Inhibition of Lipid Accumulation in NAFLD Liver by Extract of Rosa laevigata Fruit Extract through Activation of the PI3K-AKT Signaling Pathway

Non-Alcoholic Fatty Liver Disease (NAFLD) is a chronic metabolic disorder primarily characterized by lipid accumulation in the liver, which is its main pathological feature. The fruit of Rosa laevigata Michx (RLF) is recognized for its diverse bioactive properties and has garnered significant attention for its potential use in developing dietary supplements for NAFLD treatment. However, its lipid-lowering efficacy and underlying mechanisms remain unclear. To investigate this, we developed an NAFLD cell model by treating HepG2 cells with oleic acid and evaluated the lipid-lowering effects of RLF extract. The effectiveness was measured using five indicators: triglycerides (TG), total cholesterol (T-CHO), low-density lipoprotein cholesterol (LDL-C), aspartate transaminase (AST), and alanine transaminase (ALT). The lipid-lowering mechanism was predicted using HPLC-MS alongside network pharmacology. Antioxidant ability was evaluated using DPPH and ABTS assays, with three indicators—total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and malondialdehyde (MDA)—used to assess antioxidant effects. Additionally, Western blotting (WB) was employed to validate the network pharmacology predictions. Results indicated that, compared to the model group, the RLF extract significantly reduced TG, T-CHO, LDL, AST, and ALT levels by 55.9%, 37.1%, 25.3%, 67.5%, and 51.1%, respectively. T-AOC and SOD levels were significantly increased by 182.5% and 136.8%, respectively, while MDA content was reduced by 47.3%. WB analysis indicated that the RLF extract alleviated abnormalities in lipid metabolism and antioxidant-related genes PI3K and p-AKT. These findings suggest that the therapeutic effects of RLF extract on NAFLD may be mediated by the modulation of oxidative damage responses via the PI3K-AKT signaling pathway.