基于网络药理学探讨黄芪甲苷治疗非酒精性脂肪性肝病的作用机制  

Mechanism of astragaloside-Ⅳin the treatment of nonalcoholic fatty liver disease based on network pharmacology

作　　者：刘应莉[1] 刘璇 王艳荣[1] 张其良 张秋瓒[1] LIU Yingli;LIU Xuan;WANG Yanrong;ZHANG Qiliang;ZHANG Qiuzan(Department of Gastroenterology,Tianjin Fourth Central Hospital/The Fourth Central Hospital Affiliated to Nankai University,Tianjin 300140,China;Department of Pharmacology,Tianjin Fourth Central Hospital/The Fourth Central Hospital Affiliated to Nankai University,Tianjin 300140,China)

机构地区：[1]天津市第四中心医院/南开大学附属第四中心医院消化内科,天津300140 [2]天津市第四中心医院/南开大学附属第四中心医院药理科,天津300140

出　　处：《现代医药卫生》2023年第14期2372-2378,共7页Journal of Modern Medicine & Health

基　　金：天津市中医药管理局中医、中西医结合科研基金项目(2019127);天津市第四中心医院院级优秀人才培养计划项目(tjdszxyy20210016)。

摘　　要：目的基于网络药理学方法探讨黄芪甲苷(AS-Ⅳ)治疗非酒精性脂肪性肝病(NAFLD)的潜在作用机制。方法通过PharmMapper、Swiss-Target-Prediction、HERBs、TCMSP、ETCM数据库建库以来至2022年6月预测AS-Ⅳ的潜在作用靶标,搜索GeneCards、OMIM数据库中NAFLD的疾病靶标,利用Cytoscape软件获得AS-Ⅳ治疗NAFLD潜在作用靶标,利用String绘制靶标蛋白质互作网络图,并进行基因本体功能注释分析及京都基因与基因组百科全书信号传导通路的富集分析。结果AS-Ⅳ可能作用于蛋白激酶B丝氨酸/苏氨酸激酶1、血管内皮生长因子A、表皮生长因子受体、一氧化氮合酶3、雌激素受体1、半胱天冬酶3、哺乳动物雷帕霉素蛋白、过氧化物酶体增殖物激活受体γ等32个靶点,进一步调节环磷酸鸟苷-蛋白激酶G、哺乳动物雷帕霉素蛋白、胰岛素抵抗、腺苷酸活化蛋白激酶、丝裂原活化蛋白激酶、磷酸肌醇-3激酶-蛋白激酶B等多个信号通路,发挥负性细胞死亡调节、细胞信号传导、正向分子功能调节、氧化应激反应抑制等多种生物学功能,抑制NAFLD发病过程中的炎性反应、氧化应激和胰岛素抵抗等机制。结论AS-Ⅳ可通过多靶点、多通路对NAFLD发挥作用,可能是NAFLD潜在的治疗药物。Objective To investigate the potential mechanism of astragalosideⅣ(AS-Ⅳ)in the treatment of nonalcoholic fatty liver disease(NAFLD)based on network pharmacology.Methods The potential targets of AS-Ⅳwere predicted by PharmMapper,Swiss-Target-Prediction,HERBs,TCMSP,ETCM databases until June 2022,and the disease targets of NAFLD were searched in Genecards and OMIM databases.The potential targets of AS-IV in the treatment of NAFLD were obtained by Cytoscape software,and PPI maps of targets were drawn by String.Furthermore,the function annotation analysis of gene ontology and the enrichment analysis of signal transduction pathway in Kyoto encyclopedia of genes and genomics were carried out.Results AS-Ⅳmay work on protein kinase B serine/threonine kinase 1,vascular endothelial growth factor A,epidermal growth factor receptor,nitric oxide synthase 3,estrogen receptor 1,caspase 3,mammalian target of rapamycin,peroxisome proliferator-activated receptor-γand other 32 targets,and futher regulated cyclic guanosine phosphate-protein kinase G,mammalian rapamycin protein,insulin resistance,adenylate-activated protein kinase,mitogen-activated protein kinase,phosphoinositide-3 kinase-protein kinase B and other signaling pathways,exerted negative cell death regulation,cell signal transduction,positive molecular function regulation,and inhibited oxidative stress response and other biological functions.It could inhibit the inflammatory reaction,oxidative stress and insulin resistance in the pathogenesis of NAFLD.Conclusion AS-Ⅳcan play a role in the treatment of NAFLD through multiple targets and pathways,which may be a potential therapeutic drug for NAFLD.

关 键 词：黄芪甲苷 非酒精性脂肪性肝病 网络药理学 作用机制 多靶点治疗 

分 类 号：R575[医药卫生—消化系统] R282.71[医药卫生—内科学]