Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disorder associated with features of metabolic syndrome and oxidative stress. We examined the mechanism by which the combined extracts of Rhus verniciflua and Eucommia ulmoides extracts (ILF-RE) regulate hepatic dyslipidemia in an established NAFLD model, high-fat diet (HFD)-induced lipid dysmetabolism in rats. ILF-RE attenuated alanine aminotransferase (ALT) by 1.5% (p<0.05), aspartate aminotransferase (AST) by 1.5% (p<0.05), triglycerides by 1.5% (p<0.05), cholesterol by 2.0% (p<0.05), and lipid peroxidation by 1.5% (p<0.05) in the NAFLD model. ILF-RE, recently shown to have anti-oxidant properties, also inhibited hepatic ROS accumulation by 1.68% (p<0.05) and regulated ER-redox imbalance, a key phenomenon of ER stress. Due to nutrient overload stress-associated protein folding, ER stress and downstream SREBP-lipogenic transcription signaling were highly activated, and the mTORC1-AMPK axis was also disturbed, leading to hepatic steatosis. ILF-RE results in recovery from hepatic conditions induced by nutrient-based protein folding stress signaling and the ER stress-SREBP and AMPK-mTORC1-SREBP1 axes. Based on these results, ILF-RE is suggested to be a potential therapeutic strategy for hepatic steatosis and may represent a promising novel agent for the prevention and treatment of NAFLD.
