Protective effects of ginsenoside Rg2 against glutamate-induced neurotoxicity in PC12 cells.
We investigated the effect of ginsenoside Rg2 on neurotoxic activities induced by glutamate in PC12 cells. The cells were incubated with glutamate (1 mmol/L), glutamate and ginsenoside Rg2 (0.05, 0.1, 0.2 mmol/L) or nimodipine (5 micromol/L) for 24 h. The cellular viability was assessed by MTT assay. The lipid peroxidation products malondialdehyde (MDA) and nitrogen oxide (NO) were measured by a spectrophotometric method. Fura-2/AM, as a cell permeable fluorescent probe for Ca2+, was used to detect intracellular Ca2+ concentration ([Ca2+]i) using a monespectrofluorometer. Immunocytochemical techniques were employed to check the protein expression levels of calpain II, caspase-3 and beta-amyloid (Abeta)1-40 in PC12 cells. The results showed that glutamate decreased the cell viability, increased [Ca2+]i, lipid peroxidation (the excessive production of MDA, NO) and the protein expression levels of calpain II, caspase-3 and Abeta1-40 in PC12 cells. Ginsenoside Rg2 significantly attenuated glutamate-induced neurotoxic effects upon these parameters at all doses tested. Our study suggests that ginsenoside Rg2 has a neuroprotective effect against glutamate-induced neurotoxicity through mechanisms related to anti-oxidation and anti-apoptosis. In addition, the inhibitory effect of ginsenoside Rg2 against the formation of Abeta1-40 suggests that ginsenoside Rg2 may also represent a potential treatment strategy for Alzheimer's disease.
Li
Na
N
Department of Physiology, Medical College of Qingdao University, Qingdao 266071, PR China.
Liu
Bin
B
Dluzen
Dean E
DE
Jin
Yi
Y
D000544:Alzheimer Disease / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002154:Calpain / Q000187:drug effects / Q000378:metabolism; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D036145:Ginsenosides / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D018698:Glutamic Acid / Q000633:toxicity; D015227:Lipid Peroxidation / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000188:drug therapy*; D009553:Nimodipine / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D005894:Panax / Q000737:chemistry*; D010446:Peptide Fragments / Q000187:drug effects / Q000378:metabolism; D051381:Rats
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D002121:Calcium Channel Blockers; D036145:Ginsenosides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D018698:Glutamic Acid; D009553:Nimodipine; C026474:ginsenoside Rg2; D002154:Calpain; D053148:Caspase 3; D002118:Calcium