Abstract
Schisandrin B, an active ingredient isolated from the fruit of Schisandra chinensis, increased serum and hepatic triglyceride levels in mice. In the present study, the effective kinetics of schisandrin B on serum/hepatic triglyceride and total cholesterol levels in mice without and with the influence of fenofibrate were investigated. Parameters on hepatic index (the ratio of liver weight to body weight × 100) were also analyzed. Mice were intragastrically treated with schisandrin B at a single dose of 0.2, 0.4, 0.8, or 1.6 g/kg, without or with fenofibrate pretreatment (0.1 g/kg/day for 4 days, p.o.). Twenty-four hours after schisandrin B treatment, serum/hepatic triglyceride and total cholesterol levels were measured. Schisandrin B treatment dose-dependently increased serum and hepatic triglyceride levels as well as hepatic index in mice. In contrast, hepatic total cholesterol levels were decreased in a dose-dependent manner in schisandrin B-treated mice. Data obtained from effective kinetics analysis indicated that the action of schisandrin B on serum triglyceride had a higher specificity than those on hepatic total cholesterol and hepatic index. While fenofibrate pretreatment inhibited the schisandrin B-induced elevation in serum triglyceride levels, it completely abrogated the elevation of hepatic triglyceride levels in schisandrin B-treated mice. The combined treatment with schisandrin B and fenofibrate decreased hepatic total cholesterol level and increased the hepatic index in an additive or semi-additive manner, respectively. In conclusion, the results of effective kinetics analysis indicated that the schisandrin B-induced hypertriglyceridemia was competitively inhibited by fenofibrate. Schisandrin B may offer the prospect of setting up a mouse model of hypertriglyceridemia and fatty liver for screening triglyceride-lowering drug candidates.
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This work was supported by a grant from the National Natural Science Foundation of China (grant no. 31071989).
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Si-Yuan Pan and Zhi-Ling Yu contributed equally to this work.
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Pan, SY., Dong, H., Guo, Bf. et al. Effective kinetics of schisandrin B on serum/hepatic triglyceride and total cholesterol levels in mice with and without the influence of fenofibrate. Naunyn-Schmiedeberg's Arch Pharmacol 383, 585–591 (2011). https://doi.org/10.1007/s00210-011-0634-x
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DOI: https://doi.org/10.1007/s00210-011-0634-x