novel experimental model of acute hypertriglyceridemia
induced by schisandrin B
PAN Si-Yuan ; HANG DONG ; HAN Yi-Fan ; LI Wen-Yuan; ZHAO Xing-Ye; KO Kam-Ming ;
Department of Pharmacology, Beijing University of Chinese Medicine, Beijing 100102, CHINE, Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, HONG-KONG
Mice were intragastrically treated with single doses (0.05-0.8 g/kg) ofschisandrin B (a dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis). Twenty-four hours after schisandrin B administration, the serum triglyceride level was increased by 10-235% in a dose-dependent manner. However, the serum low density lipoprotein cholesterol level was significantly decreased by 28% at a dose of 0.8 g/kg. When given once daily (0.01-0.2 g/kg) for 4 days, schisandrin B also dose-dependently elevated the serum triglyceride level (17-134%). Kinetics parameters estimated by Scott's plot analysis of schisandrin B-induced changes in serum and hepatic triglyceride levels were determined: serum-Emax (maximal effect) = 6 mmol/L (384% increase, P<0.001); KD (affinity)=0.59 mmol/kg; pD2 (an index of affinity)=6.62; liver-Emax=21 μmol/g (68% increase, P<0.001); KD=0.37 mmol/kg; pD2=6.83. The efficacy ofschisandrin B in increasing the triglyceride level was 5.6-fold higher in serum than in liver tissue. Fenofibrate (0.2 g/kg) treatment, when in combination with schisandrin B (0.2 g/kg), for 4 days significantly reduced the schisandrin B-induced increase in serum triglyceride level (by 81%, P<0.001). Hepatic triglyceride level was also decreased (by 100%, P<0.001) by co-treatment with fenofibrate. Our results suggest that schisandrin B treatment can be used to establish a mouse model of acute hypertrigylceridemia.