Tauroursodeoxycholic acid liposome alleviates DSS-induced ulcerative colitis through restoring intestinal barrier and gut microbiota

Abstract

Ulcerative colitis (UC) is a chronic and progressive inflammatory disease that damages the colonic mucosa and disrupts the intestinal epithelial barrier. The current clinical treatment for UC is mainly chemotherapy, which has the limited effectiveness and severe side effects. It mainly focuses on the treatment of inflammation while neglecting the repair of the intestinal mucosa and the restoration of the microbiota balance. Here, we aimed to address these challenges by using an amphipathic bile acid -tauroursodeoxycholic acid (TUDCA) to replace cholesterol (CHL) in conventional liposomes. We prepared TUDCA/Emodin liposomes by incorporating the hydrophobic drug emodin. The experimental results indicated that TUDCA/Emodin Lip had uniform particle size distribution, good stability, low cytotoxicity, and exhibited good mucus permeability and anti-inflammatory activity in in vitro experiments, and was able to protect cells from oxidative stress. After oral administration, TUDCA/Emodin Lip significantly alleviated the severity of UC. This was evidenced by increased colon length, decreased inflammation and reduced colonic endoplasmic reticulum stress (ERS). Furthermore, TUDCA/Emodin Lip maintained the normal levels of the tight junction proteins Claudin-1 and ZO-1, thereby restoring the integrity of the intestinal barrier. Importantly, TUDCA/Emodin Lip also promoted the ecological restoration of the gut microbiota, increased overall abundance and diversity. Taken together, TUDCA/Emodin Lip can fundamentally restore intestinal homeostasis, this work provides a new, efficient and easily transformable treatment for UC.