基于网络药理学探讨二陈汤治疗高脂血症的分子机制

Molecular mechanism of the Erchen decoction in the treatment of hyperlipidemia based on network pharmacology

目的:运用网络药理学及分子对接探索二陈汤治疗高脂血症的作用机制。方法:应用中药系统药理学数据库和分析平台(TCMSP)检索二陈汤活性成分及相关靶点,并使用Uniprot蛋白质数据库进行基因名转换;应用GeneCards、DRUGBANK、TTD、OMIM数据库检索高脂血症的靶点;通过Venny 2.1.0获取交集靶点,基于交集靶点进行蛋白质相互作用分析、基因本体论(GO)功能与京都基因与基因组百科全书(KEGG)信号通路富集分析;最后应用SYBYL软件进行核心靶点分子对接。结果:获取二陈汤靶点210个、高脂血症靶点1575个,两者匹配后获得交集靶点120个;蛋白质-蛋白质相互作用网络中前10个核心靶点依次为丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase 1,AKT1)、白细胞介素(Interleukin,IL)-6、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、IL-1B、血管内皮生长因子A(Vascular Endothelial Growth Factor A,VEGFA)、肿瘤抑制蛋白p53(Tumor Protein p53,TP53)、半胱天冬酶3(Caspase 3,CASP3)、过氧化物酶体增殖物激活受体γ(Peroxisome Proliferator Activated Receptor Gamma,PPARG)、前列腺素G/H合酶2(Prostaglandin-Endoperoxide Synthase 2,PTGS2)、缺氧诱导因子-1α(Hypoxia Inducible Factor-1 Subunit Alpha,HIF1A);富集分析条目共320个,KEGG富集到46条通路。分子对接发现其中β-谷甾醇与CASP3结合活性最强。结论:二陈汤可通过多靶点、多通路治疗高脂血症。

Objective:To explore the mechanism of the Erchen decoction(二陈汤)in treating hyperlipidemia by network pharmacology and molecular docking.Methods:The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)was used to retrieve the active ingredients and related targets of the Erchen decoction,and gene name conversion was performed by Uniprot protein database.The GeneCards,DRUGBANK,TTD and OMIM databases were used to retrieve the targets of hyperlipidaemia.The intersecting targets were obtained through Venny 2.1.0,and based on the intersecting targets protein interaction analysis,GO function and KEGG signalling pathway enrichment analysis were performed,and finally SYBYL software was used for core target molecular docking.Results:The top ten core targets obtained in the PPI network were AKT1,IL-6,TNF,IL-1B,VEGFA,TP53,CASP3,PPARG,PTGS2,HIF1A in order,with a total of 320 enrichment analysis entries and 46 signaling pathways of KEGG enrichment analysis.Molecular docking revealed thatβ-sitosterol had the strongest binding activity to CASP3.Conclusion:The Erchen decoction can treat hyperlipidaemia through multiple targets and pathways.