基于网络药理学及分子对接研究健脾化浊调脂颗粒治疗非酒精性脂肪肝的分子作用机制

Molecular Mechanism of Jianpi Huazhuo Tiaozhi Granule against Non-Alcoholic Fatty Liver Based on Network Pharmacology and Molecular Docking

目的通过网络药理学及分子对接技术探讨健脾化浊调脂颗粒(国家专利号ZL 201510430075.8)治疗非酒精性脂肪肝的具体分子机制。方法通过中国知网、TCMSP、BATMAN-TCM 3个数据库对健脾化浊调脂颗粒主要成分及潜在作用靶点进行收集。从DisGeNET数据库中寻找与非酒精性脂肪肝相关的疾病基因与潜在靶点进行映射,得出健脾化浊调脂颗粒治疗非酒精性脂肪肝最终作用靶标。将最终靶标输入STRING数据库得出"蛋白-蛋白"相互作用关系,并用Cytoscape软件进行可视化。输入DAVID数据库进行KEGG PATHWAY富集,得出其可能作用的分子机制并构建"活性成分-靶标-作用通路"网络图。将"蛋白-蛋白"互作图中排名前5位靶标蛋白与君药进行分子对接,以验证其治疗作用。结果通过网络药理学预测后发现,健脾化浊调脂颗粒中有117个有效成分可用于治疗NAFLD,其中涉及113个靶基因及包括AMPK、PPAR、FOXO、胰岛素抵抗等18个信号通路。通过分子对接发现,5个靶标蛋白与君药结合性较好。结论从分子对接技术揭示了健脾化浊调脂颗粒有直接治疗非酒精性脂肪肝的作用,从网络药理学角度初步揭示了其治疗非酒精性脂肪的分子机制,为后续的研究提供了基础。

Objective Through the network pharmacology and molecular docking technology to explore the molecular mechanism of the treatment of non-alcoholic fatty liver by Jianpi Huazhuo Tiaozhi Granule. Method Firstly, the main components and potential targets of Jianpi Huazhuo Tiaozhi Granule were collected through three databases: CNKI, TCMSP and BATMAN-TCM. Secondly, genes related to non-alcoholic fatty liver disease were searched from the DisGeNET database. And then the gene and potential target were mapped to obtain the final target. Thirdly, entered into all target genes into the STRING database and obtained the protein-protein interaction relationship, visualized by Cytoscape software. At the same time, input all target genes into the DAVID database and obtained the molecular mechanism. Then we constructed the network of"compounds-targets-pathways". Finally, we used molecular docking to verify primal medicine and top five genes in the protein-protein interaction. Result Based on the network pharmacology prediction, it was found that 117 components in Jianpi Huazhuo Tiaozhi Granule could be used to treat non-alcoholic fatty liver, including 113 genes and 18 signaling pathways such as AMPK, PPAR, FOXO pathway and insulin resistance. Through molecular docking, top five proteins were found out to bind well to primal medicine. Conclusion This paper revealed Jianpi Huazhuo Tiaozhi Granule can directly treat non-alcoholic fatty liver by molecular docking technology. Through the network pharmacology, the molecular mechanism of Jianpi Huazhuo Tiaozhi Granule against NAFLD was revealed, which provides a basis for further research.