Protective Effects of Aucubin in DSS-Induced Colitis: Modulation of Inflammatory Pathways, Intestinal Barrier Integrity, and Gut Microbiota

As an active ingredient in Eucommia leaf, aucubin (AU) is natural and safe, and studies have shown that aucubin (AU) demonstrates great potential in its anti-inflammatory, antioxidant, neuroprotective, and anti-osteoporotic properties. However, AU has been less studied in colitis. In this experiment, we used DSS-induced mice to establish a colitis model to investigate the ability of AU to alleviate colitis. The results show that, in animal experiments, AU increased body weight, reduced disease activity index (DAI) scores and organ indices, restored colon morphology, and increased superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and catalase (CAT) levels in mouse serum and colon. It also reduced malondialdehyde (MDA) levels, decreased the relative mRNA expression levels of inflammatory factors <i>IL-1β</i>, <i>TNF-α</i>, <i>IL-18</i>, <i>MyD88</i>, and <i>NF-κB</i>, and increased the relative mRNA expression levels of intestinal barrier-related genes <i>OCLN</i>, <i>CLDN1</i>, <i>CLDN2</i>, <i>ZO-2</i>, and <i>MUC1</i>. AU also upregulated the abundance of bacterial groups such as <i>Bacteroidota</i>, <i>Firmicutes</i>, and <i>Verrucomicrobiota</i>, and downregulated the abundance of bacterial groups such as <i>Proteobacteria</i> and <i>Deferribacterota</i>, thereby regulating the intestinal microbiota. In cell experiments, AU increased the relative mRNA expression levels of intestinal barrier-related genes <i>MUC2</i>, <i>ZO-1</i>, <i>OCLN</i>, and <i>CLDN1</i>, reduced the relative expression levels of inflammatory factors <i>IL-1β</i> and <i>TNF-α</i>, and increased the relative expression level of the anti-inflammatory factor <i>IL-10</i>. Additionally, AU significantly reduced the relative expression levels of <i>IL-1β</i>, <i>IL-1R</i>, <i>MyD88</i>, <i>TAK1</i>, <i>IKKα</i>, and <i>RelA</i>. This study provides a theoretical and technical basis for the large-scale preparation of aucubin and the alleviation of inflammatory bowel disease.