We previously found that
ginsenoside Rd (Rd), one of the major active ingredients in Panax ginseng, protects neuronal cells from
hydrogen peroxide and
oxygen-
glucose deprivation, an in vitro model of
cerebral ischemia. In this study, we examined the protective effects of Rd in an animal model of focal
cerebral ischemia. Rats administered with Rd or vehicle were subjected to transient
middle cerebral artery occlusion (MCAO). Rd (50 mg/kg) significantly reduced the
infarct volume by 52.8%. This reduction of injury volume was associated with an improvement in neurological function and was sustained for at least 2 weeks after the induction of
ischemia. To evaluate the underlying mechanisms of Rd against
stroke, brain tissues were assayed for mitochondrial
enzyme activities, mitochondrial membrane potential (
MMP), production of
reactive oxygen species (ROS), energy metabolites, and apoptosis. Rd markedly protected mitochondria as indicated by preserved respiratory chain complex activities and
aconitase activity, lowered mitochondrial
hydrogen peroxide production, and hyperpolarized
MMP. Microdialysis results illustrated that Rd significantly decreased the accumulation of
lactate, the end product of anaerobic glycolysis, and increased
pyruvate, the end product of aerobic glycolysis, hence inducing a lower
lactate/
pyruvate ratio. Additionally, in vitro studies further exhibited that Rd protected isolated mitochondria from
calcium-induced damage by attenuating mitochondrial swelling, preserving
MMP and decreasing ROS production. Moreover, Rd treatment reduced mitochondrial release of
cytochrome c (CytoC) and
apoptosis-inducing factor (AIF), thereby minimizing mitochondria-mediated apoptosis following
ischemia. In conclusion, these findings demonstrated that Rd exerts
neuroprotective effects in transient focal
ischemia, which may involve an integrated process of the mitochondrial protection, energy restoration and inhibition of apoptosis.