中草药2026，Vol.57Issue(18)：7124-7137,14.DOI:10.7501/j.issn.0253-2670.2026.18.005
整合网络药理学探讨洋川芎内酯A诱导肝星状细胞衰老缓解肝纤维化作用及机制
Effect and mechanism of senkyunolide A against liver fibrosis via inducing hepatic stellate cell senescence using integrated network pharmacology
摘要
Abstract
Objective To explore the mechanisms by which by which senkyunolide A(SenA)ameliorated liver fibrosis via inducing hepatic stellate cells(HSCs)senescence in vitro and in vivo.Methods SenA targets and liver fibrosis related targets were obtained using the SwissTargetPrediction database and GeneCards database.The intersection targets were used for gene ontology(GO)function and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.Metascape was used to analyze protein-protein interaction(PPI)network,core targets were screened and confirmed,functional enrichment analysis on core targets was performed,and molecular docking with SenA was performed.A mouse model of liver fibrosis was established using common bile duct ligation.Human hepatic stellate LX-2 cells and rat hepatic stellate HSC-T6 cells were induced using transforming growth factor-β1(TGF-β1)and platelet-derived growth factor-BB(PDGF-BB),respectively.After SenA intervention,senescence indicators were characterized by senescence-associated-β-galactosidase(SA-β-Gal)staining,EdU staining,qRT-PCR,etc.Results The results of network pharmacology revealed that SenA and liver fibrosis shared 39 common targets,the common target genes were enriched in cellular senescence pathways.A total of 19 genes obtained based on PPI network maybe the core targets of SenA on regulation of liver fibrosis progression,and it was found that core targets related to cellular aging are highly expressed in HSCs.Combining molecular docking experiments,it was found that SenA had the strongest binding ability to Aurora kinase A(AURKA),suggesting that AURKA may be a key molecular target for SenA in HSCs.The results of in vivo and in vitro experiments showed that SenA significantly induced HSCs senescence(P＜0.05,0.01,0.001),significantly downregulated the expressions of proliferation related genes Cyclin D1(CCND1)and cyclin dependent kinase 2(CDK2)(P＜0.05,0.01),and upregulated the expressions of senescence related genes p21,tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)(P＜0.05,0.01),thereby significantly inhibiting HSC activation and collagen deposition(P＜0.05,0.01,0.001).Conclusion SenAinduces HSC senescence to inhibit HSC activation,thereby improving liver fibrosis.关键词
洋川芎内酯A/衰老/肝纤维化/肝星状细胞/衰老相关分泌表型Key words
senkyunolide A/senescence/liver fibrosis/hepatic stellate cells/senescence associated secretory phenotypes分类
医药卫生引用本文复制引用
董明行,李晓骄阳,霍子璇,李佳楠,王馨,杨紫涵,唐恺悦,曲姣蓉..整合网络药理学探讨洋川芎内酯A诱导肝星状细胞衰老缓解肝纤维化作用及机制[J].中草药,2026,57(18):7124-7137,14.基金项目
国家自然科学基金青年项目(82404984) （82404984）
中央高校基本科研业务费专项资金(2024-JYB-JBZD-055) （2024-JYB-JBZD-055）
