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

Yangjie Liao; Xing Wu; Weiwei Luo; Jiang Chen; Yujun Huang; Kejia Ma; Chao Zhang; Jiayi Wang; Yan Yang; Minzi Deng; Xiaoyan Wang

doi:10.1021/acsomega.3c00210

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

ACS Omega. 2023 Apr 17;8(17):15217-15228. doi: 10.1021/acsomega.3c00210. eCollection 2023 May 2.

Authors

Yangjie Liao^{1

2}, Xing Wu^{1

2}, Weiwei Luo^{1

2}, Jiang Chen³, Yujun Huang^{1

2}, Kejia Ma^{1

2}, Chao Zhang^{1

2}, Jiayi Wang^{1

2}, Yan Yang^{1

2}, Minzi Deng¹, Xiaoyan Wang^{1

2}

Affiliations

¹ Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, China.
² Hunan Key Laboratory of Non Resolving Inflammation and Cancer, Changsha 410008, China.
³ The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, China.

Abstract

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.