Schisandrin Protects against Ulcerative Colitis in Mice by Inhibiting the SGK1/NLRP3 Pathway and Restores Gut Microbiota Balance

The fruit of Schisandra chinensis (Turcz.) Baill. (SC) is an important traditional Chinese medicine, and it has been used for treating diarrhea and recorded in the Chinese Pharmacopoeia. However, the effect of Schisandrin (SCH, quality marker of SC) on ulcerative colitis has rarely been reported. This study aimed to explore the possible mechanism of action of SCH in the treatment of ulcerative colitis (UC) by regulating NLRP3 and affecting the gut microbiota (GM). As compared to the model group, the mice in SCH had significantly slower weight loss, effectively alleviated the degree of colitis, and decreased levels of the inflammatory factors TNF-alpha, IL-1beta, IL-18, IL-6, and other related proteins (NLRP3, Caspase-1, SGK1). SCH can improve intestinal barrier function and has a good protective effect on goblet cells. In addition, the results of the analysis of GM and BAs showed that SCH significantly improved the imbalance in GM induced by DSS in mice by increasing the relative abundance of lactobacilli, reducing the relative number of Bacteroides, and promoting the conversion of primary BAs to secondary BAs, which helps maintain intestinal homeostasis. These results show that schisandrin can restore colon morphology, attenuate the weight loss, increase DAI score and repair intestinal barrier damage in mice with colitis, and its mechanism is closely related to the regulation of the SGK1/NLRP3 pathway and restoration of gut microbiota (GM) balance, indicating that Schisandrin could be used as a potential drug for treating.