Astragaloside IV Alleviates Acute Liver Failure Induced by D-GalN/LPS by Upregulating Autophagy and Reducing Inflammation

Abstract

Abstract Acute liver failure (ALF) is a life-threatening condition that manifests in an extremely serious manner and progresses rapidly. The following study investigated the protective effect of astragaloside IV (AS-IV), a traditional Chinese drug, on ALF, and its underlying mechanisms, focusing on autophagy and inflammation regulation. Mice were randomly divided into a saline group, a D-galactosamine and lipopolysaccharide (D-GalN/LPS) group and an AS-IV group. Biochemical analysis, immunohistochemistry, cytometric bead array, high-throughput quantitative PCR, flow cytometry and Western analysis were used to assess inflammation and liver damage 5 hours after D-GalN/LPS exposure. AS-IV treatment reduced mortality by alleviating D-GalN/LPS-induced hepatic damage and decreasing inflammation (decreasing Ly6c+ monocyte levels, reducing inflammatory cytokines and increasing anti-inflammatory factors) as well as upregulating autophagy. Furthermore, PCR array was employed to detect expression of autophagy-related genes, which demonstrated a Log2 fold change in gene expression between the AS-IV and D-GalN/LPS groups ranging from 1.19 to -3.53, with Tnfsf10 showing the largest alteration between the two groups. These data suggest that AS-IV may alleviate ALF by upregulating autophagy and reducing inflammation, and it may therefore be an interesting drug for aleviating ALF.