基于网络药理学方法探讨白术黄芪汤干预溃疡性结肠炎的作用机制研究

The Study on the Mechanism of Baizhu Huangqi Recipe in the Treatment of Ulcerative Colitis Based on Network Pharmacology

目的:该研究利用网络药理学的方法,探讨白术黄芪汤治疗溃疡性结肠炎(UC)的作用机制。方法:基于中药系统药理学数据库和分析平台(TCMSP)筛选出白术黄芪汤所含中药成分以及其所作用的靶点,并在STRING11.0平台上搜索相关基因。通过GAD、OMIM、CTD数据库获得溃疡性结肠炎的相关靶点。然后通过VENNY平台获得两者靶点交集。然后通过Cytoscape3.7.1构建出蛋白互作图。最后通过DAVID平台搜集到的靶点蛋白从生物过程(BP)、分子功能(MF)和细胞组分(CC)三方面进行基因本体功能功能富集分析和KEGG通路分析。结果:从TCMSP数据库筛选出白术黄芪汤的119种化学成分,其中预测到58个靶点,通过CTD、OMIM、GeneCards预测到4356个与溃疡新结肠炎相关的靶点,韦恩图显示29个潜在靶标交集。基因本体富集分析(GO分析)结果显示:其生物作用包括对细胞内外各种物质及刺激的反应、对细胞免疫的积极调控等方面。其细胞功能包括对细胞周期蛋白A2-CDK2复合物、细胞质、细胞核及质膜区的调控。其分子功能包括对蛋白磷酸酶结合、一氧化氮合酶调节剂活性、蛋白质结构域特异性结合、离子结合及核受体活性等方面的调控。KEGG结果分析表明:白术黄芪汤主要对PI3K-Akt信号通路、细胞衰老、IL-17信号通路及VEGF信号通路发挥治疗UC的效用。结论:本文从网络药理学角度发现白术黄芪汤治疗UC的机制是多靶点、多通路的复杂过程,其机制与调节免疫反应、炎症反应、抗肿瘤等相关通路有关。

Objective:To explore the mechanism of Baizhu Huangqi Decoction in the treatment of ulcerative colitis with the method of network pharmacology.Methods:Based on the Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP),the Chinese medicine components contained in Baizhu Huangqi Decoction and their targets were screened out,and related genes were searched on STRING 11.0 platform.Relevant targets of ulcerative colitis were obtained through GAD,OMIM and CTD databases.Then the intersection of the two targets was obtained through the VENNY platform.Then the protein interaction map was constructed by Cytoscape 3.7.1.Finally,the target protein collected through the DAVID platform was used for gene ontology function enrichment analysis and KEGG pathway analysis from three aspects:biological process(BP),molecular function(MF),cellular component(CC).Results:119 chemical components of Baizhu Huangqi Decoction were screened from TCMSP database,of which 58 targets were predicted,and 4356 targets related to ulcerative new colitis were predicted by CTD,OMIM,GeneCards,and the Wayne diagram showed 29 potential targets intersection.The results of GO analysis showed that its biological effects included the response to various substances and stimuli inside and outside the cell,and the positive transformation of cellular immunity.Its cell functions included the decomposition of cyclin A2-CDK2 complex,cytoplasm,nucleus and plasma membrane area.Its molecular functions included changes in protein phosphatase binding,nitric oxide synthase modulator activity,protein domain conversion binding,ion binding,nuclear receptor activity,etc.Decoction mainly played a role in the treatment of UC for tumor-related pathways,PI3K-Akt signaling pathway,gastric cancer,cell aging,IL-17 signaling pathway,neurotrophin signaling pathway,and VEGF signaling pathway.Conclusion:From the perspective of network pharmacology,it is found that the mechanism of Baizhu Huangqi Decoction in treating UC is a complex process of multiple targets and multiple pathways,and its mechanism is related to the regulation of immune response,inflammatory response,anti-tumor and other related pathways.