基于网络药理学及实验验证探讨绞股蓝提取物对抑郁症的干预作用OA

Objective To explore and verify the potential targets and mechanisms of Herba Gynostemmatis(HGM)intervention in depression.Methods Potential active components and targets of HGM against depression were screened from databases.A protein-protein interaction(PPI)network was constructed,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses to identify core targets and pathways.Molecular docking was performed using AutoDock to evaluate bind-ing affinities between key components and targets.The complex with the most favorable docking result was further assessed by molecular dynamics(MD)simulation using Gromacs software,including system equilibration(NVT and NPT)and production MD runs.In vitro validation was conducted using a corticosterone(CORT)-induced PC12 cell injury model.The effects of HGM on cell viability(CCK-8 assay),mitochondrial DNA(mtDNA)copy number(quantitative real-time PCR),and levels of inflammatory cytokines IL-6 and IL-1β(ELISA)were measured.Results Seven active components of HGM were identified,corresponding to 91 potential targets.Among these,85 targets overlapped with depression-related targets.The primary putative antidepressant components were rutoside and panaxa-diol,and the key potential targets included RXRA,ALB,and PTGS2.KEGG pathway analysis implicated several pathways,with the peroxisome proliferator-activated receptor(PPAR)signaling pathway and the inflammatory mediator regulation of transient receptor potential(TRP)channels being prominently enriched.Molecular docking indicated that rutoside exhibited the most favorable binding affinity with RXRA,suggesting RXRA as a crucial target.MD simulations further supported the stable binding of rutoside to RXRA.In CORT-injured PC12 cells,HGM treatment significantly reduced lactate dehydrogenase(LDH)release,increased mtDNA copy number,and decreased the level of IL-6.Conclusion HGM may alleviate depressive symptoms through bioactive components like ruto-side and panaxadiol.These components potentially act on targets such as RXRA,ALB,and PTGS2,thereby modulating the PPAR sig-naling pathway and TRP channel-related inflammatory mediator regulation.