基于网络药理学探讨葛根治疗肝损伤的作用机制

Network pharmacology-based prediction of Pueraria lobata for treating liver injury

目的:探究葛根治疗肝损伤的有效成分、靶标和作用通路,为葛根用于肝损伤的治疗提供理论依据。方法:基于中医药整合药理学网络计算平台(TCMIP)、中药综合资源数据库(TCMID)、中药系统药理数据库和分析平台(TCMSP)、人类基因数据库(GeneCards)等公共数据库和KEGG通路分析等网络药理学基本方法预测葛根治疗肝损伤的作用机制。结果:葛根主要活性成分靶点与肝损伤靶点具有交集,功能分析、富集分析和分子对接发现,刺芒柄花素、β-谷甾醇与雌激素受体1(ESR1),香豆雌酚、3′-甲氧基大豆黄素与PPARG与之间对接具有良好的亲和力,其中刺芒柄花素与ESR1之间作用力最强(-8.04 kcal/mol)。推断葛根治疗肝损伤的机制与ESR1和PPARG介导的路径相关。结论:葛根治疗肝损伤可能通过ESR信号通路、PPAR-γ激活和调节靶基因转录等发挥调节肝细胞的生长、分化和生理功能,减轻氧化应激性肝损伤和肝细胞凋亡的作用。

OBJECTIVE:To investigate the active ingredients,targets,action pathways and mechanisms of actions of Pueraria lobata for treating liver injury.METHODS:According to the public databases such as TCMID,TCMIP,TCMSP,GeneCards,and basic network pharmacological methods such as KEGG pathway analysis,potential pathways of pueraria for treating liver injury were predicted.RESULTS:The main active components of puerariae showed intersection with liver injury.Functional analysis,enrichment analysis and molecular docking showed that formononetin,β-sitosterol and ESR1,coumestrol,3′-methoxydaidzein and PPARG have good affinity for docking.The interaction between formononetin and ESR1 was the strongest(-8.04 kcal/mol).It was concluded that the mechanism of Pueraria lobata treating liver injury was related to ESR1 and PPARg-mediated pathway.CONCLUSION:The use of Pueraria lobata for treatment of liver injury may be mainly due to regulating the growth,differentiation and physiological functions of hepatocytes through estrogen receptor signaling pathway and PPAR-γactivation and regulation of target gene transcription expression pathway,and alleviating the mechanism of oxidative stress induced liver injury and hepatocyte apoptosis.