世界科学技术-中医药现代化2025，Vol.27Issue(10)：2817-2835,19.DOI:10.11842/wst.20241227005
基于多组学整合与计算生物学技术探究大黄蛰虫丸干预炎症性肠病肠纤维化的多靶点调控网络
Unraveling the Multi-target Regulatory Network of Dahuang Zhechong Pill in Intestinal Fibrosis via Integrated Multi-omics and Computational Biology
摘要
Abstract
Objective To explore the anti-intestinal fibrosis mechanism of Dahuang Zhechong pill.Methods Based on the network pharmacology method,the traditional Chinese medicine systems pharmacology database and analysis platform,SwissTargetPrediction database and metabolomics technology was used.OmicsNet 2.0 platform combined with the findings of network pharmacology and metabolomics,and molecular simulation docking and molecular biology methods were used to study the mechanism of anti-intestinal fibrosis of Dahuang Zhechong pill.Results Dahuang Zhechong pill contains 142 potential active ingredients and 855 anti-intestinal fibrosis targets.The 10 core ingredients(quercetin,acacetin,oroxylin a,kaempferol,moslosooflavone,panicolin,etc.)may play a role in regulating lipid metabolism and atherosclerosis,EGFR tyrosine kinase inhibitor resistance,HIF-1 signaling pathway,TNF signaling pathway and IL-17 signaling pathway.Metabolomics results showed that 59 endogenous substances(oxaloacetic acid,ethylthioisonicamide,6-benzylaminopurine,tyrosine and cortisol,etc.)may be the key metabolites of this drug against intestinal fibrosis.Central carbon metabolism,TCA cycle and amino acid metabolism were the key mechanisms,EGFR,AKT1,MAPK1,PTPN11,CASP3,PPARG,MET and PDGFRB may be the core targets.Dahuang Zhechong pill could significantly improve the levels of colorectal edema,inflammatory factors,inflammatory cell infiltration,collagen fiber deposition and α-SMA expression in mice with intestinal fibrosis,reduce the expression levels of pro-inflammatory factors IL-17 and IL-23 in serum,and increase the level of anti-inflammatory factor IL-10.Molecular dynamics simulations demonstrated stable conformational binding between core active ingredients and key targets.Conclusion Dahuang Zhechong pill may regulate EGFR/AKT1/MAPK mediated metabolism-inflammation interaction network through flavonoid components,and can improve intestinal fibrosis in multiple dimensions through molecular validation.关键词
大黄蛰虫丸/肠纤维化/网络药理学/代谢组学/分子对接Key words
Dahuang Zhechong pill/Intestinal fibrosis/Network pharmacology/Metabolomics/Molecular docking分类
医药卫生引用本文复制引用
周竹秀,马炯,花海兵,樊志敏,孔德松,袁保..基于多组学整合与计算生物学技术探究大黄蛰虫丸干预炎症性肠病肠纤维化的多靶点调控网络[J].世界科学技术-中医药现代化,2025,27(10):2817-2835,19.基金项目
无锡市卫生健康委员会中青年拔尖人才资助计划(HB2023108):经典名方大黄蛰虫丸治疗炎症性肠病肠道纤维化的作用机制研究,负责人:袁保 （HB2023108）
江阴市科学技术局科技创新专项基金项目(JY0603A011014220057PB):经典名方大黄蛰虫丸治疗炎症性肠病肠道纤维化的作用机制及对炎症性肠病肠道菌群影响的相关机制研究,负责人:袁保. （JY0603A011014220057PB）
