Gensenosides, the active ingredients of Chinese herbal medicine Panax ginseng, have a wide spectrum of medical effects, such as anti-tumorigenic, angiosuppressive, adaptogenic, and anti-fatigue activities. In the present study, we have investigated the neuroprotective effect of 20(R)-ginsenoside Rg(3) (20(R)-Rg(3)) against transient focal cerebral ischemia in male Sprague-Dawley (SD) rats. The middle cerebral artery was occluded for 2h in rats and then reperfused for 24h. The behavioral disturbance was evaluated according to neurological deficit scores, and the infarct volumes were evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining; in addition, ischemia-mediated apoptosis was examined using the method of terminal deoxynucleotidyl transferase (TdT)-mediated d-UTP nick end labeling (TUNEL). The expressions of calpain I and caspase-3 mRNA in hippocampal CA1 region were further assayed using in situ hybridization, in order to clarify the neuroprotective mechanism of 20(R)-Rg(3). 20(R)-Rg(3) at the doses of 10 and 20mgkg(-1) i.p., but not 5mgkg(-1), showed significant neuroprotective effect in rats against focal cerebral ischemic injury by markedly reducing cerebral infarct volumes and degrading infarct rate of TTC-stained coronal brain sections, and improving behavior of the animals. Our results also suggested that 20(R)-Rg(3) (10 and 20mgkg(-1)) could significantly suppress the expressions of calpain I and caspase-3 mRNA. These results indicated that 20(R)-Rg(3) attenuates the neuronal apoptosis caused by cerebral ischemia-reperfusion injury and its neuprotective effect may be involved in the downregulation of calpain I and caspase-3.
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