<b>Oleanolic acid </b><b>alleviate intestinal inflammation</b><b> by inhibiting </b><b>Takeda G-coupled protein receptor (TGR) 5 mediated Cell</b><b> </b><b>A</b><b>poptosis</b>

Oleanolic acid (OA) is a bioactive compound present in plant-based foods known for its benificial impact on gastrointestinal health, specifically in alleviating diarrhea. Nonetheless, the underlying mechanisms by which OA mitigates gut epithelial damage have yet to be elucidated. In this study, OA significantly markedly amerliorated adverse effects induced by Dextran Sulfate Sodium (DSS), including weight loss, splenic hypertrophy, reductions in the size and mass of the small intestine and colon, along with impaired diminished intestinal weight, epithelial morphological damage, and intestinal organoid formation (P&lt;0.05) in a murine model. Remarkably, compared to normal mice, standalone administration of OA had no discernible impact on the animals. Concurrently, we identified a significant up-regulation in the expression levels of TGR5, TNF-α, and BAX in the intestines of DSS-exposed mice, coupled with a decline in Bcl2 expression. Oral administration of OA efficaciously counteracted these alterations (P&lt;0.05).Correlation analyses revealed a robust association between TGR5 and BAX expression (R=0.60). Minimal changes were observed in bile acid composition and gut microbiota. To probe the role of TGR5 in cellular apoptosis, further, a lentivirus transfection approach was utilized to induce TGR5 overexpression in intestinal epithelial cells (IPEC-J2). RNA sequencing indicated that TGR5 overexpression significantly influenced biological processes, particularly in modulating cellular activation and intercellular adhesion, in contrast to the control group cells. Functional assays, namely CCK-8, EdU, and IP staining, substantiated that TGR5 overexpression compromised cell viability and accelerated apoptosis. Additionally, TGR5 overexpression led to a pronounced downregulation of PCNA, Claudin-1, and Bcl2. Notably, OA treatment in TGR5-overexpressed cells restored cell viability, suppressed TGR5 and BAX expression, and augmented Bcl2 expression. In sum, our data suggest that OA mitigates intestinal epithelial apoptosis and bolsters cellular proliferation by downregulating TGR5. This research provides valuable insights into the prospective utility of OA as a functional food supplement or adjunctive therapeutic agent for enhancing gastrointestinal health.