目的:通过网络药理学和分子对接技术探讨珍宝丸“异病同治”治疗缺血性脑卒中和冠心病等心脑血管疾病的作用机制。方法:通过TCMSP、OMIM、GeneCards、DisGeNET数据库筛选珍宝丸治疗冠心病和缺血性脑卒中的潜在靶点,并通过STRING数据库进行PPI分析,使用Cytoscape 3.7.2软件对PPI网络进行拓扑分析,筛选出关键靶点。利用DAVID数据库进行GO和KEGG功能富集分析。通过构建“活性成分-靶点-通路”网络筛选出核心活性成分和核心靶点后,利用AutoDock Vina进行分子对接预测。结果:筛选后得到珍宝丸治疗冠心病和缺血性脑卒中的潜在靶点有74个;对PPI网络分析后得到10个关键靶点,包括TNF、IL-6、ALB、IL-1B、ICAM-1、TLR4、CXCL8、MMP9、TGFB1、PTGS2;GO和KEGG富集分析表明,与冠心病和缺血性脑卒中相关且排序靠前的通路有AGE-RAGE信号通路、脂质和动脉粥样硬化、流体剪切力与动脉粥样硬化等,主要与炎症反应、基因表达负调控、血管生成的正调控等生物过程有关。核心活性成分(2R)-7-羟基-5-甲氧基-N-乙酰色胺-黄酮类化合物-4-1、β-谷甾醇、谷甾醇、豆甾醇、甘草素与KDR、NOS2、PIK3CA、PPARG、PTGS2结合稳定。结论:基于网络药理学分析和分子对接的方法发现珍宝丸可以通过多靶点、多途径治疗冠心病和缺血性脑卒中,并且可能通过抗炎、抗氧化应激等作用,发挥“异病同治”效果。
Objective: To investigate the mechanism of action of Zhenbao Pill in the treatment of ischemic stroke and coronary heart disease through network pharmacology and molecular docking technology. Methods: The potential targets of Zhenbao Pill in the treatment of coronary heart disease and ischemic stroke were screened by TCMSP, OMIM, GeneCards and DisGeNET databases, and PPI analysis was performed by STRING database. Cytoscape 3.7.2 software was used to perform topological analysis of PPI network to screen out key targets. GO and KEGG functional enrichment analysis was performed using the DAVID database. After screening out the core active ingredients and core targets by constructing the 'active ingredient-target-pathway' network, AutoDock Vina was used for molecular docking prediction. Results: There were 74 potential targets of Zhenbao Pills in the treatment of coronary heart disease and ischemic stroke. Ten key targets were obtained after PPI network analysis, including TNF, IL-6, ALB, IL-1B, ICAM-1, TLR4, CXCL8, MMP9, TGFB1 and PTGS2. GO and KEGG enrichment analysis showed that the top-ranked pathways related to coronary heart disease and ischemic stroke were AGE-RAGE signaling pathway, lipid and atherosclerosis, fluid shear stress and atherosclerosis, which were mainly related to inflammatory response, negative regulation of gene expression, positive regulation of angiogenesis and other biological processes. The core active components (2R)-7-hydroxy-5-methoxy-N-acetyltryptamine-flavonoid-4-1, β-sitosterol, sitosterol, stigmasterol and liquiritigenin were stable with KDR, NOS2, PIK3CA, PPARG and PTGS2. Conclusion: Based on network pharmacology analysis and molecular docking, it is found that Zhenbao Pill can treat coronary heart disease and ischemic stroke through multiple targets and multiple pathways, and may play a role in 'treating different diseases with the same treatment' through anti-inflammatory and anti-oxidative stress.
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