Multi-target Mechanism Research Articles

IntroductionHypertensive nephropathy (HN) is a common complication of hypertension. Clinically, there is an urgent need for new HN treatment strategies. Sijunzitang (SJZT) is widely used in clinical practice, but its therapeutic effects and pharmacological mechanisms in the treatment of HN remain unclear.MethodsThe active components, key targets, and potential pharmacological mechanisms of SJZT in treating HN were investigated through mass spectrometry, network pharmacology, and molecular docking. Subsequently, we validated the therapeutic effects of SJZT and the potential mechanisms using an Angiotensin II (Ang II)-induced HN mouse model and primary renal fibroblasts in vitro.ResultsNetwork pharmacology identified 87 active components and 26 potential therapeutic targets of SJZT in treating HN, among which PPARγ, TNF, CRP, ACE, and HIF-1α were identified as key targets. Molecular docking demonstrated strong binding affinity between the core active components (Licoisoflavone B, Glabrone, and Frutinone A) and PPARγ. Animal experiments revealed that SJZT attenuated renal damage and extracellular matrix deposition in HN model mice. In vitro experiments revealed that SJZT suppressed Ang II-induced renal fibroblasts activation, as evidenced by reduced cell viability, α-SMA, and Collagen I expression. Mechanistically, SJZT alleviated hypertensive renal fibrosis through PPARγ upregulation in renal fibroblasts, subsequently inducing autophagy activation.ConclusionThis preclinical study establishes that SJZT ameliorates HN through a multi-component, multi-target, and multi-pathway mechanism. Key findings confirm that SJZT activates autophagy via PPARγ upregulation, which subsequently inhibits renal fibroblast activation and attenuates HN progression. These results provide a pharmacological foundation for the translational application of SJZT in HN treatment.

This study investigated the potential of the deep-sea-derived fungal metabolite, chlorinated azaphilone compound chaetomugilin O, in the treatment of thyroid cancer. Chaetomugilin O was extracted from the fungus Chaetomium globosum YP-106 and subjected to in vitro experiments. The results demonstrated that this compound significantly inhibited the proliferation of thyroid cancer CAL-62 cells in a dose-dependent manner, with an IC50 value of 13.57 µM. Further mechanistic studies revealed that chaetomugilin O exerts its antitumor effects by inducing reactive oxygen species (ROS) accumulation, G2/M phase cell cycle arrest, and apoptosis. Transcriptomic analysis indicated its regulatory role in the PI3K-Akt signaling pathway, suggesting a multi-target synergistic antitumor mechanism. Molecular docking confirmed that chaetomugilin O binds to the Akt protein, forming a hydrogen bond with Lys158, implying its potential to directly inhibit Akt activity and interfere with PI3K-Akt pathway function. This study provides experimental evidence for the development of novel, low-toxicity, highly effective therapeutic agents for thyroid cancer.

Isoliquiritigenin micellar microneedle for pH monitoring and diabetic wound healing

As a global public health challenge, ocular diseases are driven by interconnected mechanisms, including oxidative stress, vascular abnormalities, and neurodegeneration. This review analyzes the multitarget mechanisms of berry-derived bioactive components (anthocyanins, proanthocyanidins, vitamin C, lutein, zeaxanthin, quercetin, and resveratrol) in regulating ocular homeostasis. Beyond antioxidant and anti-inflammatory effects, these compounds delay the progression of age-related macular degeneration, diabetic retinopathy, and glaucoma through mechanisms such as improving microcirculation, protecting photoreceptors, modulating angiogenesis, and inhibiting advanced glycation end-product deposition. Their protective effects involve the synergistic regulation of PI3K/AKT, Nrf2/HO-1, and VEGF pathways, supporting berry-based nutritional interventions for ocular health. Bioavailability and metabolism of these compounds are also discussed, highlighting their translational potential for the prevention and adjunctive therapy of ocular diseases.

Type 2 diabetes mellitus (T2DM), characterized by insulin resistance (IR) and hepatic ectopic lipid deposition (ELD), poses a complex metabolic challenge. This study aimed to elucidate the mechanisms of Yiqi Huazhuo Decoction (YD) through an inte-grated approach combining network pharmacology and metabolomics. T2DM is marked by impaired insulin signaling and disrupted hepatic lipid metabolism, resulting in a vicious cycle that accelerates disease progression. While Traditional Chinese Medicine (TCM), such as YD, demonstrates potential in modulating these dysfunctions, its underlying molecular mecha-nisms remain to be fully clarified. A diabetic fat rat model was used to evaluate the efficacy of YD. UPLC-MS characterized the main metabolites found in YD. After an 8-week intervention, physiological indices and hepatic pathology were assessed. Network pharmacology identified bioactive metabolites and targets, which were validated by molecular docking. Untargeted metabolomics was employed to analyze hepatic metabolic changes. YD improved glucose/lipid metabolism, insulin sensitivity, and hepatic function. Net-work pharmacology revealed that YD acts via the EGFR and PI3K-Akt/IL-17 pathways. Mo-lecular docking confirmed luteolin-EGFR binding. Metabolomics identified 20 altered metab-olites in the biosynthesis of unsaturated fatty acids. Multi-omics analysis revealed that YD regulated EGFR and hepatic metabolic networks. The multi-metabolite, multi-target mechanism of YD distinguishes it apart from single-target drugs, such as metformin. The binding of luteolin to EGFR may potentially re-activate the PI3K-Akt signaling pathway, thereby enhancing insulin sensitivity. Regulation of metabolic pathways, including the biosynthesis of unsaturated fatty acids, contributes to the reduction of hepatic lipid deposition. These findings underscore the capacity of YD to disrupt the IR-ELD cycle in T2DM. YD ameliorates T2DM-IR and hepatic ELD by modulating EGFR signaling and metabolic pathways, providing multi-omics evidence for its clinical application.

Nasopharyngeal carcinoma (NPC) is highly sensitive to radiotherapy, which, however, may trigger complications such as radiation-induced sinusitis (RIS) to impair patients' quality of life. Modified Sijunzi decoction (SJZD), a traditional Chinese medicine (TCM) formulation, has been revealed to exert therapeutic potential in RIS prevention and management. However, at this stage, we know little about its specific composition and molecular mechanism, which was a focus of our current study. This cross-sectional study was conducted on 86 NPC patients treated at our institution between August 2019 and August 2022. This study further assessed the association between TCM use and RIS incidence by using univariate analysis and multivariate logistic regression. Association rule mining and cluster analysis were employed to identify modified SJZD as the core prescription. Network pharmacology analysis was further applied to elucidate its mechanism of action. Univariate analysis demonstrated that TCM exposure was associated with reduced RIS prevalence (55.81%) (P = 0.002), and binary logistic regression analysis confirmed TCM use as an independent protective factor against RIS development (P = 0.001, OR = 0.156, 95% CI: 0.050-0.487). Furthermore, cluster analysis and association rule mining indicated that modified SJZD emerged as the core therapeutic prescription. Network pharmacology analysis identified 67 potential molecular targets of modified SJZD in RIS treatment. In addition, KEGG pathway enrichment revealed that modified SJZD exerted its therapeutic effects through multi-target mechanisms, particularly involving pathways in cancer, microRNAs in cancer, the JAK-STAT signaling pathway, and the NF-κB signaling pathway. There is a potential inverse association between TCM use and RIS incidence. Modified SJZD is identified as the core therapeutic formula, which appears to exert its protective effects through multiple bioactive components, diverse molecular targets, and multiple pathways.

ObjectiveTo investigate the pharmacodynamic material basis, multi-target mechanisms of Chelidonii Herba in treating chronic obstructive pulmonary disease (COPD), and its hepatotoxicity pathways using network pharmacology, network toxicology, and molecular docking.MethodsActive components and targets of Chelidonii Herba were screened via Traditional Chinese Medicine Systems Pharmacology (TCMSP), SwissTargetPrediction (STP), and PharmMapper databases. COPD and hepatotoxicity targets were obtained from GeneCards and OMIM. Venn diagrams identified shared targets. Protein-protein interaction (PPI) networks were constructed using STRING, with core targets filtered via CytoNCA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed in Metascape. Molecular docking was validated by AutoDock Vina, and immune infiltration was analyzed using the GSE55962 dataset.ResultsTwenty active components and 108 potential targets of Chelidonii Herba were identified. Eighty shared targets intersected with COPD, and 96 with hepatotoxicity. Seven core targets for COPD treatment (CASP3, PPARG, PTGS2, CDK2, ALB, HSP90AA1, ESR1) and hepatotoxicity (PPARG, ESR1, CASP3, PTGS2, ESR2, CALM3, ALB) were determined. KEGG enrichment revealed COPD mechanisms involving PI3K-Akt, VEGF, and cGMP-PKG pathways, while hepatotoxicity implicated VEGF, PI3K-Akt, and estrogen signaling. Core components (e.g., dihydrochelerythrine, oxysanguinarine) exhibited strong binding to targets (binding energy ≤ −5.0 kcal/mol, partial ≤ −7.0 kcal/mol). Immune infiltration analysis linked core targets to macrophages M2 and γδ T cells.ConclusionChelidonii Herba treats COPD primarily through alkaloids modulating shared targets (CASP3, PPARG, PTGS2) via PI3K-Akt pathways, while concurrently inducing hepatotoxicity through VEGF and estrogen signaling. This dual efficacy-toxicity profile necessitates cautious clinical application and experimental validation to define safe therapeutic windows.

Dietary supplementation with selenium yeast mitigates diquat-induced oxidative damage in oviductal magnum of hens.

Integrating metagenomics, lipidomics and proteomics to explore the effect and mechanism of ginsenoside Rb1 on atherosclerosis co-depression disease.

Introduction: The ability of salt-processed Alismatis Rhizoma (SAR) (Alisma plantago-aquqtica L.) to nourish Yin and promote urination is stronger than that of Alismatis Rhizoma (AR). However, there are few studies focused on evaluating the quality of its medicinal materials. Objectives: This study aimed to identify potential quality markers (Q-markers) for SAR, thereby providing a more reliable basis for its quality control and clinical application. Methods: Q-markers were identified through fingerprinting and chemical pattern recognition analysis of 15 batches of SAR. The diuretic effects of these markers were then verified by network analysis and molecular docking. Results: HPLC fingerprints of 15 SAR batches were established, with similarity analysis showing values > 0.85 (0.852–0.990). Chemical pattern recognition identified six critical compounds contributing to SAR quality: alisol F, alisol C 23-acetate, alisol A, alisol A 24-acetate, alisol B 23-acetate, and an alisol O isomer (VIP > 1.0). Network analysis revealed 76 overlapping targets between these compounds and diuretic-related diseases, with core targets including non-receptor tyrosine kinase (SRC), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 1 (MAPK1), which were identified through protein–protein interaction (PPI) network analysis, with degrees of 27, 24, and 22, respectively. Key pathways involved were the EGFR tyrosine kinase inhibitor resistance pathway, calcium signaling pathway, tumor necrosis factor signaling pathway, etc. Molecular docking confirmed strong binding interactions between the Q-markers and the hub targets, particularly alisol B 23-acetate with MAPK1 (−60.10 kcal·mol−1) and alisol A 24-acetate with EGFR (−46.14 kcal·mol−1) and SRC (−48.86 kcal·mol−1). The diuretic effects of SAR are likely mediated through anti-inflammatory actions and regulation of water–sodium balance via multi-target and multi-pathway mechanisms. Conclusion: This study provides a robust foundation for quality control and clinical application of SAR, though further in vivo validation is warranted.

Cancer continues to be a major global health challenge, with existing treatments often causing severe side effects, drug resistance, and high costs. Plant-derived anticancer peptides (PDACPs) have emerged as a promising alternative due to their high specificity, multi-target mechanisms, and safety profile. This review summarizes the sources (e.g., legumes, cereals, and medicinal plants), mechanisms of action, and therapeutic potential of PDACPs, highlighting their role in apoptosis induction, cell cycle arrest, anti-angiogenesis, and metastasis inhibition. Mechanistic investigations reveal that PDACPs exert anticancer effects through multiple pathways, including the induction of apoptosis via mitochondrial membrane disruption and the upregulation of pro-apoptotic factors, the inhibition of cell proliferation by arresting cell-cycle progression, the suppression of angiogenesis through the downregulation of vascular endothelial growth factor signaling, and the disruption of tumor-associated membrane integrity. Preclinical studies suggest that, compared to conventional chemotherapeutics, PDACPs may offer advantages such as enhanced tumor selectivity, reduced off-target toxicity, and diminished likelihood of resistance development. We also discuss current challenges in peptide stability, delivery, and large-scale production, and propose strategies, such as nanoparticle encapsulation, to enhance clinical viability. This comprehensive synthesis underscores the potential of PDACPs as next-generation anticancer therapeutics and paves the way for translational development.

BackgroundKaixin San Jiawei Granule (KSG) is a traditional Chinese medicine formulation derived from classical prescriptions. Although it has shown promise in treating Alzheimer’s disease (AD), its precise mechanisms of action remain unclear. This study aimed to systematically investigate the molecular mechanisms underlying KSG’s therapeutic effects on AD through an integrative approach combining network pharmacology with experimental validation.MethodsAn in vivo AD model was established in male KM mice via intraperitoneal injection of scopolamine. Cognitive function was assessed using the Morris water maze, and hippocampal levels of acetylcholine (ACh), acetylcholinesterase (AChE), glutathione peroxidase (GSH-Px), and reactive oxygen species (ROS) were measured using ELISA. In vitro, PC12 cells were exposed to Aβ25-35 to induce apoptosis. Immunofluorescence staining, Western blotting, and qPCR were used to assess the expression of amyloid-beta (Aβ), apoptosis-related protein caspase-3, and inflammatory cytokines (TNF-α, IL-1β). Active components of KSG and their potential targets and pathways were identified using mass spectrometry and network pharmacology, while partial validation was performed using molecular docking and Western blotting.ResultsIn vivo, KSG significantly alleviated scopolamine-induced cognitive deficits in mice. Treatment increased hippocampal levels of ACh and GSH-Px while reducing AChE and ROS. In vitro, KSG mitigated Aβ25-35-induced cytotoxicity in PC12 cells, decreased Aβ accumulation, and downregulated the expression of TNF-α and IL-1β. However, KSG had no significant effect on telomerase activity, telomere length, or the expression of the telomere-associated protein POT1. Mass spectrometry and network pharmacology analyses identified genistein, quercetin, and apigenin as key active compounds with TP53, AKT1, PTGS2, and CNR2 identified as core targets. Molecular docking validation confirmed the favorable binding activity between them. The calcium signaling, PI3K-Akt, and MAPK pathways emerged as the primary enriched pathways.ConclusionKSG improves cognitive function and attenuates Aβ-induced neuronal damage in AD through multi-component, multi-target synergistic mechanisms. These effects appear to be mediated by modulation of the cholinergic system, inhibition of oxidative stress and inflammation, and suppression of neuronal apoptosis. These findings provide a theoretical basis and experimental support for developing novel AD therapies based on traditional Chinese medicine.

BackgroundConstipation is a common gastrointestinal disorder with significant public health implications, particularly among aging populations. Current treatment options often exhibit limited efficacy and may have potential side effects, underscoring the necessity for safer and more effective alternatives. Postbiotics, which are bioactive metabolites derived from probiotics, have emerged as promising therapeutic agents due to their stability, safety, and multifunctional properties. Postbiotic of hawthorn-probiotic has demonstrated potential in alleviating constipation; however, its mechanisms-particularly regarding the regulation of intestinal epithelial cell apoptosis and the gut microenvironment-remain to be fully elucidated.MethodsThis study employed murine models of loperamide-induced constipation and in vitro assays using NCM460 intestinal epithelial cells. Conditioned medium mimicking the gut microenvironment was prepared from colonic contents of different groups of mice. Cell viability and apoptosis levels were assessed using flow cytometry and fluorescence microscopy, while molecular pathways were analyzed through RT-qPCR and Western blot techniques. Network pharmacology was employed to integrate transcriptomic data for identifying core targets and pathways.ResultsPostbiotic of hawthorn-probiotic significantly downregulated apoptotic (CASP3, CASP9) and pyroptotic (NLRP3, GSDMD, CASP1) pathway components while restoring the balance of pro- and anti-apoptotic proteins (Bax/Bcl-2). Additionally, this postbiotic selectively modulated immune responses by reducing Th2/Th17-type cytokines (IL-2, IL-17A), without affecting Th1-type responses. Network analysis revealed that the action of hawthorn-probiotic postbiotics involves multiple targets including CASP8/CASP3-mediated cell death as well as STAT3/NF-κB signaling pathways.ConclusionsPostbiotic of hawthorn-probiotic demonstrates efficacy in alleviating constipation through the multi-pathway inhibition of apoptosis and pyroptosis, alongside the remodeling of the immune microenvironment. Its multi-target mechanism and favorable safety profile position it as a promising therapeutic candidate. These findings lay a solid foundation for the development of interventions based on hawthorn-probiotic postbiotics for constipation and related gastrointestinal disorders.

Angiogenesis, the formation of new blood vessels from pre-existing vasculature, is essential for physiological processes such as development and wound healing, but its dysregulation contributes to a range of pathological conditions including cancer, diabetic retinopathy, and chronic inflammation. In recent years, marine-derived compounds have emerged as promising multitarget agents with anti-angiogenic potential. Posidonia oceanica, a Mediterranean seagrass traditionally used in folk medicine, is increasingly recognized for its pharmacological properties, including antioxidant, anti-inflammatory, and anti-invasive activities. This study investigated the effects of a hydroethanolic extract from P. oceanica leaves (POE) on human Endothelial Colony-Forming Cells (ECFCs), a subpopulation of endothelial progenitor cells with high proliferative and vessel-forming capacity, and a relevant model for studying pathological angiogenesis. ECFCs were treated with POE (4–8 µg/mL), and cell viability, morphology, migration, invasion, tube formation, oxidative stress, and activation markers were evaluated. POE did not alter ECFC morphology or viability, as confirmed by Trypan Blue and MTT assays. However, functional assays revealed that POE significantly impaired ECFC migration, invasion, and in vitro angiogenesis in a dose-dependent manner. Under VEGF (Vascular endothelial growth factor) stimulation, POE reduced intracellular ROS accumulation and downregulated key redox-regulating genes (hTRX1, hTRX2, PRDX2, AKR1C1, AKR1B10). Western blot analysis showed that POE inhibited VEGF-induced phosphorylation of KDR, mTOR and p-ERK, while p-AKT remained elevated, indicating selective disruption of VEGF downstream signaling. Furthermore, POE reduced the expression of pro-inflammatory and pro-coagulant markers (VCAM-1, ICAM-1, TF) and partially reversed TNF-α–induced endothelial activation. These findings suggest that POE exerts anti-angiogenic effects through a multitargeted mechanism, supporting its potential as a natural therapeutic agent for diseases characterized by aberrant angiogenesis.

Light-triggered carbon monoxide-induced activation of enhanced ferritinophagy-mediated ferroptosis for bone metastases therapy

Untangling the metabolome of resistant (VBN4) and susceptible (CO5) blackgram cultivar bacterized with Bacillus pumilus imparts resistance response against yellow mosaic disease.

Background: Diabetes and its associated complications encompass a range of comorbidities, including issues like impaired wound healing and chronic ulceration. It is very important to find an effective and economical way to manage diabetes and its complications. This review seeks to outline the mechanisms of action and potential drug targets of specific medicinal plants and derived compounds in healing diabetic wounds. Additionally, it aims to offer scientific evidence and research insights for their clinical application. Methods: A literature search was conducted using Google Scholar, PubMed, and Scopus for articles on diabetic wound healing published between 2001 and December 2024. Using relevant keywords, 3122 articles were identified. After screening and applying exclusion criteria, 63 studies were selected and categorized into medicinal plants, plant-derived molecules, and clinical studies to explore potential therapeutic targets. Results: Chronic diabetic wounds (DW) exhibit impaired healing across all wound repair phases, i.e., hemostasis, inflammation, proliferation, and remodelling. During hemostasis, defective coagulation and impaired platelet aggregation delay initial wound closure. The inflammatory phase is characterized by persistent inflammation, driven by elevated pro-inflammatory cytokines (e.g., TNF-α, IL-6), reduced anti-inflammatory mediators, and dysregulated NF-κB, MAPK, and PI3K/Akt signalling pathways, which exacerbate tissue damage. In the proliferative phase, diminished levels of growth factors (e.g., VEGF, PDGF) and disrupted signalling cascades impair angiogenesis, fibroblast proliferation, and extracellular matrix (ECM) synthesis, hindering tissue regeneration. The remodelling phase is compromised by chronic inflammation and an imbalance in matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) activity, resulting in defective collagen reorganization, reduced tensile strength, and poor wound maturation. Herbal medicines demonstrate potential in ameliorating these impairments by modulating dysregulated pathways, exerting anti-inflammatory, antioxidant, and proangiogenic effects, and promoting balanced wound repair across all phases. Nevertheless, rigorous scientific validation and standardized documentation of traditional medicinal practices are essential to confirm their therapeutic efficacy and safety in DW management. Conclusion: Diabetic wound management remains a major clinical challenge due to the limited efficacy and side effects of standard therapies. Medicinal plants and their bioactive compounds show promising healing potential through multi-targeted mechanisms. This review highlights a key research gap in the mechanistic understanding and clinical validation of traditional remedies, offering novel insights into targeting pathways like NF-κB, MAPK, and PI3K/Akt for improved diabetic wound care.

Purpose: This study aims to discuss the application value of the synergistic herb pairing concept of traditional Chinese medicine in treating Parkinson's disease and analyses its differences from and potential advantages over conventional Western therapies. From the perspective of synergistic herb pairings, this study takes three classic herb pairings, including the Tianma-and-Gouteng (Gastrodia-and-Uncaria) pairing, the Shudi-and-Yurou (Rehmannia-and-Cornus) pairing, as well as the Shaoyao-and-Gancao (Paeonia-Glycyrrhiza) pairing, as examples to examine and summarize the pairing rules, chemical pharmacology, and clinical efficacy. Results: Through different formula combinations, it is found that mutually reinforcing herb pairings can enhance clinical efficacy. Meanwhile, new active compounds formed during the decoction process, such as 4-Hydroxybenzyl alcohol extracted from Gastrodia elata and Rehmannia glutinosa polysaccharide produced during the processing of prepared Rehmannia root, exhibit stronger anti-neuronal apoptosis and neuroprotective effects. Conclusion: The concept of synergistic herb pairings in traditional Chinese medicine exerts therapeutic effects through multi-target mechanisms, showing unique advantages in the treatment of Parkinson's disease. In particular, it demonstrates clinical value in slowing disease progression and alleviating non-motor symptoms such as sleep disturbances and constipation. By integrating modern extraction technologies with optimized herb pairings, it can further enhance clinical efficacy and improve patients' quality of life.

Hyperuricemia is an increasingly serious metabolic disease. However, xanthine oxidase inhibitors (XOIs) can fundamentally solve the problem of uric acid overproduction. In this paper, through virtual screening and network pharmacology, 73 potential compounds are discovered from six Chinese herbal medicines containing phenylpropanoids. These compounds treat hyperuricemia through crucial targets XDH, IL6, TLR4, HIF1A, HSP90AA1 and MMP2 synergistic effect. Further assay activities of inhibitory xanthine oxidase and antioxidant discover that taxifolin, morin and ellagic acid are deserved further study as the most promising anti-hyperuricemia multi-target XOIs candidates. Therefore, this study provides certain theoretical foundation for exploring effective treatment of hyperuricemia.

Alternaria alternata is a globally distributed plant pathogen infecting >400 plant species. Trans-2-decenal is a notable plant-derived secondary metabolite with strong volatility and antifungal properties, although its specific activity and mode-of-action against A. alternata remain unclear. Toxicity assays showed that trans-2-decenal inhibited A. alternata with a median inhibitory concentration (IC50) of 12.23 mg L-1. Treated with trans-2-decenal resulted in hyphal abnormalities, reduced spore production and suppressed spore germination. Mechanistically, it disrupted fungal cell membrane integrity, as confirmed by propidium iodide staining and increased leakage of DNA and soluble proteins in conductivity assays. Further investigations revealed that trans-2-decenal disrupted redox homeostasis by inducing reactive oxygen species (ROS) accumulation. DCFH-DA fluorescence staining showed elevated ROS levels, whereas antioxidant enzyme assays revealed dose-dependent changes, including decreased superoxide anion (O2.-) and catalase (CAT) activity, and significantly increased hydrogen peroxide (H2O2), superoxide dismutase (SOD) and malondialdehyde (MDA) levels, collectively indicating oxidative stress and damage. Transcriptome analysis identified 2319 differentially expressed genes (DEGs), with gene ontology (GO) enrichment highlighting inhibition of pathways associated with oxidative stress response, transmembrane transport and ribosome biogenesis. Molecular docking further suggested interactions between trans-2-decenal and key antioxidant enzyme and membrane transporter of A. alternata. In vivo assays showed that 32 mg L-1 trans-2-decenal fumigation achieved protective and curative efficacies of 97.14% and 96.54%, respectively, against yam leaf spot disease. Trans-2-decenal inhibited A. alternata through a multitarget synergistic mechanism, providing theoretical support for its development as a plant-derived biofumigant and a promising tool for the green management of A. alternata-induced diseases. © 2025 Society of Chemical Industry.