Neuroprotective effects of diallyl sulfide against transient focal cerebral ischemia via anti-apoptosis in rats

Objectives: Diallyl sulfide (DAS) is the main organosulfur component of garlic and it is known for multiple pharmacological actions. Recent studies have demonstrated that DAS has neuroprotective effects against ischemia/reperfusion injury. While some of the possible mechanisms behind this protection have been explored, its ability to inhibit apoptosis has yet to be fully explained. In the present study, the effects of DAS on focal cerebral ischemia in rats were tested and its anti-apoptotic action was explored. Methods: To examine the protective effects of DAS, focal cerebral ischemia/reperfusion was induced in rats by transient middle cerebral artery occlusion for 2 hours followed by reperfusion for 24 hours. The animals received DAS in quantities of 100, 150, and 200 mg/kg (intraperitoneal; every day), for 7 days before transient middle cerebral artery occlusion. The neurological score and infarct volume were measured at 24 hours after the end of reperfusion. Apoptotic cells were counted by terminal dUTP nick end labeling staining and apoptotic mechanisms were studied by fluorescence immunohistochemistry staining and western blot analysis. Results: For animals with induced ischemia/reperfusion, those pretreated with 200 mg/kg DAS showed an infarct volume (22.36 +/- 0.67%) significantly lower than that of the non-treated ischemia/reperfusion group (38.23 +/- 0.72%), and the percentage of terminal dUTP nick-end labeling-positive cells (23.46 +/- 1.02%) of the DAS-pretreated group was also significantly decreased compared to non-treated (36.41 +/- 1.58%). Fluorescence immunohistochemistry staining and western blot analysis indicated that DAS reduced caspase-3 expression and increased Bcl-2 expression. Conclusion: These results suggest that the mechanism by which DAS protects the brain from ischemia/reperfusion injury is related to its anti-apoptotic effects in part.