Ginsenoside Rg1 protects neurons from hypoxic–ischemic injury possibly by inhibiting Ca2+ influx through NMDA receptors and L-type voltage-dependent Ca2+ channels

The purpose of this study is to assess the neuroprotective effect of Rg1, a ginsenoside. We measured cell viability and lactate dehydrogenase (LDH) release from primary culture of rat hippocampal neurons and electrical activities in hippocampal slices of rats, before and after the neurons were deprived of oxygen and glucose. In addition, cerebral damage was evaluated with magnetic resonance imaging after middle cerebral artery was occluded transiently. Nissl staining was used for histological observation and immunohistochemistry analysis for activated caspase-3 expression of the brain. Furthermore, calcium influx was measured with laser confocal microscopy in neurons perfused with KCl (50 mM) or N-methyl-d-aspartate (NMDA, 1 mM), or deprived of oxygen and glucose. The influences of ginsenoside Rg1 on these parameters were determined simultaneously. We found that treatment of Rg1: 1) increased the neuronal viability; 2) promoted the recovery of electrical activity in hippocampal slices; 3) reduced the release of LDH, cerebral damage area, neuronal loss and expression of caspase-3; and 4) inhibited calcium influx induced by NMDA, KCl or oxygen/glucose deprivation. However, the protective effect of Rg1 was blocked by mifepristone, an antagonist of glucocorticoid receptors. Taken together, these results suggest that ginsenoside Rg1 can reduce neuronal death, including apoptotic cell death, induced by hypoxic–ischemic insults. This neuroprotective effect is probably mediated by the activation of glucocorticoid receptors, and by the inhibition of calcium influx through NMDA receptors and L-type voltage-dependent Ca2+ channels and the resultant reduction of intracellular free Ca2+.