Grape seed proanthocyanidin rescues rats from steatosis: a comparative and combination study with metformin.

Nonalcoholic fatty liver disease (NAFLD), a premorbid condition, lacks proper management owing to multitude of abnormalities. In this study, we compared the effects of a potent antioxidant, grape seed proanthocyanidins (GSP), and an insulin sensitizer, metformin (MET), in high-fat-fructose-diet- (HFFD-) induced albino Wistar rat model of NAFLD. Either GSP (100 mg/Kg b.w) or MET (50 mg/Kg b.w) or both were administered as therapeutic options. HFFD-fed rats showed abnormal plasma lipid profile, inflammation, and steatosis of the liver when examined by biochemical and histology techniques. Increased lipid storage, lipogenesis, and reduced lipolysis were evident from mRNA expression studies of hepatic lipid droplets (LD) proteins, sterol regulatory element binding 1c (SREBP 1c), and peroxisome proliferator activated receptor- α (PPAR- α ). GSP administration to HFFD-fed rats caused 69% reduction in hepatic TG levels, whereas MET caused only 23%. The combination treatment reduced TG levels by 63%. GSP reduced the mRNA expression of SREBP1c and LD proteins and increased that of PPAR- α more effectively compared to MET in HFFD-induced hyperlipidemic rats. Combination of MET and GSP improved the metabolism of lipids effectively, but the effect was not additive in restoring lipid levels.