基于网络药理学和分子对接的“黄连-黄芩-黄柏”治疗细菌性痢疾的潜在活性成分及其作用机制研究

Research on Potential Active Ingredients and Mechanism of Action of"Coptidis Rhizoma-Scuteliariae Radix-Phellodendri Chinensis Cortex"for the Treatment of Bacillary Dysentery Based on Network Pharmacology and Molecular Docking

目的:利用网络药理学方法和分子对接技术,分析“黄连-黄芩-黄柏”(简称“三黄”)治疗细菌性痢疾的潜在活性成分和作用机制,为后续的新药开发研究提供依据。方法:利用中药系统药理学平台(Traditional Chinese Medicine Systems Pharmacology Database,TCMSP)获取“三黄”的活性化合物及其潜在作用靶点,再从GeneCards、CTD、TTD和drugbank等数据库获取细菌性痢疾的疾病靶点,然后确定“三黄”治疗细菌性痢疾的潜在作用靶点,随后进行蛋白质-蛋白质相互作用(protein-protein interaction,PPI)分析,以筛选出核心靶点,进而通过GO功能分析和KEGG通路富集分析筛选“三黄”治疗细菌性痢疾的生物过程和相关通路,最后通过分子对接处理分析受体与配体间的亲和力。结果:借助TCMSP,共从“三黄”中筛选出87个关键活性成分,而其对应的作用靶点有228个,而在相关数据库中获取到细菌性痢疾的疾病靶点共313个,通过比较分析得到交集靶点34个;通过PPI分析,又从34个交集靶点中筛选得到14个核心靶点;通过KEGG通路富集分析发现,有14条治疗细菌性痢疾的重要信号通路;利用Cytoscape软件,根据34个交集靶点和14条重要信号通路,筛选得到度值最大的前5个活性成分依次为槲皮素、汉黄芩素、黄芩素、β-谷甾醇、异延胡索单酚碱;而分子对接结果显示,肿瘤坏死因子(TNF)、白介素-6(IL-6)和环氧合酶2(PTGS2)与槲皮素、汉黄芩素、黄芩素、β-谷甾醇、异延胡索单酚碱具有较好的亲和力(结合能<-5 kJ/mol)。结论:槲皮素、汉黄芩素、黄芩素、β-谷甾醇、异延胡索单酚碱可能是“三黄”治疗细菌性痢疾的主要潜在活性成分,而TNF、IL-6和PTGS2可能是其主要作用靶点。

Objective:To analyze the potential active ingredients and mechanism of action of"Coptidis rhizoma-Scuteliariae radix-Phellodendri chinensis cortex"for the treatment of bacillary dysentery by using network pharmacology methods and molecular docking technology,so as to provide a basis for subsequent research and development of new drugs.Methods:The active compounds and the potential targets of"Coptidis rhizoma-Scuteliariae radix-Phellodendri chinensis cortex"were acquired from Traditional Chinese Medicine Systems Pharmacology Database(TCMSP),and the disease targets of bacillary dysentery were acquired from the databases such as GeneCards,CTD,TTD and drugbank,then the potential targets of"Coptidis rhizoma-Scuteliariae radix-Phellodendri chinensis cortex"for the treatment of bacillary dysentery were identified.Subsequently,the protein-protein interaction(PPI)analysis was performed to screen the core targets,and the biological processes and related pathways of"Coptidis rhizoma-Scuteliariae radix-Phellodendri chinensis cortex"for the treatment of bacillary dysentery were screened by GO functional analysis and KEGG pathway enrichment analysis.Finally,the affinity between receptors and ligands was analyzed by molecular docking.Results:Through the TCMSP,a total of 87 key active ingredients were screened from"Coptidis rhizoma-Scuteliariae radix-Phellodendri chinensis cortex",and there were 228 corresponding targets.A total of 313 disease targets of bacillary dysentery were obtained in the relevant database,and 34 intersection targets were obtained through comparative analysis.By PPI analysis,14 core targets were screened from the 34 intersection targets.The KEGG pathway enrichment analysis showed that there were 14 important signaling pathways for the treatment of bacillary dysentery.By using the software Cytoscape and based on the 34 intersection targets and 14 important signaling pathways,the top five active ingredients with the largest degree were screened,which were quercetin,wogonin,baicalein,β-sitosterol,and isocorypalmine in sequence.The molecular docking results showed that the tumor necrosis factor(TNF),interleukin-6(IL-6)and cyclooxygenase 2(PTGS2)had good affinity to quercetin,wogonin,baicalein,β-sitosterol,and isocorypalmine(binding energy less than-5 kJ/mol).Conclusion:Quercetin,wogonin,baicalein,β-sitosterol,and isocorypalmine may be the main potential active ingredients of"Coptidis rhizoma-Scuteliariae radix-Phellodendri chinensis cortex"for the treatment of bacillary dysentery,and TNF,IL-6 and PTGS2 may be the main targets.