Artemisitene ameliorates carbon tetrachloride-induced liver fibrosis by inhibiting NLRP3 inflammasome activation and modulating immune responses.

Artemisitene (ATT), an artemisinin (ART) analog retaining the endoperoxide moiety and incorporating an additional α, β-unsaturated carbonyl structure, exhibits enhanced biological activities. However, its therapeutic effects on liver fibrosis remain unclear. In this study, we demonstrated that ATT significantly alleviated liver inflammation and fibrosis induced by carbon tetrachloride (CCL) in mice. ATT treatment markedly reduced the count of neutrophils in the liver, as well as macrophages in both the liver and spleen. Additionally, the frequencies of Th2 and Th17 cells were significantly lowered, while Th1 cells frequency and the Th1/Th2 index were notably increased. The frequency of ILC2 cells, correlated with ST2 and IL-33 expression levels, was also significantly lowered. Consistently, ATT inhibited NLRP3 inflammasome activation, which was positively associated with AST and ALT levels, and with the count of Neutrophils, macrophages, and ILC2 cells, but negatively correlated with Th1frequeny. Furthermore, liver fibrosis severity showed a significant positive correlation with neutrophil and Th17 cell counts in the liver, and a negative correlation with Th1 cell count and the Th1/Th2 index. Therefore, ATT alleviated CCL-induced mice liver fibrosis through NLRP3 inflammasome inhibition and immunomodulation.