基于网络药理学及分子对接探究益母草碱治疗肠道炎症的分子机制

doi:10.16431/j.cnki.1671-7236.2023.05.037

摘要/Abstract

摘要： 【目的】运用网络药理学、分子对接和动力学模拟技术研究益母草碱治疗肠道炎症的分子机制。【方法】采用Pubchem、PharmMapper和SwissTargetPrediction数据库收集益母草碱与肠道炎症的潜在靶点,利用Venny 2.1在线作图工具平台系统获取益母草碱治疗肠道炎症的交集靶点;通过STRING与DAVID数据库获取蛋白-蛋白相互作用(PPI)关系并绘制交集靶点的PPI网络图,对交集靶点进行GO功能与KEGG通路富集分析,运用Cytoscape 3.8.2软件筛选得到核心靶点蛋白,应用分子对接技术与分子动力学模拟对核心靶点进行验证。【结果】共收集到379个与益母草碱相关的潜在靶点蛋白,15 464个与肠道炎症相关的潜在靶点,获得170个益母草碱治疗肠道炎症的潜在交集靶点,筛选出丝氨酸/苏氨酸蛋白激酶1(AKT1)、抑癌基因TP53、前列腺素氧化环化酶2(PTGS2)、雷帕霉素靶蛋白(mTOR)、多聚ADP核糖聚合酶1(PARP1)等16个核心靶点。GO功能及 KEGG通路富集分析结果显示,益母草碱通过调控蛋白质磷酸化、细胞增殖、凋亡过程负调控、蛋白水解、炎症反应等144个生物过程和Fc epsilon RI信号通路、Fc γ-R介导的吞噬作用、MAPK信号通路、mTOR 信号通路等55条信号通路治疗肠道炎症。分子对接结果表明,益母草碱与核心靶点中PTGS2、mTOR、PARP1对接结果良好,有较强的结合活性,分子动力学模拟发现益母草碱与3个蛋白之间主要以氢键和疏水键相结合。【结论】益母草碱通过mTOR、PARP1、PTGS2等多个靶点,多个信号通路、多途径发挥其对肠道炎症的治疗效果。本研究结果为益母草碱在临床中的应用奠定基础。

关键词: 益母草碱; 肠道炎症; 网络药理学; 分子对接; 分子动力学模拟; 作用机制

Abstract: 【Objective】 The molecular mechanism of leonurine in the treatment of intestinal inflammation was investigated using network pharmacology,molecular docking and kinetic simulation techniques.【Method】Pubchem,PharmMapper and SwissTargetPrediction database were used to collect the potential targets of leonurine and intestinal inflammation,and obtain the intersection targets of leonurine in the treatment of intestinal inflammation in the Venny 2.1 online mapping tool platform system.The protein-protein interaction (PPI) relationship was obtained through STRING and DAVID databases,and the PPI network diagram of the intersection target was drawn.The GO function and KEGG pathway enrichment analysis of the intersection target was carried out,and the core target protein was screened by Cytascape 3.8.2 software.The core target was verified by molecular docking technology and molecular dynamics simulation.【Result】 A total of 379 potential target proteins related to leonurine and 15 464 potential targets related to intestinal inflammation were collected.170 potential intersection targets of leonurine for the treatment of intestinal inflammation were obtained.16 core targets including serine/threonine protein kinase 1(AKT1),tumor suppressor genes TP53,prostaglandin-endoperoxide synthase 2(PTGS2),mechanistic target of rapamycin (mTOR),poly ADP-ribose polymerase 1 (PARP1),etc. were screened.The results of GO function and KEGG pathway enrichment analysis showed that leonurine regulated 144 biological processes such as protein phosphorylation,cell proliferation,negative regulation of apoptosis,proteolysis,and inflammation,as well as 55 signal pathways,such as Fc epsilon RI signaling pathway and Fc γ-R-mediated phagocytosis including MAPK signaling pathway and mTOR signaling pathway to treat intestinal inflammation.Molecular docking results showed that leonurine had good docking results with the core targets PTGS2,mTOR and PARP1,and had strong binding activity.Molecular dynamics simulations had found that leonurine was mainly bound to the three proteins by hydrogen and hydrophobic bonds.【Conclusion】 Leonurine exerted its therapeutic effect on intestinal inflammation through multiple targets such as mTOR,PARP1 and PTGS2,and multiple signaling pathways and multiple pathways.The result of this study laid a foundation for the clinical application of leonurine.

Key words: leonurine; intestinal inflammation; network pharmacology; molecular docking; molecular dynamics simulation; action mechanism

中图分类号:

S859.7

许丞惠, 张旭梅, 杨彤, 李嘉蕙, 孙亚伟, 史慧君, 付强, 杨莉. 基于网络药理学及分子对接探究益母草碱治疗肠道炎症的分子机制[J]. 中国畜牧兽医, 2023, 50(5): 2103-2113.

XU Chenghui, ZHANG Xumei, YANG Tong, LI Jiahui, SUN Yawei, SHI Huijun, FU Qiang, YANG Li. Molecular Mechanism of Leonurine in the Treatment of Intestinal Inflammation Based on Network Pharmacology and Molecular Docking[J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(5): 2103-2113.

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