基于网络药理学和分子对接探讨桃红四物汤“异病同治”原发性痛经和2型糖尿病的有效成分及作用机制

Based on network pharmacology and molecular docking,the effective components and mechanism of Taohong Siwu Decoction for Primary dysmenorrhea and Type 2 diabetes

目的:通过网络药理学和分子对接探讨桃红四物汤“异病同治”原发性痛经和2型糖尿病的有效成分及作用机制。方法:利用生物科学与网络药理学平台、蛋白数据库和String数据库搜集桃红四物汤化学成分及其靶点数据;基于筛选得到的靶点,进行GO富集功能(gene ontology,GO)和KEGG通路富集分析(Kyoto encyclopedia of genes and genomes,KEGG);构建“药物-成分-靶点-疾病-通路”网络图;同时将筛选得到的关键有效成分和核心靶点进行分子对接验证。结果:从桃红四物汤中筛选出44个活性成分涉及195个靶点、2型糖尿病疾病靶点1421个,原发性痛经疾病靶点650个,药物与疾病的交集靶点36个。β-谷甾醇、山柰酚、槲皮素、豆甾醇、木犀草素匹配到较多靶点。核心靶点蛋白涉及白细胞介素6、白细胞介素1、RAC-α丝氨酸/苏氨酸蛋白激酶、肿瘤坏死因子-α、过氧化物酶体增生激活受体γ、肿瘤蛋白等;GO条目1021条,分子生物学功能(MF)954条、细胞学组分(CC)20条和生物学过程(BP)47条,KEGG通路富集得到通路121条,主要作用于癌症、糖尿病并发症的AGE-RAGE信号通路、人巨细胞病毒感染、卡波济肉瘤相关疱疹病毒感染、乙型肝炎、IL-17信号通路、HIF-1信号通路、TNF信号通路、P53信号通路、PI3K-Akt信号通路等多种途径。分子对接结果显示主要活性成分与靶点均能自发结合。结论:构建“药物-成分-靶点-疾病-通路”网络图,探讨桃红四物汤防治PD和T2DM的潜在靶点和活性组分,运用分子对接技术,探索其多成分与多靶点、多疾病关系,从而揭示其潜在有效成分和作用机制。

Objective:To explore the effective components and mechanism of Taohong Siwu Decoction for Primary dysmenorrhea and Type 2 diabetes through network pharmacology and molecular docking.Method:Using biological science and network pharmacology platforms,protein databases,and String databases to collect chemical composition and related target data of Taohong Siwu Tang;Based on the screened targets,perform GO enrichment function(GO)and KEGG pathway enrichment analysis(KEGG);Construct a network diagram of"drugs components targets diseases pathways";At the same time,molecular docking verification will be carried out on the selected key active ingredients and core targets.Results 44 active ingredients were screened from Taohong Siwu Decoction,involving 195 related targets,1421 targets for Type 2 diabetes,650 targets for Primary dysmenorrhea,and 36 targets for intersection of drugs and diseases.amongβ-Glutinosterol,kaempferol,quercetin,stigmasterol,and luteolin have been matched to multiple targets.Core target proteins involve interleukin-6,interleukin-1,and RAC-αSerine/threonine protein kinase,tumor necrosis factor,peroxisome proliferation activated receptorγ、Tumor proteins,etc;1021 GO entries,954 molecular biological function(MF)entries,20 cytological components(CC)entries and 47 biological processes(BP)entries,121 KEGG pathways were enriched,mainly acting on AGE-RAGE signaling pathway,human cy-tomegalovirus infection,Kaposi sarcoma associated herpesvirus infection,hepatitis B,IL-17 signaling pathway,HIF-1 signaling pathway,TNF signaling pathway,P53 signaling pathway Multiple pathways such as PI3K-Akt signaling pathway.The molecular docking results show that the main active ingredients can spontaneously bind to the target.Conclusion:Construct a"drug component target disease pathway"network diagram to explore the potential targets and active components of Taohong Siwu Tang in the prevention and treatment of PD and T2DM.Using molecular docking technology,explore the relationship between its multiple components,multiple targets,and multiple diseases,thereby revealing its potential effective components and mechanism of action.