Ginsenoside Rd prevents glutamate‐induced apoptosis in rat cortical neurons

1. The role of voltage‐independent Ca²⁺ entry in cell apoptosis has recently received considerable attention. It has been found that ginsenoside Rd significantly inhibits voltage‐independent Ca²⁺ entry. The aim of the present study was to investigate the protective effects of ginsenoside Rd against glutamate‐induced apoptosis of rat cortical neurons.

2. Ginsenoside Rd significantly reduced glutamate‐induced apoptotic morphological changes and DNA laddering. In comparison, nimodipine only had a weak effect.

3. Ginsenoside Rd (1, 3 and 10 μmol/L) concentration‐dependently inhibited caspase 3 activation and expression of the p20 subunit of active caspase 3 (by 30 ± 10%, 41 ± 9% and 62 ± 19%, respectively, compared with glutamate alone; P < 0.05), whereas 1 μmol/L nimodipine had no effect.

4. Glutamate decreased cell viability to 37.4 ± 4.7 (n = 8) and evoked cell apoptosis. Ginsenoside Rd (1, 3, 10 and 30 μmol/L) concentration‐dependently inhibited glutamate‐induced cell death, increased cell viability and reduced apoptotic percentage (from 47.5 ± 4.9% to 37.4 ± 6.9%, 28.3 ± 5.2% and 22.5 ± 5.6%, respectively; P < 0.05). At 1 μmol/L, nimodipine had no effect on cell viability. Furthermore, although 1, 3, 10, 30 and 60 μmol/L ginsenoside Rd concentration‐dependently inhibited glutamate‐induced Ca²⁺ entry by 8 ± 2%, 24 ± 4%, 40 ± 7%, 49 ± 8% and 50 ± 8% (P < 0.05), respectively, nimodipine had no effect.

5. In conclusion, the results indicate that ginsenoside Rd prevents glutamate‐induced apoptosis in rat cortical neurons and provide further evidence of the potential of voltage‐independent Ca²⁺ channel blockers as new neuroprotective drugs for the prevention of neuronal apoptosis and death induced by cerebral ischaemia.