Ginsenoside Rg1 protects against 6-OHDA-induced toxicity in MES23.5 cells via Akt and ERK signaling pathways.
OBJECTIVE
The present study was designed to investigate the neuroprotective effects of ginsenoside Rg1 against 6-hydroxydopamine (6-OHDA)-induced toxicity in MES23.5 cells and their possible mechanisms.


METHODS
MES23.5 cells were treated with or without Rg1 for 24h before exposure to 6-OHDA. Cell viability was determined by MTS assay. The gene and protein expressions of Bcl-2 were detected by real time RT-PCR and western blotting. Phosphorylation of Akt and ERK1/2 were examined by western blotting.


RESULTS
Pretreatment with ginsenoside Rg1 had obvious neuroprotective effects on cell viability against 6-OHDA-induced toxicity. 6-OHDA decreased the gene and protein expressions of Bcl-2. These effects could be reversed by Rg1 pretreatment. Potential cell signaling candidates involved in this neuroprotective effect were examined. 6-OHDA significantly inhibited the phosphorylation of Akt and increased the phosphorylation of ERK1/2 in MES23.5 cells. Pretreatment with ginsenoside Rg1 could increase the Akt phosphorylation and inhibit the ERK1/2 phosphorylation induced by 6-OHDA. Further study revealed that LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3-K), attenuated the neuroprotective effect of Rg1 on cell viability against 6-OHDA-induced toxicity.


CONCLUSIONS
Taken together, our results strongly suggest that ginsenoside Rg1 has neuroprotective effects against 6-OHDA-induced toxicity in MES23.5 cells. Its mechanism includes the up-regulation of Bcl-2 gene expression, the activation of Akt phoshphorylation as well as the inhibition of ERK1/2 phosphorylation induced by 6-OHDA.
Department of Physiology, Medical College of Qingdao University, No. 308 Ningxia Road, Boya Building, Qingdao, Shandong 266071, PR China.
Ke-Li
KL
Ge
Wen-Fang
WF
Chen
Jun-Xia
JX
Xie
Man-Sau
MS
Wong
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D019254:Genes, bcl-2 / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D048789:Phytoestrogens / Q000494:pharmacology; D008517:Phytotherapy; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013997:Time Factors
D036145:Ginsenosides; D018696:Neuroprotective Agents; D000081082:Phosphoinositide-3 Kinase Inhibitors; D048789:Phytoestrogens; D019253:Proto-Oncogene Proteins c-bcl-2; D016627:Oxidopamine; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C035054:ginsenoside Rg1