title: Effective kinetics of schisandrin B on serum/hepatic triglyceride and total cholesterol levels in mice with and without the influence of fenofibrate.
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.
authors.affiliation: Department of Pharmacology, Beijing University of Chinese Medicine, Beijing 100102, China. siyuan-pan@163.com
authors.forename: Si-Yuan
authors.initials: SY
authors.lastname: Pan
authors.forename: Hang
authors.initials: H
authors.lastname: Dong
authors.forename: Bao-Feng
authors.initials: BF
authors.lastname: Guo
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhi-Ling
authors.initials: ZL
authors.lastname: Yu
authors.forename: Wang-Fun
authors.initials: WF
authors.lastname: Fong
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Han
authors.forename: Kam-Ming
authors.initials: KM
authors.lastname: Ko
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D034242:Cyclooctanes / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D011345:Fenofibrate / Q000494:pharmacology*; D015228:Hypertriglyceridemia / Q000139:chemically induced* / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D017705:Lignans / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011083:Polycyclic Compounds / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D032141:Schisandra / Q000737:chemistry; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
chemical_list: D034242:Cyclooctanes; D000960:Hypolipidemic Agents; D017705:Lignans; D011083:Polycyclic Compounds; D014280:Triglycerides; C015499:schizandrin B; D002784:Cholesterol; D011345:Fenofibrate