基于网络药理学和分子对接探讨藏药“吉尼德协”治疗Ⅱ型糖尿病的作用机制  

Study on the mechanism of Tibetan medicine Ji Ni De Xie in the treatment of type Ⅱ diabetes mellitus based on netw ork pharmacology and molecular docking

作　　者：彭芳[1] 彭家艳 张琨[1] 罗玉婷 赵紫薇 范刚[1] PENG Fang;PENG Jia-yan;ZHANG Kum;LUO Yu-ting;ZHAO Zi-wei;FAN Gang(Chengdu University of Traditional Chinese Medicine,Chengdu,611137,Sichuan)

机构地区：[1]成都中医药大学,四川成都611137

出　　处：《中药与临床》2022年第6期51-56,共6页Pharmacy and Clinics of Chinese Materia Medica

基　　金：四川省科学技术厅重点研发项目(2022YFSO434);基于名老藏医验方的四川南派藏医药防治Ⅱ型糖尿病候选药物研究。

摘　　要：目的:运用网络药理学及分子对接探究藏药“吉尼德协”治疗Ⅱ型糖尿病(T2DM)的作用机制。方法:将吉尼德协的化学成分通过Swiss数据库筛选获得活性成分及靶点;检索Gencards、DrugBank、DisGeNET和OMIM数据库获取T2DM相关靶点;运用STRING在线数据分析和Cytoscape 3.8.2软件构建吉尼德协药材-活性成分-关键靶点复方调控网络图;利用Metascape数据库对交集靶点进行GO功能分析和KEGG富集分析;并利用Maestro 11.9软件进行分子对接。结果:检索获得活性成分159个及成分靶点749个,T2DM靶点2017个。GO功能分析显示吉尼德协治疗T2DM与磷酸转移酶活性、蛋白激酶结合和氧化还原酶活性有关,有膜筏、受体复合体及细胞核周质区域的参与。KEGG通路富集主要涉及AGE-RAGE通路和胰岛素信号通路。分子对接结果显示吉尼德协中的活性化合物与关键靶点结合构象稳定。结论:吉尼德协可能通过其含有的药根碱、小檗碱、姜黄素、蟾蜍特尼定、槲皮素、山奈酚等成分与AKT1、PIK3CA、MAPK1等靶蛋白结合,作用于AGE-RAGE、胰岛素信号等通路,从而调节糖脂代谢、氧化应激和炎症反应而发挥改善T2DM作用。Objective:To explore the mechanism of Tibetan medicine Ji Ni De Xie(JNDX)in the treatment of type Ⅱ diabetes mellitus(T2DM)based on network pharmacology and molecular docking.Method:The chemical components of JNDX were screened through the Swiss database to obtain the active components and targets.T2DM-related targets were obtained by searching the databases of Gencards,DrugBank,DisGeNET and OMIM.STRING online data analysis and Cytoscape 3.8.2 software were used to construct the compound regulatory network diagram of medicinal material-active component-critical target in JNDX.The Metascape database was used for GO functional analysis and KEGG enrichment analysis of intersection targets.Maestro 11.9 software was used for molecular docking.Result:159 active components,749 component targets and 2017 T2DM-related targets were retrieved.GO functional analysis showed that the treatment of T2DM by JNDX was related to phosphotransferase activity,protein kinase binding and oxidoreductase activity,with the involvement of membrane rafts,receptor complexes and cell periplasmic regions.KEGG pathway enrichment mainly involved AGE-RAGE pathway and insulin signaling pathway.Molecular docking results showed that the active compounds in the JNDX bound to critical targets in a stable conformation.Conclusion:JNDX may bind to AKT1,PIK3CA,MAPK1 and other target proteins through its components including jatrorrhizine,berberine,curcumin,bufotenidine,quercetin,kaempferol,etc.,acting on AGE-RAGE,insulin signaling and other pathways,thus improving T2DM by regulating glucose and lipid metabolism,oxidative stress and inflammatory response.

关 键 词：藏药 吉尼德协 Ⅱ型糖尿病 网络药理学 分子对接 作用机制 

分 类 号：R29[医药卫生—民族医学]