基于网络药理学和分子对接探讨黄连治疗高脂血症的作用机制

To explore mechanism of Coptidis Rhizoma for treating hyperlipidemia based on network pharmacology and molecular docking

目的采用网络药理学方法和分子对接,研究黄连治疗高脂血症的作用机制。方法借助中药系统药理学分析平台(TCMSP)检索黄连主要活性成分,利用SwissTargetPrediction数据库和TargetNet数据库,获取黄连活性成分对应的作用靶点。通过GeneCards、OMIM和Drugbank数据库筛选高脂血症相关靶点。使用Venny2.1汇总化合物靶点和疾病靶点交集基因并绘制韦恩图。运用Cytoscape 3.8.2绘制“黄连-成分-靶点-高脂血症”的网络图。通过STRING构建黄连-高脂血症核心靶点的PPI网络。采用R软件与Bioconductor工具包进行关键靶基因GO与KEGG功能富集分析,通过文献分析黄连治疗高脂血症的作用机制。最终对黄连主要活性成分与核心靶点进行分子对接验证。结果获取黄连14个活性成分,关联138个作用靶点。黄连主要涉及脂质代谢过程的调节等生物过程,通过作用核心靶点AKT1、TNF、EGFR等并通过调节AGE-RAGE信号通路、TNF信号通路、AMPK信号通路、脂肪细胞中脂解的调节等信号通路来发挥降脂作用。分子对接结果证明黄连主要活性成分与核心靶点结合潜能较好。结论本研究证明黄连治疗高脂血症具有多成分-多靶点-多通路的作用特点,其所作用的多条信号通路均存在直接或间接关联性,为临床用药提供了新的参考价值。

Objective Using network pharmacological methods and molecular docking,the mechanism of action of Coptidis Rhizoma was investigated in the treatment of hyperlipidemia.Methods The main active components of Coptidis Rhizoma were retrieved with using TCMSP database.The corresponding action targets of active components of Coptidis Rhizoma were retrieved by using SwissTargetPrediction and TargetNet database.Hyperlipidemia related targets were screened by GeneCards,OMIM and Drugbank database.Venny 2.1 was used to summarize compound target and disease target intersection genes and draw Wayne diagram.The network diagram of"drug-component-target-disease"was constructed by Cytoscape 3.8.2.PPI network was constructed by STRING.Based on R software andBioconductor bioinformatics software package were used to analyze the functional enrichment of key target genes GO and KEGG,and the mechanism of Coptidis Rhizoma in the treatment of hyperlipidemia was analyzed through the literatures.Finally,the main active components ofCoptidis Rhizoma and its core targets were verified by molecular docking.Results 14 active components of Coptidis Rhizoma were screened,association related 138 action targets.It was shown that Coptidis Rhizoma mainly involved biological processes such as regulation of lipid metabolic processes.Coptidis Rhizoma played a lipid-lowering role by acting on the core targets AKT1,TNF and EGFR,and by regulating AGE-RAGE signaling pathway,TNF signaling pathway,AMPK signaling pathway and regulation of lipolysis in adipocytes.The results of molecular docking showed that the main active components of Coptidis Rhizoma had good binding potential with the core target.Conclusion This study proves that Coptidis Rhizoma has characteristics of multi-component,multi-target and multi-pathway in the treatment of hyperlipidemia,and its multiple signaling pathways are directly or indirectly related,to better serve the clinical sharing of new reference value.