Non-alcoholic fatty liver disease (NAFLD) is a clinical pathological syndrome of hepatic parenchymal cell steatosis caused by excessive lipid deposition, which is the chronic liver disease with the highest incidence in China. Asperuloside (ASP), a kind of iridoid compound, possesses natural pharmacological effects of anti-tumor, anti-inflammatory, antioxidant and anti-obesity. However, whether ASP can improve NAFLD remains unclear.We aimed to investigate the effect of ASP on NAFLD mice induced by high-fat diet (HFD), and explore its mechanism in vivo and in vitro.Pharmacodynamics of ASP was studied by HFD induction in NAFLD mice. HepG2 cells were induced by palmitic acid (PA) as cell model to investigate the effect of ASP on lipid deposition and inflammatory infiltration. Expression of Adenosine monophosphate - activated protein kinase (AMPK) signaling pathway and NOD-like receptor pyrin containing 3 (NLRP3) inflammasome were detected by Western blot and RT-PCR. Cytokines IL-1β and TNF-α were detected by ELISA.ASP alleviated liver injury and inflammatory damage in mice with NAFLD. In addition, ASP improved lipid deposition as well as inflammatory response in HFD-induced NAFLD mice and PA-stimulated HepG2 cells. ASP ameliorated lipid deposition and inflammatory response by regulating the p-AMPK/SREBP-1c signaling pathway and NLRP3 inflammasome.Our results suggest that ASP improve lipid deposition and inflammatory infiltration in NAFLD mice via regulating the AMPK/SREBP-1c signaling pathway and NLRP3 inflammasome, which may be an effective candidate for the treatment of NAFLD.Copyright © 2023 Elsevier B.V. All rights reserved.