Schisandrin B protects against tacrine- and bis(7)-tacrine-induced hepatotoxicity and enhances cognitive function in mice

Planta Med. 2002 Mar;68(3):217-20. doi: 10.1055/s-2002-23145.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Alanine Transaminase / metabolism
  • Animals
  • Avoidance Learning / drug effects
  • Behavior, Animal / drug effects
  • Cognition / drug effects*
  • Cyclooctanes
  • Dose-Response Relationship, Drug
  • Fruit / chemistry
  • Lignans / chemistry
  • Lignans / isolation & purification
  • Lignans / pharmacology*
  • Liver / drug effects*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Polycyclic Compounds / chemistry
  • Polycyclic Compounds / isolation & purification
  • Polycyclic Compounds / pharmacology*
  • Schisandraceae*
  • Tacrine / analogs & derivatives*
  • Tacrine / toxicity*
  • alpha-Tocopherol / pharmacology

Substances

  • 1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine
  • Cyclooctanes
  • Lignans
  • Plant Extracts
  • Polycyclic Compounds
  • schizandrin B
  • Tacrine
  • Alanine Transaminase
  • alpha-Tocopherol