title: Ginsenoside Rd prevents glutamate-induced apoptosis in rat cortical neurons.
abstract: 1. The role of voltage-independent Ca(2+) entry in cell apoptosis has recently received considerable attention. It has been found that ginsenoside Rd significantly inhibits voltage-independent Ca(2+) 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 micromol/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 micromol/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 micromol/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 micromol/L, nimodipine had no effect on cell viability. Furthermore, although 1, 3, 10, 30 and 60 micromol/L ginsenoside Rd concentration-dependently inhibited glutamate-induced Ca(2+) 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 Ca(2+) channel blockers as new neuroprotective drugs for the prevention of neuronal apoptosis and death induced by cerebral ischaemia.
authors.affiliation: Department of Pharmacy, Third Affiliated Hospital, Guangzhou, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Liang
authors.forename: Yong-Bo
authors.initials: YB
authors.lastname: Tang
authors.forename: Jia-Guo
authors.initials: JG
authors.lastname: Zhou
authors.forename: Yong-Yuan
authors.initials: YY
authors.lastname: Guan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects*; D036145:Ginsenosides / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009553:Nimodipine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002121:Calcium Channel Blockers; D036145:Ginsenosides; D018696:Neuroprotective Agents; D018698:Glutamic Acid; D009553:Nimodipine; D053148:Caspase 3; D002118:Calcium; C049863:ginsenoside Rd