Abstract
Angelica sinensis polysaccharide (ASP) has hepatoprotective effects in liver injury models. However, its role and mechanism in chronic liver fibrosis have not been fully elucidated. In this study, a carbon tetrachloride (CCl4)-induced chronic liver fibrosis mouse model was established. The results showed that ASP treatment reduced serum alanine aminotransferase by approximately 50% and liver fibrosis areas by approximately 70%. Hepatic stellate cell (HSC) activation was inhibited in ASP-treated mice. Furthermore, the mechanism was studied in-depth, focusing on the interleukin 22/signal transducer and activator of transcription 3 (IL-22/STAT3) axis. Concentrations of 50 μg/ml and 100 μg/ml ASP induced the secretion of IL-22 in vitro, which further increased at a concentration of 200 μg/ml. Moreover, in vivo data showed that ASP significantly promoted IL-22 production in splenocytes and liver tissues. The antifibrotic effects of ASP were abolished after IL-22 neutralization. In addition, ASP activated the STAT3 pathway in the liver, as demonstrated by a 2-fold increase compared to that of the CCl4 group, which was abrogated by the IL-22 antibody. Subsequently, we showed that the antifibrotic effects of ASP were abrogated by blocking STAT3 with S3I-201. In conclusion, ASP effectively alleviates chronic liver fibrosis by inhibiting HSC activation through the IL-22/STAT3 pathway.