基于网络药理学和分子对接探讨厚朴排气合剂治疗慢性便秘潜在作用机制

Potential mechanism of Houpo Paiqi Mixture in treatment of chronic constipation based on network pharmacology and molecular docking

目的通过网络药理学和分子对接技术对厚朴排气合剂治疗慢性便秘的潜在作用机制进行研究。方法通过TCMSP数据库及文献补充获得厚朴排气合剂活性成分及作用靶点,OMIM、GeneCards、TTD、DrugBank数据库检索慢性便秘疾病靶点,将成分靶点及疾病靶点取交集后获得潜在靶点。采用Metascape数据库,以P<0.05为筛选条件,进行基因本体(GO)功能及京都基因和基因组百科全书(KEGG)分析,并利用Autodock软件对关键作用靶点和活性成分进行分子对接。结果共获得56种活性成分,厚朴排气合剂治疗慢性便秘共有217个靶点,其中关键靶点为蛋白激酶B1(Akt1)、肿瘤蛋白p53(TP53)、白细胞介素-6(IL-6)、半胱氨酸蛋白水解酶3(CASP3)、血管内皮生长因子A(VEGFA)、转录因子AP-1(JUN)、白细胞介素-1B(IL-1B)、MYC、表皮生长因子受体(EGFR)、丝裂原激活的蛋白激酶3(MAPK3)等。生物过程有5880条富集结果,分子功能有1083条富集结果,细胞组成有540条富集结果;KEGG通路主要包括癌症相关通路、磷脂酰肌醇3-激酶(PI3K)/Akt信号通路、细胞衰老等。分子对接显示厚朴排气合剂的主要活性成分与关键靶点具有良好的结合能力。结论厚朴排气合剂通过多途径、多靶点、多通路治疗慢性便秘,其机制与抑制炎症反应、抗衰老、调节平滑肌运动等有关。

Objective To study the potential mechanism of Houpo Paiqi Mixture in treatment of chronic constipation through network pharmacology and molecular docking techniques.Methods The active ingredients and their target were obtained through TCMSP database and literature supplement.OMIM,GeneCards,TTD,and DrugBank databases searched the disease targets of chronic constipation,and the potential targets were obtained after the intersection of the component targets and disease targets.Metascape database and P<0.05 were used to analyze gene ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG),and Autodock software was used for molecular docking of key action targets and active ingredients.Results A total of 56 active ingredients were obtained,and there were 217 targets for the treatment of chronic constipation,among which the key targets were Aktl,TP53,IL-6,CASP3,VEGFA,JUN,IL-1B,MYC,EGFR,MAPK3,etc.There were 5880 enrichment results for biological processes,1083 enrichment results for molecular functions,and 540 enrichment results for cell composition.KEGG pathway mainly includes cancer-related pathway,PI3K/Akt signaling pathway,and cell aging.Molecular docking showed that the main active components of Houpu exhaust mixture had good binding ability with key targets.Conclusion Houpo Paiqi Mixture can treat chronic constipation through multiple channels,multiple targets and multiple pathways,and its mechanism may be related to inhibiting inflammation,antiaging and regulating smooth muscle movement.