Pretreating female Balb/c mice with schisandrin B (Sch B) at increasing daily doses (1-4 mmol/kg) for 3 days caused dose-dependent increases in hepatic glutathione S-transferase (GST) and glutathione reductase (GRD) activities. However, the activities of glucose-6-phosphate dehydrogenase (G6PDH), Se-glutathione peroxidase (GPX), and gamma-glutamylcysteine synthetase (GCS) were down-regulated to varying degrees in a dose-dependent manner. While there were biphasic changes in hepatic reduced glutathione (GSH) level as well as susceptibility of hepatic tissue homogenates to in vitro peroxide-induced GSH depletion, a gradual decrease in hepatic malondialdehyde content was observed. The beneficial effect of Sch B on the hepatic GSH anti-oxidant system became more evident after CCl4 challenge. The same Sch B pretreatment regimen caused a dose-dependent protection against carbon tetrachloride (CCl4)-induced hepatotoxicity. The hepatoprotection was associated with significant enhancement in hepatic GSH status, as indicated by the substantial increase in tissue GSH levels and the corresponding decrease in susceptibility of tissue homogenates to GSH depletion. Where the activities of GST and GRD were increased linearly over non-CCl4 control values, there was also a gradual elevation in G6PDH activity upon administration of increasing doses of Sch B. In contrast, GPX activity was moderately down-regulated. The ensemble of results suggests that the hepatoprotection afforded by Sch B pretreatment may mainly be attributed to the enhancement in the functioning of the hepatic GSH anti-oxidant system, possibly through stimulating the activities of GSH related enzymes.

The effect of a lignan-enriched extract of the fruits of Schisandra chinensis (FS) on hepatic glutathione (GSH) status was examined in both control and carbon tetrachloride (CCl4)-treated rats. FS treatment caused a dose-dependent enhancement in hepatic GSH status, as evidenced by significant increases in hepatic GSH level and activities of hepatic glucose-6-phosphate and glutathione reductase (GRD), as well as a decreased susceptibility of hepatic tissue homogenates to in vitro peroxide-induced GSH depletion. The beneficial effect of FS treatment on hepatic GSH status became more evident after CCl4 challenge. Pretreating rats with FS extract at increasing daily doses ranged from 0.2 to 3.2 g/kg for 3 days caused a dose-dependent protection against the CCl4-induced impairment in hepatic GSH status. The enhancement in hepatic GSH status was associated with corresponding decreases in tissue malondialdehyde levels and plasma alanine aminotransferases activities, indicating a significant reduction in the extent of oxidative hepatocellular damage. Our results indicate that the molecular mechanism of hepatoprotection afforded by FS pretreatment may involve the facilitation of GSH regeneration via the GRD-catalyzed and NADPH-mediated reaction.

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