Vinpocetine Attenuates Hepatic Steatosis by Modulating Key Lipogenic and Lipid Transport Genes (PPAR‐ γ, SREBP, and FAT/CD36) in Experimental Non‐Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder characterized by excessive lipid accumulation in hepatocytes and is strongly associated with obesity, insulin resistance, and dyslipidaemia. Targeting key regulators of hepatic lipid metabolism represents an important therapeutic strategy. Vinpocetine, a phosphodiesterase-1 inhibitor, exhibits metabolic and anti-inflammatory properties, but its role in hepatic lipid homeostasis remains insufficiently defined. To evaluate the effect of vinpocetine on hepatic steatosis and its regulatory impact on key lipid-metabolism genes, including peroxisome proliferator-activated receptor-α (PPAR-α), PPAR-γ, sterol regulatory element-binding protein-1c (SREBP-1c), and fatty acid translocase/cluster of differentiation 36 (FAT/CD36), in an experimental NAFLD model. NAFLD was induced in rats using a high-fat diet. Animals received vinpocetine (10 mg/kg, i.p.) daily for 5 weeks. Hepatic lipid accumulation was assessed histologically and biochemically, while gene expression of PPAR-α, PPAR-γ, SREBP-1c, and FAT/CD36 was analyzed using RT-PCR. Vinpocetine significantly reduced hepatic lipid accumulation compared with untreated NAFLD controls. It upregulated PPAR-α expression while downregulating PPAR-γ, SREBP-1c, and FAT/CD36, indicating enhanced fatty-acid oxidation and reduced lipogenesis and lipid influx. Treatment also improved lipid profile parameters (reduced TC, TG, LDL, and restored HDL), lowered liver enzyme levels, increased antioxidant activity (elevated glutathione), and reduced oxidative and nitrosative stress (decreased malondialdehyde and nitric oxide), accompanied by improved liver histology. Vinpocetine attenuates hepatic steatosis in NAFLD by modulating genes involved in lipid metabolism, suggesting potential therapeutic value. Further studies are required to confirm these findings and clarify mechanisms.