Dihydromyricetin Improves Ulcerative Colitis by Suppressing NLRP3 Inflammasome Activation Caused by Dysbiosis of Gut Microbiota.

Purpose: Dihydromyricetin (DMY) is known for its wide range of pharmacological effects and has been approved as a dietary supplement. This study aimed to investigate the therapeutic effects of DMY on dextran sulfate sodium (DSS)-induced disruption of intestinal homeostasis in mice and to explore the underlying molecular mechanisms. Methods: To establish a model of colitis, mice were treated with a 3% DSS solution, followed by gavage administration of DMY for therapeutic intervention. Techniques such as histomorphology, RT-qPCR, 16S rRNA sequencing, and Western blot analysis were used. Results: DMY alleviated several physiological symptoms in colitis mice, including a reduction in the disease activity index (DAI) and spleen index, as well as decreases in the numbers of white blood cells, lymphocytes, and monocytes. Additionally, DMY helped repair the intestinal mucosal barrier function, reshaped the composition of gut microbiota, and regulated intestinal immune responses. These effects collectively contributed to the partial restoration of intestinal homeostasis in colitis mice. Furthermore, experiments with NLRP3-/- mice and pseudo-germ-free mice confirmed that DMY exerts its anti-colitis effects through the gut microbiota-NLRP3 inflammasome axis. Conclusion: DMY helps regulate intestinal homeostasis in colitis mice by suppressing the NLRP3 inflammasome via the gut microbiota. Our study provides new evidence supporting DMY as a potential therapeutic agent for colitis.