Bifendate treatment attenuates hepatic steatosis in cholesterol/bile salt- and high-fat diet-induced hypercholesterolemia in mice.

Effects of bifendate, a synthetic intermediate of schisandrin C (a dibenzocyclooctadiene derivative), on liver lipid contents were investigated in experimentally-induced hypercholesterolemia in mice. Hypercholesterolemia was induced by either chronic administration of cholesterol/bile salt or feeding a high-fat diet containing cholesterol and/or bile salt. Hepatic and serum total cholesterol levels were significantly increased (42-268% and 23-124%, respectively) in cholesterol or high-fat diet-treated mice, when compared with control animals receiving vehicle or normal diet. Hepatic triglyceride level was increased (up to 108%), but serum triglyceride level was significantly reduced by 23-63% in hypercholesterolemic mice. Daily administration of bifendate (0.03-1.0 g/kg, i.g.) for 4 days decreased hepatic levels of total cholesterol (9-37%) and triglyceride (10-37%) in hypercholesterolemic mice. Supplementing the high-fat diet with bifendate (0.25%, w/w) caused decreases in hepatic total cholesterol (25-56%) and triglyceride (22-44%) levels following 7 or 14 days of experiment, respectively, when compared with animals fed with high-fat diet not supplemented with bifendate. While fenofibrate treatment decreased both hepatic and serum lipid levels in hypercholesterolemic mice, bifendate treatment did not reduce serum lipid levels. Bifendate and fenofibrate caused an increase (10-41% and 59-98%, respectively) in hepatic index of hypercholesterolemic mice. The results indicate that bifendate treatment can invariably decrease hepatic (but not serum) lipid levels in various mouse models of hypercholesterolemia.