Tauroursodeoxycholic acid ameliorates DSS-induced ulcerative colitis via regulating TLR4/NLRP3/pyroptosis axis and Keap1/Nrf2 pathway and restoring gut barrier function.

Abstract

Tauroursodeoxycholic acid (TUDCA) is a naturally occurring endogenous hydrophilic bile acid with therapeutic potential for ulcerative colitis (UC). However, the potential mechanism of its anti-UC effect remains unclear. Hence, this study investigated the therapeutic efficiency of TUDCA on dextran sulfate sodium (DSS)-induced colitis and elucidated the underlying mechanism. UC symptoms were analyzed, and colon tissue and serum were collected for the analysis of gut barrier function, intestinal inflammation, and oxidative stress. Results indicated that TUDCA effectively inhibited body weight loss, restored colon length, and alleviated colon injury. Mechanistically, TUDCA maintained gut barrier function by upregulating MUC2, claudin-1, ZO-1, and occludin protein expressions. TUDCA normalized inflammatory factors levels through inhibiting TLR4/NLRP3/pyroptosis axis. In addition, TUDCA restored the levels of antioxidants and oxidants through regulating Keap1/Nrf2 pathway. These findings indicate for the first time that TUDCA alleviates gut barrier dysfunction, intestinal inflammation, and oxidative stress in colitis mice through TLR4/NLRP3/pyroptosis axis and Keap1/Nrf2 pathway, and has the potential to be a promising candidate medication for UC treatment and related intestinal inflammation.