基于网络药理学和分子对接方法研究首荟通便胶囊治疗便秘的作用机制

基于网络药理学和分子对接方法探索首荟通便胶囊治疗便秘的作用机制。利用中药系统药理学分析平台(TCMSP)和中药分子机制的生物信息学分析工具(BATMAN),根据口服利用度(OB)≥30%、类药性(DL)≥0.18的筛选原则获取首荟通便胶囊中8味药材的化学成分和作用靶点;通过GeneCards,PharmGkb等数据库获取便秘相关靶点,药物靶点与疾病靶点取交集得到首荟通便胶囊治疗便秘的潜在作用靶点;采用STRING平台构建潜在靶点蛋白质相互作用(PPI)网络并获得GO分析及KEGG通路数据,进行富集分析预测其作用机制。运用Cytoscape 3.6.1软件构建"药材-化学成分-药物靶点"网络并对PPI网络进行网络拓扑分析。分子对接方法用以验证网络药理学分析首荟通便胶囊治疗便秘结果的准确性。PPI网络分析结果显示有槲皮素、豆甾醇、芦荟大黄素、大黄酸等92个化学成分,关键靶点有AKT1,MAPK1,IL6,JUN,TNF,TP53等。富集分析筛选出157条信号通路(P<0.01),主要涉及白细胞介素17信号通路、糖尿病并发症中的AGE-RAGE信号通路、甲状腺激素信号通路等;分子对接结果显示,度值排名前3的槲皮素、白藜芦醇和赖氨酸对接关键靶点的蛋白结晶复合物构象合理。该研究初步表明,首荟通便胶囊中多种活性成分通过作用于AKT1,MAPK1,IL6,JUN等关键靶点,调节多条信号通路,增加肠道的滑润度和蠕动功能,保证肠道管腔通畅,发挥治疗便秘的作用。

Mechanism of Shouhui Tongbian Capsules in treating constipation based on network pharmacology and molecular docking

To explore the mechanism of Shouhui Tongbian Capsules in treating constipation by means of network pharmacology and molecular docking approach.Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Bioinfoematics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN)were applied to obtain chemical components and potential targets of eight herbs in Shouhui Tongbian Capsules according to the screening principles of oral availability(OB)≥30%and drug-like property(DL)≥0.18.Disease targets relating to constipation were screened out through GeneCards,PharmGkb and other databases,drug targets were integrated with disease targets,and intersection targets were exactly the potential action targets of Shouhui Tongbian Capsules for treating constipation;PPI network of potential targets was constructed using STRING platform,and GO(gene ontology)analysis and KEGG(Kyoto encyclopedia of genes and genomes)pathway data were obtained to conduct enrichment analysis and predict its mechanism of action.Cytoscape 3.6.1 was used to construct a network of"medicinal materials-chemical components-drug targets",and the network topology analysis was carried out on the PPI network to obtain its main components and key targets.Molecular docking between components and key targets of Shouhui Tongbian Capsules verified the accuracy of network pharmacological analysis results.The PPI network analysis showed 92 chemical components,including quercetin,stigmaste-rol,aloe-emodin,rhein,and key targets for instance AKT1,MAPK1,IL6,JUN,TNF and TP53.The enrichment analysis of KEGG screened out 157 signal pathways(P<0.01),mainly involving interleukin 17 signaling pathway,AGE-RAGE signaling pathway in diabetic complications,thyroid hormone signaling pathway.Quercetin,resveratrol and lysine with top degree value had a rational conformation in docking site of protein crystal complexes.This study preliminarily showed that various active ingredients in Shouhui Tongbian Capsules could regulate multiple signaling pathways,increase intestinal smoothness and peristalsis function,ensure smooth intestinal lumen,and play a role in treating constipation by acting on key targets,such as AKT1,MAPK1,IL6 and JUN.