Fructus schisandrae (FS), the fruit of Schisandra chinensis, has been used as tonic and sedative in traditional Chinese medicine. Previous studies from our laboratory have demonstrated that schisandrin B (Sch B), a dibenzocyclooctadiene derivative isolated from FS, could produce antioxidant effect on rodent liver and heart. A mouse model of tert-butylhydroperoxide (t-BHP) induced cerebral toxicity was adopted for examining the antioxidant potential of Sch B in the brain. Intracerebroventricular injection of t-BHP caused a time-dependent increase in mortality rate in mice. The t-BHP toxicity was associated with an increase in the extent of cerebral lipid peroxidation and a transient impairment in cerebral glutathione antioxidant status, as evidenced by the abrupt decrease in reduced glut...[ Read more ]

Fructus schisandrae (FS), the fruit of Schisandra chinensis, has been used as tonic and sedative in traditional Chinese medicine. Previous studies from our laboratory have demonstrated that schisandrin B (Sch B), a dibenzocyclooctadiene derivative isolated from FS, could produce antioxidant effect on rodent liver and heart. A mouse model of tert-butylhydroperoxide (t-BHP) induced cerebral toxicity was adopted for examining the antioxidant potential of Sch B in the brain. Intracerebroventricular injection of t-BHP caused a time-dependent increase in mortality rate in mice. The t-BHP toxicity was associated with an increase in the extent of cerebral lipid peroxidation and a transient impairment in cerebral glutathione antioxidant status, as evidenced by the abrupt decrease in reduced glutathione (GSH) level and the inhibition of Se-glutathione peroxidase (GSH-Px) activity during the early phase of t-BHP challenge. Findings of the ability of buthionine sulfoximine (BSO) or α-lipoic acid pretreatment to increase or decrease, respectively, the susceptibility to t-BHP induced toxicity suggest the crucial importance of maintenance of cerebral GSH redox status, presumably through GSH synthesis, in protecting against t-BHP induced cerebral toxicity.

Sch B pretreatment protected against t-BHP induced toxicity, with resultant zero mortality rate up to 60 min post-challenge at the highest dose tested. The protection afforded by Sch B pretreatment was associated with the decrease in the extent of lipid peroxidation and enhancement in glutathione antioxidant status. The ability of BSO treatment to partly abrogate the Sch B protection suggests the involvement of enhancement in GSH synthesis, under oxidative stress condition, in the protective action produced by Sch B.

Pretreatment with dimethyldiphenylbicarboxylate (DDB), a synthetic intermediate of schisandrin C (also a dbenzocyclooctadiene derivative), protected against t-BHP toxicity, but at a lesser extent than that of Sch B. The ability of Sch B, but not DDB, to enhance the GSH regeneration capacity in brain tissue suggests that the varied effect produced by Sch B and DDB may be related to their differential ability in enhancing tissue glutathione antioxidant status.

Sch B pretreatment also protected the PC12 cell culture against hydrogen peroxide induced cell injury. The ensemble of results obtained from the present study has demonstrated the antioxidant potential of Sch B pretreatment in brain tissue, both in vivo and in vitro. The ability of Sch B to enhance cerebral glutathione antioxidant status suggests the application of this compound or its related preparations for the prevention and/or treatment of oxidative stress-induced brain injury.