Asiaticoside alleviates inflammation and intestinal barrier dysfunction in Crohn's disease-like colitis in a manner...

Asiaticoside (AS) improves colitis by inhibiting inflammation and protecting the intestinal barrier, but its role in Crohn's disease (CD) is still unclear. In this study, the TNBS-induced mouse colitis model and TNF-α-stimulated Caco2 cell injury model were used, and AS and RhoA/ROCK pathway activator LPA were used for intervention. The inflammatory level and pathological damage were evaluated by monitoring body weight, DAI score, colon length measurement, ELISA, and pathological staining. The intestinal barrier function was detected by immunofluorescence, FD4 concentration, TEER assay, and bacterial translocation. Molecular docking and Western blot were used to explore the RhoA/ROCK/MLC pathway. AS significantly improved body weight loss, reduced DAI score, alleviated colon shortening and histopathological damage in TNBS mice, significantly reduced serum FD4 concentration, inhibited bacterial translocation to immune organs, raised colon TEER value, and promoted ZO-1 expression. Moreover, AS effectively inhibited the RhoA/ROCK/MLC axis in colon tissue, and lessened pro-inflammatory cytokine contents. Notably, LPA significantly attenuated the anti-inflammatory and intestinal barrier protective actions of AS. In the Caco2 cell model, AS also inhibited TNF-α-induced RhoA/ROCK/MLC pathway activation, reduced inflammation, reduced apoptosis, and repaired intestinal barrier integrity and function. AS improved intestinal inflammatory injury and intestinal barrier dysfunction in CD-like colitis, and these effects were associated with modulation of the RhoA/ROCK/MLC signaling pathway.