Azelaic Acid Regulates the Renin–Angiotensin System and Improves Colitis Based on Network Pharmacology and Experimentation

• Published in: ACS omega 2023-05, Vol.8 (17), p.15217-15228
• Main Authors: Liao, Yangjie, Wu, Xing, Luo, Weiwei, Chen, Jiang, Huang, Yujun, Ma, Kejia, Zhang, Chao, Wang, Jiayi, Yang, Yan, Deng, Minzi, Wang, Xiaoyan
• Format: Article
• Language: English
• ISSN: 2470-1343; 2470-1343
• DOI: 10.1021/acsomega.3c00210

Inflammatory bowel disease (IBD), which encompasses Crohn’s disease and ulcerative colitis, has a complicated etiology that might be brought on by metabolic dysbiosis. Previous metabonomic studies have found a correlation between decreased azelaic acid (AzA) and IBD. Herein, data from the Metabolomics Workbench showed that the content of AzA decreased in IBD patients (PR000639) and dextran sulfate sodium (DSS)-induced mice (PR000837). The effects of AzA on IBD were then examined using a DSS-induced mouse model, and the results demonstrated that AzA alleviated clinical activity, decreased pro-inflammatory cytokine production, and reduced CD4+CD25+Foxp3+Treg percentages in mesenteric lymph nodes. Through network pharmacology analysis, we discovered 99 candidate IBD-associated genes that are potentially regulated by AzA. After the enrichment analysis of the candidate genes, the renin–angiotensin system (RAS) pathway was one of the most substantially enriched pathways. Additionally, AzA reversed the increased expression of important RAS components (ACE, ACE2, and MAS1L) following DSS induction, suggesting that AzA exerts therapeutic effects possibly via the RAS pathway. This study suggests that AzA may be a promising drug for treating IBD.