Schisandrin B protects against tacrine- and bis(7)-tacrine-induced hepatotoxicity and enhances cognitive function in mice.
Intragastric administration (100-200 micromol/kg) of tacrine (THA) or bis(7)-THA could cause an acute and dose-dependent increase in plasma alanine aminotransferases activity in mice at 6 h after the drug administration. The increase in plasma enzyme activity was associated with an increase in hepatic malondialdehyde level, an indirect index of oxidative tissue damage. Pretreating mice with schisandrin B (Sch B), an active dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis, at a daily dose of 0.125-0.5 mmol/kg for 3 days protected against the THA/bis(7)-THA induced hepatic oxidative damage in a dose-dependent manner. Sch B treatment (0.025-0.5 mmol/kg/day x 5) also enhanced the passive avoidance-response in mice as assessed by the step-through task experiment. The ensemble of results suggests that Sch B may be useful for reducing the potential hepatotoxicity of THA/bis(7)-THA in anti-Alzheimer's therapy.
Pan
S Y
SY
Department of Biochemistry, Hong Kong University of Science & Technology, China.
Han
Y F
YF
Carlier
P R
PR
Pang
Y P
YP
Mak
D H F
DH
Lam
B Y H
BY
Ko
K M
KM
D000410:Alanine Transaminase / Q000097:blood / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D003071:Cognition / Q000187:drug effects*; D034242:Cyclooctanes; D004305:Dose-Response Relationship, Drug; D005638:Fruit / Q000737:chemistry; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D011083:Polycyclic Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D029633:Schisandraceae; D013619:Tacrine / Q000031:analogs & derivatives* / Q000633:toxicity*; D024502:alpha-Tocopherol / Q000494:pharmacology
C122128:1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine; D034242:Cyclooctanes; D017705:Lignans; D010936:Plant Extracts; D011083:Polycyclic Compounds; C015499:schizandrin B; D013619:Tacrine; D000410:Alanine Transaminase; D024502:alpha-Tocopherol