A novel experimental model of acute hypertriglyceridemia induced by schisandrin B.
Mice were intragastrically treated with single doses (0.05-0.8 g/kg) of schisandrin 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-E(max) (maximal effect)=6 mmol/L (384% increase, P<0.001); K(D) (affinity)=0.59 mmol/kg; pD(2) (an index of affinity)=6.62; liver-E(max)=21 micromol/g (68% increase, P<0.001); K(D)=0.37 mmol/kg; pD(2)=6.83. The efficacy of schisandrin B in increasing the triglyceride level was 5.6-fold higher in serum than in liver tissue. Fenofibrate (0.2g/kg) treatment, when in combination with schisandrin B (0.2g/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.
Pan
Si-Yuan
SY
Department of Pharmacology, Beijing University of Chinese Medicine, Beijing 100102, China. si-yuan-pan@163.com
Dong
Hang
H
Han
Yi-Fan
YF
Li
Wen-Yuan
WY
Zhao
Xing-Ye
XY
Ko
Kam-Ming
KM
D000818:Animals; D034242:Cyclooctanes / Q000494:pharmacology; D004195:Disease Models, Animal; D011345:Fenofibrate / Q000494:pharmacology; D015228:Hypertriglyceridemia / Q000139:chemically induced*; D000960:Hypolipidemic Agents / Q000494:pharmacology; D017705:Lignans / Q000494:pharmacology*; D008055:Lipids / Q000032:analysis / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011083:Polycyclic Compounds / Q000494:pharmacology*
D034242:Cyclooctanes; D000960:Hypolipidemic Agents; D017705:Lignans; D008055:Lipids; D011083:Polycyclic Compounds; C015499:schizandrin B; D011345:Fenofibrate