Unraveling the Multi-target Regulatory Network of Dahuang Zhechong Pill in Intestinal Fibrosis via Integrated Multi-omics and Computational Biology
- VernacularTitle: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
- Author:
Zhuxiu ZHOU
1
;
Jiong MA
;
Haibing HUA
;
Zhimin FAN
;
Desong KONG
;
Bao YUAN
Author Information
- Publication Type:Journal Article
- Keywords: Dahuang Zhechong pill; Intestinal fibrosis; Network pharmacology; Metabolomics; Molecular docking
- From: World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(10):2817-2835
- CountryChina
- Language:Chinese
- 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.
