Ginsenoside Rd prevents glutamate-induced apoptosis in rat cortical neurons.

Summary 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.