基于网络药理学的济川煎治疗便秘的作用机制研究

Research with Network Pharmacology of the Pharmacologic Mechanism of Jichuan Decoction on Constipation

目的:基于网络药理学方法研究济川煎治疗便秘的药理机制及作用靶点。方法:使用中药系统药理学数据库与分析平台(TCMSP)筛选济川煎中6味中药的化学成分及其作用靶点,通过GeneCards、OMIM、TTD、DisGeNET、Drugbank数据库查询便秘的疾病靶点;利用R语言筛选成分和疾病的交集靶点,利用STRING数据库构建靶点蛋白互作网络;运用Cytoscape(3.8.0)软件构建中药-化学成分-便秘疾病靶点网络图;利用R语言对靶基因进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。结果:筛选出槲皮素、山柰酚、汉黄芩素、β-谷甾醇、柚皮素、黄芩素6个主要化学成分,PTGS2、PTGS1、NCOA2、SCN5A、ADRB2、AR 6个关键靶点,GO富集分析显示靶点相关功能主要涉及对脂多糖的反应、对细菌来源分子的反应、对氧化应激的反应等,KEGG富集分析显示靶点相关通路主要涉及药物代谢-细胞色素P450、细胞色素P450对异生素的代谢、视黄醇代谢等。结论:济川煎可能通过多靶点、多通路协同作用,发挥抗炎、抗氧化等作用,从而改善便秘。

Objective:To investigate the pharmacological mechanisms and action targets of Jichuan Decoction in the treatment of constipation based on a network pharmacology approach.Methods:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)were used to screen the chemical components and action targets of 6 Chinese medicinals in Jichuan Decoction.The disease targets of constipation were queried through Genecards,OMIM,TTD,DisGeNET,DRUGBANK databases.The intersection targets of ingredients and diseases were screened using the R(4.0.3).STRING database was used to construct the target protein interaction network.The network diagram of TCM chemical component and constipation disease target was constructed using Cytoscape(3.8.0)software.The GO enrichment analysis and KEGG enrichment analysis of target genes were performed using R language.Results:A total of 6 main chemical compounds include quercetin,kaempferol,wogonin,β-sitosterol,naringenin,and baicalein.A total of 6 key targets were PTGS2,PTGS1,NCOA2,SCN5A,ADRB2 and AR.GO enrichment analysis showed that the target-related functions mainly involved in response to lipopolysaccharide,response to molecule of bacterial origin,response to oxidative stress etc.And the KEGG enrichment analysis showed that the target-related pathways mainly involved in drug metabolism-cytochrome P450,metabolism of xenobiotics by cytochrome P450,Retinol metabolism,etc.Conclusion:Jichuan Decoction may relieve constipation by exerting anti-inflammatory,antioxidant,and other effects through multi-target and multi-pathway synergistic effects.