“半夏-黄连”药对防治化疗相关性腹泻的网络药理学研究

Network Pharmacologic Study on the Mechanism of"Banxia-Huanglian"in the Treatment of Chemotherapy-induced Diarrhea

目的运用网络药理学方法探寻“半夏-黄连”药对防治化疗相关性腹泻(CID)的作用机制。方法利用中药系统药理学数据库与分析平台(TCMSP,https://tcmspw.com/tcmsp.php)、中医药百科全书数据库(ETCM,http://www.tcmip.cn/ETCM/)检索药物主要有效成分并筛选药物相关靶点,通过GeneCards数据库(https://www.genecards.org/)收集CID相关疾病基因,并将药物靶点与疾病基因进行韦恩分析得出交集基因靶点,在DAVID数据库(https://david.ncifcrf.gov/)和KEGGMapper数据库(https://www.genome.jp/kegg/mapper/color.html)进行富集分析,通过Cytoscape软件构建“中药-有效成分-靶点-通路”的多层次网络,筛选出核心基因。结果半夏-黄连药对主要有效成分39个,包含269个靶点。CID基因靶点有603个,其中117个是半夏-黄连药对治疗CID的潜在靶点。通过GO功能分析和KEGG通路富集分析发现半夏-黄连药对治疗CID是通过IL-17、MAPK、TNF及PI3K/Akt信号通路发挥抗炎和抗肿瘤作用。半夏-黄连药对治疗CID的关键基因靶点为TP53、Akt1、JUN、TNF、HSP90AA1、IL-6、EGFR等。结论本研究通过网络药理学方法发现“半夏-黄连”药对防治CID具有多靶点、多通路的治疗机制,为临床使用中医辛开苦降法治疗CID提供了理论基础。

Objective:To study the mechanism of"Banxia-Huanglian"herb pair on chemotherapy-induced diarrhea(CID)by network pharmacology.Methods:TCMSP and ETCM databases were used to retrieve the main active ingredients of drugs and screen drug-related targets.CID-related disease genes were collected through the GeneCards database,and the drug targets and disease genes were analyzed by Venn to obtain the intersection gene targets.The DAVID and KEGGMapper database were used for enrichment analysis,and the multi-level network of"herb-ingredient-target-pathway"was constructed by Cytoscape software,and the core genes were screened out.Results:"Banxia-Huanglian"herb pair had 39 main active ingredients,including 269 targets.There were 603 CID gene targets in total,of which 117 were potential targets of Banxia-Huanglian herb pair for the treatment of CID.Through GO function analysis and KEGG pathway enrichment analysis,it was found that"Banxia-Huanglian"herb pair in the treatment of CID exerted anti-inflammatory and anti-tumor effects through IL-17,MAPK,TNF and PI3K/Akt signaling pathways.The key gene targets of“Banxia—Huanglian”herb pair in the treatment of CID were TP53,Aktl,JUN,TNF,HSP90AA1,IL-6,and EGFR,etc.Conclusion:In this study,it was discovered through network pharmacology that"Banxia-Huanglian''has a multi-target and multi-pathway therapeutic mechanism for CID,which provides a theoretical basis for the clinical use of traditional Chinese medicine method of Xinkai Kujiang to treat CID.