[关键词]
[摘要]
目的 基于网络药理学探讨运脾汤治疗高脂血症的分子作用机制。方法 通过TCMSP、Pharm Mapper、GeneCards、DisGeNET等多个数据库检索,预测并收集运脾汤的有效化学成分和对应的靶蛋白以及高脂血症的相关疾病基因,筛选关键靶点,对关键靶点及相关有效化学成分做分子对接验证,利用DAVID数据库的富集分析功能,得到运脾汤的有效化学成分干预高脂血症的过程中涉及的相关功能和通路,并构建“中药材-有效化学成分-靶点-通路”综合网络。结果 运脾汤干预高脂血症的核心成分为木犀草素、槲皮素、山奈酚、柚皮素等;核心靶点PPARG、NOS3、EGFR、APOB和ESR1,分子对接验证,大部分靶点与化合物有结合活性较好;DAVID富集分析,运脾汤可能通过细胞内外刺激、脂多糖反应和调节凋亡等生物过程和HIF-1信号通路、AGE-RAGE信号通路、胰岛素信号通路、TNF信号通路等途径干预高脂血症。结论 本研究初步预测了运脾汤干预高脂血症的多成分、多靶点、多通路的作用机制,为进一步实验研究提供理论依据。
[Key word]
[Abstract]
Objective To explore the pharmacological mechanism of Yunpi Decoction in the treatment of hyperlipidemia by using the network pharmacological method.Methods Firstly, the effective chemical components and corresponding target proteins of Yunpi Decoction and related disease genes of hyperlipidemia were retrieved and predicted by consulting multiple databases, such as TCMSP, Pharm Mapper, GeneCard, and DisGeNET, etc. Secondly, The String platform was used for protein interaction analysis to construct key proteins in the PPI network mining network. the verification in molecular docking was performed by iGEMDOCK. Finally, The DAVID platform was adopted to analyze the “medicinals+components+targets+pathways” and the involved biological processes and pathways. Then, Cytoscape (3.6.0) software was used to construct the integrated network.Results The core components of Yunpi Decoction for intervening hyperlipidemia were luteolin, quercetin, kaempferol, and naringenin, etc. The main targets were PPARG, NOS3, APOB and ESR1; The verification in molecular docking verification also showed that most targets had a good binding activity with compounds. According to DAVID enrichment analysis, Yunpi Decoction might interfere with hyperlipidemia through biological processes such as intracellular and extracellular stimulation, lipopolysaccharide response, and HIF-1 signaling pathway, AGE-RAGE signaling pathway, and insulin signaling pathway.Conclusion This study preliminarily predicted the multi-component, multi-target, and multi-path action mechanism of Yunpi Decoction in the intervention of hyperlipidemia, and provided a theoretical basis for further experimental research.
[中图分类号]
R259
[基金项目]