physical and chemical control methods are often costly, inefficient, and ecologically risky, highlighting the urgent demand for green and efficient ecological alternatives. The native vine Humulus scandens exhibits strong allelopathic potential. In this study, allelochemicals from its leaves and stems were extracted using petroleum ether, ethyl acetate, n-butanol, and n-hexane. Their allelopathic effects on S. canadensis were systematically evaluated through seed germination, seedling growth, and rhizome propagation assays, combined with widely targeted metabolomics. Leaf extracts showed markedly stronger allelopathic inhibition than stem extracts. Among all fractions, the ethyl acetate extract exerted the most potent suppression on seed germination, significantly reducing germination rate and root elongation in a concentration-dependent manner. At 100 g·L⁻¹, leaf extracts—especially the ethyl acetate phase—significantly decreased belowground fresh weight, rhizome number, and new seedling emergence. The ethyl acetate extract also significantly elevated root antioxidant enzyme activities at 25–100 g·L⁻¹, indicating induced oxidative stress. UPLC-MS/MS-based metabolomics identified 186 differential metabolites among extracts. Ten flavonoids were significantly upregulated in the ethyl acetate extract and were predominantly enriched in the kaempferol aglycone biosynthesis I pathway (MetMap 113) and the flavonoid biosynthesis pathway (ko00941), suggesting that these compounds may play a key role in the observed allelopathic inhibition. Collectively, the ethyl acetate extract of H. scandens leaves effectively suppresses S. canadensis growth by inhibiting seed germination and rhizome tillering and by inducing oxidative stress, probably with the 10 candidate flavonoid metabolites, highlighting its strong potential as a biological control agent against this invasive weed. Full article