82. Bifendate treatment attenuates hepatic
steatosis in cholesterol/bile salt- and high-fat diet-induced hypercholesterolemia
in mice
Si-Yuan Pana,
, Rong Yanga,
Hang Donga,
Zhi-ling Yub
and Kam-Ming Koc
aDepartment of
Pharmacology, Beijing University of Chinese Medicine, Beijing, China bSchool
of Chinese Medicine Hong Kong Baptist University, Kowloon Tong, Hong Kong,
China cDepartment of Biochemistry, Hong Kong University of Science
and Technology, Clear Water Bay, Hong Kong, China
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 to108%), 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.
Keywords: Bifendate;
Fenofibrate; Hypercholesterolemia; Fatty liver; Triglyceride; Total cholesterol