Sun N[1], Pan SY[1], Zhang Y[1], Wang XY[1], Zhu PL[1], Chu ZS[1], Yu ZL[2], Zhou SF[3], Ko KM[4]
[1] Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, China.
[2] School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
[3] Department of Pharmaceutical Sciences,College of Pharmacy, University of South Florida, Tampa, USA.
[4] Division of Life Science, Hong Kong University of Science & Technology, Hong Kong SAR, China.
Hyperlipidemia is referred to as hypercholesterolemia, hypertriglyceridemia, or both in combined hyperlipidemia. Here, a novel mouse model of combined hyperlipidemia is described. Mice were orally given a single dose of a modeling agent (MA) made of a mixture of schisandrin B/cholesterol/bile salts (1/2/0.5 g/kg) suspended in olive oil. MA treatment increased serum triglycerides (TG) and total cholesterol (TC) (up to 422% and 100% at 12 - 96 h post-treatment, respectively) and hepatic TG and TC (up to 220% and 26%, respectively) in a time- and dose-dependent manner, associated with elevation of high-density lipoprotein and low-density lipoprotein levels. Serum alanine/aspartate aminotransferase activities, indicators of liver cell damage, were also elevated (up to 198%) at 48 and 72 h post-MA treatment. Fenofibrate blocks MA-induced hyperlipidemia, lipid accumulation in the liver, as well as liver injury. Oral administration of a mixture of schisandrin B, cholesterol, and bile salt could generate an interesting mouse model of combined hyperlipidemia associated with hepatic steatosis and steatohepatitis.