Artesunate ameliorates experimental colitis by suppressing intestinal inflammation and modulating the gut microbiota

Artesunate (ART) is a semi-synthetic derivative of artemisinin with well-established antimalarial activity. In this study, we demonstrate that ART treatment markedly attenuates disease severity in dextran sulfate sodium (DSS)-induced colitis. ART significantly reduces the accumulation of inflammatory neutrophils, monocytes, Th17 cells, and IL-17-producing ILCs and γδT cells in the colon, accompanied by suppression of pro-inflammatory gene expression, including Tnf, Il6, and Il1b, and upregulation of anti-inflammatory mediators such as Tgfb and Il10. In parallel, ART restores the expression of intestinal tight junction proteins ZO-1 and claudin-1, indicating improved epithelial barrier integrity. ART treatment inhibits the IL-17 production from both Th17 cells and other lymphocytes. ART also reshapes the gut microbiota, which contributes to protection against DSS-induced colitis. Notably, mesalazine co-treatment with ART augmented its protective efficacy against DSS-induced colitis. Collectively, these findings identify ART as a potent modulator of intestinal inflammation and barrier function, highlighting its therapeutic potential for mucosal inflammatory diseases.