Ginsenoside Rg1 Protects Against 6-OHDA-Induced Toxicity Via The Activation Of The PI3K/Akt And ERK Signaling Pathways

Phytoestrogens are plant-derived compounds that structurally or functionally mimic mammalian estrogens.They have been shown to possess a variety of biological effects including antioxidant and free redical scavenging.Ginsenosides Rg1 is the principal active component of ginseng.Recently,many studies have demonstrated that Rg1 has neuroprotective and neurotrophic effects on the nervous system.Our previous study has shown that Rg1 a novel class of potent phytoestrogen and can activate insulin-like growth factor-Ⅰreceptor(IGF-IR) signaling pathway as well as can protect against the 6-OHDA-induced neurotoxicity in dopaiminergic MES23.5 cell line.Our present study aims at investigating the signaling pathways involved in the neuroprotective effects of ginsenoside Rg1 against the 6-OHDA-induced neurotoxicity in MWE23.5 cells and the blocking effects of phosphatidylinositol 3 kinase(PI3K) antagonist LY294002 or mitogen-activated protein kinase kinase(MEK) antagonist PD98059 by using MTT assay, real time RT-PCR and western blot.Results were as follows:1.Rg1 had neuroprotective effects on cell viability against 6-OHDA-induced neurotoxicity in MES23.5 cells(P＜0.05).The maximal rescue occurred at the concentration of 10^-8M.2.6-OHDA significantly decreased the protein and gene expressions of TH(P＜0.05). Rg1 pretreatment could reverse the toxic effect of 6-OHDA.3.6-OHDA significantly decreased the protein and gene expressions of Bcl-2(P＜0.05). Pretreatment with Rg1 could reverse the 6-OHDA-induced decrease of theBcl-2 expression.4.6-OHDA signifcantly decreased the Akt phosphorylation in a time dependent manner in MES23.5 cells(P＜0.05).Rg1 pretreatment could significantly increase the Akt phosphorylation.5.6-OHDA signifcantly increased the ERK phosphorylation in a time dependent manner in MES23.5 cells(P＜0.05).Rg1 pretreatment could significantly decrease the ERK phosphorylation.6.The neuroprotective effect of Rg1 on cell viability against 6-OHDA-induced toxicity was completely blocked by LY294002 or PD98059(P＜0.01).These data demonstrated that ginsenoside Rg1 have neuroprotective effects against the 6-OHDA-induced neurotoxicity in MES23.5 cells and their actions might involve activation of PI3K/Akt and ERK signaling pathways.These results not only provide new mechanism for the neuroprotective effects of Rg1,but also provide experimental evidence for the clinical application of ginsenoside Rg1 for prevention and treatment of Parkinson's disease.