Trilobatin ameliorates ulcerative colitis by reducing inflammation and enhancing intestinal barrier function via regulating HMGB1-mediated TLR4/NF-κB signaling pathway.

Abstract

Ulcerative colitis (UC) stands as the predominant chronic inflammatory immune bowel disease. This research aimed to elucidate the mechanism of Trilobatin (TLB) in dextran sodium sulfate (DSS)-induced UC, utilizing DSS-induced mice and NCM460 cells as UC models. The findings of the study confirmed that TLB could ameliorate intestinal structural damage in DSS-treated mice. TLB treatment intensified ZO-1, Occludin, and Claudin-1 levels, as well as Bcl-2, and lessened the levels of Bax in DSS-treated mice. Moreover, TLB administration enhanced the activity of SOD and reduced the content of MDA, alongside decreased levels of IL-6, TNF-α, and IL-1β. In NCM460 cells, TLB promoted cell viability and suppressed apoptosis, oxidative stress, and inflammation triggered by DSS. Moreover, levels of tight junction proteins were elevated in DSS-triggered NCM460 cells following treatment with TLB. Further, TLB was found to suppress TLR4/NF-κB signaling in DSS-elicited NCM460 cells via regulating HMGB1. In conclusion, TLB exerted its protective function in DSS-induced colitis by inactivating HMGB1-mediated TLR4/NF-κB signaling, which might provide novel strategies for therapeutic intervention in UC.