Schisandrin B Protects Against Tacrine- and Bis(7)-tacrine-Induced Hepatotoxicity and Enhances Cognitive Function in Mice

Abstract

Intragastric administration (100 - 200 μmol/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 × 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.

Abbreviations

ALT:alanine aminotransferases

MDA:malondialdehyde

Sch B:schisandrin B

THA:tetrahyroaminoacridine

V_E:α-tocopherol

Key words

Tacrine - bis(7)-tacrine - hepatotoxicity - Schisandra chinensis - Schisandraceae - schisandrin B - cognitive enhancement

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