基于网络药理学及分子对接技术探讨辣木叶抗肥胖的作用机制

李婷婷; 管亚; 弘子姗; 解静; 田洋

doi:10.13386/j.issn1002-0306.2022090318

基于网络药理学及分子对接技术探讨辣木叶抗肥胖的作用机制

Study on the Anti-obesity Mechanism of Action of Moringa oleifera Lam. Leaves by Network-Based Pharmacology and Molecular Docking Techniques

摘要

摘要: 目的：本研究基于网络药理学和分子对接技术预测和验证辣木叶活性成分抗肥胖的分子靶点和途径，探索辣木叶活性成分的抗肥胖作用及潜在机制。方法：利用PubChem、DisGeNET数据库和SwissADME、Swiss Target Prediction在线预测平台获取辣木叶活性成分靶点和肥胖相关靶点；利用Venny 2.0.1平台对活性成分靶点和肥胖相关靶点取交集，筛选出关键靶点，并利用STRING 11.0数据库进行PPI网络的核心靶点分析；采用Cytoscape 3.8.2软件，构建“成分-靶点”相互作用网络，筛选出核心活性成分；基于David数据库进行GO功能富集和KEGG通路分析；最后，运用Auto Dock 4.2软件对通路富集靶点与核心成分进行分子对接。结果：筛选出辣木叶活性成分50个，共确定了126个辣木叶抗肥胖的核心靶点，其中主要活性成分为鼠李黄素、胆甾-5烯-3醇、杨梅素、木犀草素等。GO及KEGG分析结果显示，辣木叶活性成分通过RNA聚合酶Ⅱ启动子转录的正调控、信号传导、基因表达的正调控、蛋白质磷酸化及凋亡表达的负调控等生物过程，通过HIF-1、胰岛素抵抗、二型糖尿病、胰岛素信号通路等多条通路发挥抗肥胖作用。分子对接结果表明11个核心成分均与靶点结合，其中靶点PIK3R1与鼠李黄素呈现出最低的亲和力，为−9.2 kcal/mol，PIK3CA与胆甾-5烯-3醇为−9.1 kcal/mol，PIK3R1与杨梅素为−8.8 kcal/mol，AKT1与木犀草素为−8.7 kcal/mol。结论：本研究揭示了辣木叶通过多成分、多靶点、多通路协同发挥抗肥胖作用，为辣木叶抗肥胖及其分子机制的深入研究提供理论依据。

Abstract: Objects: In this study, the molecular targets and pathways of anti-obesity of the active ingredients of Moringa oleifera Lam. leaves were predicted and validated by network pharmacology and molecular docking techniques, and the anti-obesity effects of the active ingredients of Moringa oleifera Lam. leaves and their potential mechanisms were investigated. Methods: The active ingredient targets of Moringa oleifera Lam. leaves and obesity-related targets were obtained through PubChem, DisGeNET database and SwissADME, Swiss Target Prediction online prediction platform. The active ingredient targets and obesity-related targets were intersected by Venny 2.0.1 platform, and the key targets were screened out, then the PPI network analysis of the core targets was performed by STRING 11.0 database. The "component-target" interaction network was construct by Cytoscape 3.8.2 software, and the core active ingredients were screened out. GO functional enrichment and KEGG pathway analysis were performed on the core targets by the David database. Finally, molecular docking of pathway enrichment targets to core components was performed using Auto Dock 4.2 software. Results: Fifty active ingredients of Moringa oleifera Lam. leaves were screened, and a total of 126 core targets of Moringa oleifera Lam. leaves anti-obesity were identified, among which the main active ingredients were rhamnetin, cholest-5-en-3-ol, yangmeiin, lignan, etc. GO and KEGG analyses showed that the active ingredients of Moringa oleifera Lam. leaves exerted anti-obesity effects through multiple pathways such as HIF-1, insulin resistance, type 2 diabetes and insulin signalling pathway, and through biological processes such as positive regulation of RNA polymerase II promoter transcription, signalling, positive regulation of gene expression, negative regulation of protein phosphorylation and apoptotic expression. The molecular docking results showed that all 11 core components bound to the targets. Among them, PIK3R1 showed the lowest affinity with rhamnetin (−9.2 kcal/mol), followed by PIK3CA with cholest-5-en-3-ol (−9.1 kcal/mol), PIK3R1 with myricetin (−8.8 kcal/mol), and AKT1 with luteolin (−8.7 kcal/mol). Conclusion: The above results reveals that Moringa oleifera Lam. leaves could aganist obesity through multi-component, multi-target and multi-pathway mecanism. These results will provide a theoretical basis for the in-depth study of the anti-obesity of Moringa oleifera Lam. leaves and its molecular mechanism.