Li Rong, Huang Xue, Yang Lu, Liang Xiao, Huang Wenjun, Lai Keng Po, Zhou Liming
Laboratory of Environmental Pollution and Integrative Omics, Guilin Medical University, Guilin, China.
Department of Gastroenterology, Guigang City People's Hospital, The Eighth Affiliated Hospital of Guangxi Medical University, Guigang, China.
Front Nutr. 2022 May 19;9:867692. doi: 10.3389/fnut.2022.867692. eCollection 2022.
Ulcerative colitis (UC) is an inflammatory bowel disease that causes inflammation and ulcers in the digestive tract. Approximately 3 million US adults suffer from this disease. Mesalazine, an anti-inflammatory agent, is commonly used for the treatment of UC. However, some studies have demonstrated side effects of mesalazine, such as acute pancreatitis and hypereosinophilia. Therefore, a better understanding of the anti-inflammatory mechanism of mesalazine in UC could help improve the effectiveness of the drug and reduce its side effects. In this study, we used a dextran sodium sulfate-induced UC mouse model, and applied network pharmacology and omics bioinformatics approaches to uncover the potential pharmaceutical targets and the anti-inflammatory mechanism of mesalazine.
Network pharmacology analysis identified the core targets of mesalazine, biological processes, and cell signaling related to immunity and inflammatory responses mediated by mesalazine. Molecular docking analysis then indicated possible binding motifs on the core targets (including TNF-α, PTGS2, IL-1β, and EGFR). Metabolomics and 16S metagenomic analyses highlighted the correlation between gut microbiota and metabolite changes caused by mesalazine in the UC model.
Collectively, the omics and bioinformatics approaches and the experimental data unveiled the detailed molecular mechanisms of mesalazine in UC treatment, functional regulation of the gut immune system, and reduction of intestinal inflammation. More importantly, the identified core targets could be targeted for the treatment of UC.
溃疡性结肠炎（UC）是一种炎症性肠病，可导致消化道炎症和溃疡。美国约有300万成年人患有这种疾病。美沙拉嗪是一种抗炎药，常用于治疗UC。然而，一些研究已经证明了美沙拉嗪的副作用，如急性胰腺炎和嗜酸性粒细胞增多。因此，更好地了解美沙拉嗪在UC中的抗炎机制有助于提高药物疗效并减少其副作用。在本研究中，我们使用葡聚糖硫酸钠诱导的UC小鼠模型，并应用网络药理学和组学生物信息学方法来揭示美沙拉嗪的潜在药物靶点和抗炎机制。
网络药理学分析确定了美沙拉嗪的核心靶点、生物学过程以及与美沙拉嗪介导的免疫和炎症反应相关的细胞信号传导。分子对接分析随后表明了核心靶点（包括TNF-α、PTGS2、IL-1β和EGFR）上可能的结合基序。代谢组学和16S宏基因组分析突出了UC模型中美沙拉嗪引起的肠道微生物群与代谢物变化之间的相关性。
总体而言，组学和生物信息学方法以及实验数据揭示了美沙拉嗪在UC治疗中的详细分子机制、肠道免疫系统的功能调节以及肠道炎症的减轻。更重要的是，所确定的核心靶点可作为UC治疗的靶点。
