Nonalcoholic fatty liver disease (NAFLD) is considered to be a hepatic manifestation of metabolic syndrome, and its incidence is rapidly increasing. However, there is a lack of appropriate drugs for the therapy of NAFLD. In the present article, we aimed to elucidate the protective effects and mechanisms of Akebia saponin D (ASD) against NAFLD on ob/ob mice and BRL cells. ASD significantly decreased hepatic steatosis and heptocyte apoptosis in ob/ob mice. Furthermore, ASD significantly activated the autophagic flux assessed by decreased the expression of LC3-II, p62 accumulation of autophagosomes. In BRL cells, ASD prevented OA induced lipid droplets and increase the autophagic flux acting as increase the number of autolysosomes than autophagosomes in mTagRFP-mWasabi-LC3. ASD treatment also prevented OA induced LC3-II, p62, Beclin and phospho-mTOR expression. These effects were similar to the effects cotreatment with rapamycin. ASD treatment could not prevent the OA increased autophagy related protein expression after treated with CQ or siRNA-mediated knockdown of Atg7. These results suggest that Akebia saponin D alleviates hepatic steatosis targeted at the fusion of autophagosomes to lysosomes, autophagy modulation via ASD may offer a new strategy for treating NAFLD.
- The American Society for Pharmacology and Experimental Therapeutics