CYCLOASTRAGENOL SUPPRESSES HEPATIC STELLATE CELL ACTIVATION TO ALLEVIATE LIVER FIBROSIS THROUGH THE PI3K/AKT/MTOR SIGNALING PATH WAY AND AUTOPHAGY

Liver fibrosis is a pathological process of various liver diseases, and a large number of studies have shown that liver fibrosis is reversible. Natural products are important sources of drugs for treating liver fibrosis. The present study evaluated the protective effect of cycloastragenol (CAG) on liver fibrosis and the underlying mechanisms.The mouse model of liver fibrosis was established by intraperitoneal injection of carbon tetrachloride (CCl4) and olive oil. Subsequently, CAG was administered orally at different doses (2.5 mg/kg/d, 5 mg/kg/d, 10 mg/kg/d), and the degree of liver fibrosis was assessed using hematoxylin-eosin, Van Gieson, and Sirius Red staining. Alanine aminotransferase, aspartate aminotransferase, hyaluronic acid, and hydroxyproline levels were detected using biochemical analyses. The mRNA and protein expression levels of alpha-SMA, LC3, P62, PI3K, Akt, and mTOR in the liver tissue were assessed by reverse-transcription polymerase chain reaction and western blot, respectively. The expression of fibrogenesis-related marker alpha-SMA in the liver tissue was assessed using immunofluorescence. As expected, CAG alleviated liver fibrosis and suppressed hepatic stellate cell activation. And then, CAG inhibited autophagy and activated the PI3K/Akt/mTOR signaling pathway. Thus, CAG attenuated CCI4-induced liver fibrosis in mice by inhibiting autophagy and activating the PI3K/Akt/mTOR signaling pathway.