基于分子对接和网络药理学探讨消栓肠溶胶囊改善血管内皮功能的作用机制

doi:10.3969/j.issn.1673-5765.2021.10.013

摘要/Abstract

摘要： 目的应用分子对接和网络药理学方法，预测消栓肠溶胶囊改善血管内皮功能的潜在靶点及信号通路。方法通过中药系统药理学数据库与分析平台（traditional Chinese medicine systems pharmacology database and analysis platform，TCMSP）数据库检索消栓肠溶胶囊的主要活性化合物，并筛选出中药活性成分的作用靶点；借助GeneCards、在线人类孟德尔遗传（online Mendelian inheritance in man，OMIM）等数据库获取血管内皮功能障碍的相关靶标。利用STRING数据库和Cytoscape 3.8.0软件构建药物-化合物-靶点网络、蛋白互作（protei n-protein interaction，PPI）网络。最后对核心靶点进行GO富集、京都基因和基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）通路分析，借助AutoDock分子模拟软件进行分子对接。结果根据筛选条件得到消栓肠溶胶囊66个活性化合物和218个药物靶点，消栓肠溶胶囊与血管内皮功能障碍共同靶点基因159个，拓扑分析结果包含5个关键靶点。通过GO分析得出2700个生物过程，通过KEGG通路富集分析得出168条信号通路。分子对接研究结果显示消栓肠溶胶囊化学成分与关键靶点具有较好的结合活性。结论消栓肠溶胶囊可能通过作用于TP53、MAPK1、JUN、Akt1、MAPK8等关键靶点，调控磷脂酰肌醇3-激酶（phosphatidylinositol 3-kinase，PI3K）/Akt信号通路、流体剪切应力和动脉粥样硬化、糖尿病并发症晚期糖基化终末产物（advanced glycation end product，AGE）与其受体（receptor for AGE，RAGE）信号通路、IL-17信号通路、TNF-α信号通路、凋亡、Th17细胞分化、TP53信号通路等，调节血流动力、抗凋亡、抗炎、保护血管及促进血管新生，从而发挥改善血管内皮功能的作用。

文章导读： 本研究通过TCMSP等中药数据库，GeneCards、OMIM等生物信息数据库，基于分子对接和网络药理学分析了消栓肠溶胶囊改善血管内皮细胞功能的可能靶点及可能机制，有助于后续针对消栓肠溶胶囊的基础研究和临床应用。

关键词: 分子对接; 消栓肠溶胶囊; 血管内皮功能; 信号通路

Abstract: Objective To investigate the potential targets and signaling pathways in the improvement of vascular endothelial function using molecular docking and network pharmacology methods. Methods The traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) database was searched for the literatures involving the main active compounds of xiaoshuan enteric-coated capsule, and the targets of active pharmaceutical ingredients were screened out. The related targets for vascular endothelial dysfunction were obtained by searching the GeneCards, online Mendelian inheritance in man (OMIM) databases. The STRING database and Cytoscape 3.8.0 software were used to construct the drug-compound-target network and target protein-protein interaction (PPI) network. Finally, GO enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were performed on the core targets, and molecular docking was performed with the help of AutoDock software.

Results A total of 66 active compounds and 218 drug targets were obtained, 159 common target

genes for xiaoshuan enteric-coated capsule and vascular endothelial dysfunction were identified, and 5 key targets were identified by the topological analysis. The GO analysis yielded 2700 biological processes, and the KEGG pathway enrichment analysis yielded 168 signaling pathways. The results of molecular docking study showed that the chemical compositions of xiaoshuan enteric-coated capsule had good binding activity to the key targets. Conclusions By acting on TP53, MAPK1, JUN, Akt1, MAPK8 and other key targets, xiaoshuan enteric-coated capsule may regulate phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, fluid shear stress and atherosclerosis, advanced glycation end products (AGE) and receptors for AGE (RAGE) signaling pathway in diabetic complications, IL-17 signaling pathway, TNF-α signaling pathway, apoptosis signaling pathway, Th17 cell differentiation, TP53 signaling pathway, etc., and thus play a role in improving vascular endothelial function by regulating blood flow dynamics, anti-apoptosis, anti-inflammation, vascular protection and promotion of neovascularization.

Key words: Molecular docking; Xiaoshuan enteric-coated capsule; Vascular endothelial function; Signaling pathway

聂玉婷, 温璐璐, 司童, 刘瑶, 高利, 曲淼. 基于分子对接和网络药理学探讨消栓肠溶胶囊改善血管内皮功能的作用机制[J]. 中国卒中杂志, 2021, 16(10): 1050-1058.

NIE Yu-Ting, WEN Lu-Lu, SI Tong, LIU Yao, GAO Li, QU Miao. Mechanism of Xiaoshuan Enteric-Coated Capsule in Improvement of Vascular Endothelial Function Based on Molecular Docking and Network Pharmacology[J]. Chinese Journal of Stroke, 2021, 16(10): 1050-1058.

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