Schisandrin B (Sch B) is the most abundant, active dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis (FS), a traditional Chinese herb clinically used for the treatment of viral and chemical hepatitis.
1)A recent study from our laboratory has demonstrated that long-term treatment with Sch B was able to enhance mitochondrial antioxidant status and the resistance to Ca 2ϩ -induced mitochondrial permeability transition (PT) in an ageindependent manner in various rat organs including the heart and brain.2) The Sch B-induced enhancement of mitochondrial protective parameters in the heart was associated with the protection against myocardial ischemia/reperfusion (I/R) injury in both young and middle-aged rats.2) Given that the maintenance of mitochondrial antioxidant status and structural integrity is crucial for cell survival, 3) Sch B has been proposed to be used as a universal cell protectant against tissue damage caused by endogenous and exogenous oxidants.
2)While the protection of Sch B against I/R injury has been demonstrated in the heart, 2,4) it is still unclear whether Sch B treatment can produce any beneficial effect on cerebral I/R injury.In the present study, we investigated the effect of longterm treatment with Sch B on cerebral I/R injury in rats. To elucidate the biochemical mechanism involved in the cerebroprotection against I/R injury, cerebral mitochondrial antioxidant status as well as mitochondrial structural integrity were assessed in control and Sch B-treated rats, without or with I/R challenge.
MATERIALS AND METHODS
ChemicalsReduced glutathione (GSH), oxidized glutathione, glutathione reductase, cytochrome c, a-tocopherol (a-TOC), cyclosporin A (Cs A) and 2,3,5-triphenyl tetrazolium chloride (TTC) were purchased from Sigma Chemical Co. (St. Louis, MO, U.S.A.). All other chemicals were of analytical grade. Solvents used for HPLC were of HPLC grade.Herbal Material Dried FS was imported from mainland China. It was authenticated and supplied by a commercial dealer (Lee Hoong Kee Ltd.) in Hong Kong. Sch B was purified from the petroleum ether extract of FS, with the purity being higher than 95% as determined by HPLC analysis.
5)Animal Care Adult female Sprague-Dawley rats (8-10 weeks; 200-250 g) were maintained under a 12-h dark/light cycle at about 22°C, and allowed food and water ad libitum. Experimental protocols were approved by the Research Practice Committee at the Hong Kong University of Science & Technology.Drug Treatment Animals were randomly divided into groups, with five animals in each. In the Sch B treatment groups, rats were intragastrically administered with Sch B (dissolved/suspended in olive oil) at a daily dose of 1, 10 or 30 mg/kg from day 1 to day 15 of the experiment. This dosage regimen was found to be effective in protecting against myocardial ischemia/reperfusion injury in rats.2) Sch B-untreated animals received the vehicle (i.e. olive oil) only. The rat model of cerebral I/R injury was modified from that of Ischikawa and Konishi.6) Phenobarbita...