摘要: |
目的:基于网络药理学探讨补阳还五汤异病同治高脂血症和缺血性脑卒中的作用机制。方法:运用TCMSP数据库筛选补阳还五汤的活性成分并分析其作用靶点,采用Network Analyzer分析补阳还五汤的主要活性成分;检索OMIM、DrugBank、GeneCards、TTD、DisGeNET数据库,筛选出高脂血症和缺血性脑卒中的相关靶点;使用Biogenet对药物与两种疾病靶点进行蛋白质-蛋白质相互作用(PPI)网络构建,再提取三者的交集网络,得到补阳还五汤异病同治高脂血症和缺血性脑卒中的核心靶点;使用 Metascape 对核心靶点进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析,最后将筛选出的主要活性成分与核心靶点进行分子对接。结果:获取补阳还五汤活性成分77种、靶点250个,高脂血症靶点1074个、缺血性脑卒中靶点1211个,最终得到核心靶点96个、富集通路150条。补阳还五汤异病同治高脂血症和缺血性脑卒中的作用成分为槲皮素、β-谷甾醇、山柰酚、棕榈酸、豆甾醇等,核心靶点为肿瘤蛋白P53(TP53)、纤连蛋白-1、泛素蛋白,主要通路可能有磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)信号通路、脂质和动脉粥样硬化、白细胞介素-17信号通路等。分子对接结果显示,各个成分与靶点均能较好地结合,其中β-谷甾醇与TP53靶点的结合强度最佳。结论:补阳还五汤通过多活性成分、多作用靶点、多有效通路发挥对高脂血症和缺血性脑卒中的异病同治作用。 |
关键词: 高脂血症 缺血性脑卒中 异病同治 补阳还五汤 分子机制 |
DOI: |
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Mechanism of action of Buyang Huanwu decoction in homotherapy for heteropathy for hyperlipidemia and ischemic stroke:A study based on network pharmacology |
SUN Hanming,LI Xi,WANG Min,GAO Ying |
(The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine/National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion,Tianjin 301617,China) |
Abstract: |
Objective:To investigate the mechanism of action of Buyang Huanwu decoction in homotherapy for heteropathy for hyperlipidemia and ischemic stroke based on network pharmacology. Methods:TCMSP database was used to obtain the active components of Buyang Huanwu decoction and analyze their action targets,and Network Analyzer was used to investigate the main active components of Buyang Huanwu decoction. OMIM,DrugBank,GeneCards,TTD,and DisGeNET databases were searched to obtain the targets associated with hyperlipidemia and ischemic stroke. Biogenet was used to establish a protein-protein interaction network for the targets of the drug and the two diseases,and the three groups of targets were intersected to establish a network to obtain the core targets of Buyang Huanwu decoction in homotherapy for heteropathy for hyperlipidemia and ischemic stroke. Metascape was used to perform the gene ontology functional enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of core targets,and finally molecular docking was performed between the main active components and the core targets. Results:A total of 77 active components and 250 targets were obtained for Buyang Huanwu decoction,and there were 1074 targets for hyperlipidemia and 1211 targets for ischemic stroke. Finally,96 core targets and 150 pathways were obtained. As for Buyang Huanwu decoction in homotherapy for heteropathy for hyperlipidemia and ischemic stroke,the main active components included quercetin,beta-sitosterol,kaempferol,palmitic acid,and stigmasterol; the core targets were tumor protein P53 (TP53),fibronectin-1,and ubiquitin; the main pathways included the PI3K/Akt signaling pathway,lipid and atherosclerosis,and the interleukin-17 signaling pathway. Molecular docking showed good binding activity between the components and targets,with the strongest binding activity between beta-sitosterol and TP53. Conclusion:Buyang Huanwu decoction exerts a therapeutic effect of homotherapy for heteropathy in the treatment of hyperlipidemia and ischemic stroke through multiple active components,action targets,and effective pathways. |
Key words: hyperlipidemia ischemic stroke homotherapy for heteropathy Buyang Huanwu decoction molecular mechanism |