Liao Yangjie, Wu Xing, Luo Weiwei, Chen Jiang, Huang Yujun, Ma Kejia, Zhang Chao, Wang Jiayi, Yang Yan, Deng Minzi, Wang Xiaoyan
Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha 410013, China.
Hunan Key Laboratory of Non Resolving Inflammation and Cancer, Changsha 410008, China.
ACS Omega. 2023 Apr 17;8(17):15217-15228. doi: 10.1021/acsomega.3c00210. eCollection 2023 May 2.
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 CD4CD25Foxp3Treg 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.
炎症性肠病（IBD）包括克罗恩病和溃疡性结肠炎，其病因复杂，可能由代谢失调引起。先前的代谢组学研究发现壬二酸（AzA）水平降低与IBD之间存在关联。在此，代谢组学工作台的数据显示，IBD患者（PR000639）和硫酸葡聚糖钠（DSS）诱导的小鼠（PR000837）中AzA的含量降低。然后使用DSS诱导的小鼠模型研究了AzA对IBD的影响，结果表明AzA减轻了临床活动，减少了促炎细胞因子的产生，并降低了肠系膜淋巴结中CD4CD25Foxp3调节性T细胞的百分比。通过网络药理学分析，我们发现了99个可能受AzA调控的IBD相关候选基因。对候选基因进行富集分析后，肾素-血管紧张素系统（RAS）通路是富集程度最高的通路之一。此外，AzA逆转了DSS诱导后RAS重要成分（ACE、ACE2和MAS1L）表达的增加，表明AzA可能通过RAS通路发挥治疗作用。本研究表明，AzA可能是一种有前途的IBD治疗药物。
