Oligomeric proanthocyanidins mitigate cholesterol and cholic acid diet-induced hepatic dysfunction in male Sprague Dawley rats

Dysregulated synthesis of hepatic cholesterol is a critical determinant of atherosclerosis. The combination of cholesterol and cholic acid (CC) diet supplementation to animal models is associated with hepatic dysfunction-mediated atherosclerosis. The current study was designed to investigate the hepatic cholesterol-lowering effects of oligomeric proanthocyanidins (OPC) in CC diet fed rats. CC diet-induced group exhibited significant increase in the hepatic lipid profile, activities of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGR), PON-1, LCAT, LPL, and LPO levels, and messenger RNA expression of HMGR, low-density lipoprotein receptor (LDLr), and HNF-4 alpha. Administration of OPC (100 mg/kg/bwt) resulted in the significant reduction of lipid profile and HMGR levels, with concomitant increase in the levels of cholesterol-regulating enzymes and upregulated expression of LDLr and HNF-4 alpha, which was similar to atorvastatin. Molecular docking studies also revealed that proanthocyanidins had a strong binding affinity to HMGR, similar to atorvastatin. Our findings suggest that OPC regulate the impaired cholesterol metabolism-associated atherosclerosis through hepatic cholesterol-lowering effect.