Abstract
OBJECTIVE: To observe the therapeutic effect of Zaozhu Yinchen Decoction (ZZYC) on rats with non-alcoholic steatohepatitis (NASH) and explore its mechanism of action related to myeloid-derived suppressor cells (MDSCs). METHODS: A NASH rat model was established by feeding a high-fat diet for 16 weeks, and drug intervention was initiated from the 9th week of modeling, lasting for 8 weeks. The general status of rats was observed. Biochemical methods were used to detect the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as the triglyceride (TG) content in liver tissue. Hematoxylin-eosin (HE) staining and Oil Red O staining were performed to observe the pathological changes of liver tissue. Flow cytometry was used to detect the expression level of MDSCs in peripheral blood. Enzyme-linked immunosorbent assay (ELISA) was employed to determine the protein expression levels of arginase 1 (ARG-1) and the pro-inflammatory factor S100 calcium-binding protein A9 (S100A9) in liver tissue. RESULTS: Compared with the normal group, rats in the model group exhibited typical histological features of NASH. After treatment with ZZYC decoction, hepatocellular steatosis and inflammatory infiltration were significantly alleviated. Compared with the normal group, the model group showed a significant increase in liver weight, serum ALT and AST activities, liver TG and free fatty acid (FFA) content, peripheral blood MDSC level, and the expression of ARG-1 and S100A9 in liver tissue (all P<0.01). These indicators were significantly reduced after ZZYC decoction treatment (all P<0.05). CONCLUSION: ZZYC decoction exerts a significant pharmacological effect on improving hepatocellular steatosis, ballooning degeneration, and inflammation in NASH rats. Meanwhile, it can markedly reduce the level of peripheral blood MDSCs and the expression of ARG-1 and S100A9 in liver tissue. These findings suggest that the therapeutic mechanism of ZZYC decoction for NASH is closely associated with the regulation of MDSCs.