Betulinic Acid–Mediated NR1D1 Alleviates Dextran Sulfate Sodium–Induced Colitis in Mice by Modulating VDAC1/NF‐κВ

Purpose: Inflammatory bowel disease (IBD) can severely disrupt intestinal health, leading to chronic inflammation. Betulinic acid (BHA) has demonstrated anti‐inflammatory and antioxidant properties. This study aims to explore the mechanism by which BHA alleviates colitis through the regulation of the key circadian gene REV‐ERBα (NR1D1) in a DSS‐induced colitis mouse model. Methods: The study first utilized in vivo experiments to establish a mouse model of colitis induced by DSS, investigating the effect of BHA in alleviating colitis through the regulation of NR1D1. Subsequently, an inflammatory model was established at the cellular level using CCD841 cells treated with 100 ng/mL LPS to explore the regulatory mechanism of BHA on colitis. Results: Our results indicate that oral administration of BHA effectively alleviates colitis symptoms, as shown by reduced disease activity index and histopathological scores. Notably, we found that BHA improves intestinal inflammation in DSS‐induced mice by downregulating VDAC1/NF‐κB. In addition, in vitro experiments demonstrate that the anti‐inflammatory effects of BHA are closely related to the NR1D1 gene. Conclusion: Our findings demonstrate the potential of BHA as a preventive and therapeutic agent for IBD.