Ursolic Acid Alleviates DSS-Induced Colitis and Associated Liver Damage by Restoring Treg/Th17 Balance and Modulating Gut Microbiota and Its Histidine Metabolism

作者：Man Zhao, Mengqi Liu, Fengyang Wu, Chong Li, Shudong Liu, Xinyu Yang, Zhonghua Wei, Baojiang Chen, Shuaijuan Han · 发表于：Journal of Agricultural and Food Chemistry · 年份：2025 · DOI：10.1021/acs.jafc.5c00220 · 被引用次数：7 · 研究领域：Inflammatory Bowel Disease、Pharmacological Effects of Natural Compounds、Liver Disease Diagnosis and Treatment

Ursolic acid (UA), a natural compound abundant in fruits and vegetables, exhibits established anti-inflammatory and hepatoprotective properties. This study investigated the therapeutic potential of UA as a dietary supplement for DSS-induced colitis and secondary liver injury using both an in vivo DSS-induced colitis mouse model and an in vitro intestinal epithelial cell model. Colitis model mice were administered UA at doses of 5, 25, 100, and 250 mg/kg. Through comprehensive analyses, including enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), immunofluorescence (IF), Western blot, 16S rRNA sequencing, untargeted metabolomics, and transcriptomics, we demonstrated that 25 mg/kg UA optimally alleviated colitis symptoms. The mechanism involves restoring the balance between T regulatory cells (Treg) and T helper 17 cells (Th17) to reduce inflammation, potentially mediated by increased production of propionate from short-chain fatty acid (SCFA)-producing bacteria. Additionally, UA inhibits Escherichia coli ( E. coli ) growth through the action of the microbial metabolite l -histidine, thereby enhancing intestinal barrier integrity and inhibiting pyroptosis. Moreover, 25 mg/kg of UA exerts protective effects against liver injury by suppressing inflammation-related signaling pathways in colitis mice. These findings position UA as a promising functional food component for managing colitis and its hepatic complications.