Shih-Yu Lee
National Defense Medical Center, TAIWAN
Title: 4-Acetylantoquinono B derived from Androdia cinamomea ameliorates non-alcoholic steatohepatitis by suppression of ER stress and NLRP3 inflammasome activation in vitro and in vivo
Biography
Biography: Shih-Yu Lee
Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) is 25% or above worldwide. However, the safe and effective agents for NAFLD/NASH still require further investigation. The present study aims to investigate the hepatoprotective effect and mechanism of 4-acetylantroquinonol B (4AAQB), a natural ubiquinone derivative from the mycelium of Antrodia cinnamomea, in vitro and in vivo. Raw264.7 and HepG2 cells were treated with 4AAQB and then stimulated with LPS (0.1/1.0 μg/ml) for 24h. Endoplasmic reticulum (ER) stress and NLRP3 inflammasome were analyzed by western blotting in both cell lines. In vivo model, male C57BL/6 mice were fed with methionine/choline-deficient (MCD) diet along with vehicle or 4AAQB (10 mg/kg, IP, once a day) for 10 consecutive days. The plasma levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. The liver tissues were analyzed for histology (hematoxylin and eosin stain), oxidative stress markers, and proteins levels involved in ER stress, NLRP3 inflammasome, lipogenesis, autophagy, and inflammatory markers. We found that 4AAQB significantly suppressed LPS-induced ER stress and NLRP3 inflammasome activation in both of the in vitro models. In addition, 4AAQB ameliorated MCD-induced NASH and down-regulated ER tress and NLRP3 inflammasome activation in vivo. Based on these data, 4AAQB treatment might be a tangible therapeutic strategy for NAFLD/NASH.