Ginsenoside Rg1 activated CaMKⅡα mediated extracellular signal-regulated kinaselmitogen activated protein kinase signaling pathway

Aim： We carried out this study to investigate the effect of ginsenoside Rg1 on the extracellular signal-regulated kinase/mitogen activated protein kinase （ERK/ MAPK） pathway for understanding its effect on synaptic platicity. Methods： Western blotting and immunostaining were used to examine the phosphorylation of ERK1/2, CaMKⅡα and cAMP response element binding protein （CREB） in PC 12 cells and synaptosomes. The confocal microscopy and fluorescent indicator Fluo-3 was applied to observe the intracellular calcium ion flux. Results： The phosphorylation of ERK1/2 in PC 12 cells and synaptosomes incubated with Rg1 was increased and reached maximum at 4 min. Rg1 also promoted the transient enhancement of upstream calcium ion and activated CaMKⅡα, which reached maximum at 2 min. CREB, the downstream protein, was phosphorylated within 8 min in PC12 cells after being incubated with Rg1. Moreover, KN93 partially inhibited the activation of ERK1/2, and PD98059 also partially blocked the phosphorylation of CREB. Conclusions： Rg1 activated ERK/MAPK pathway by CaMKⅡα, and the activation of CREB was not only dependent on ERK induced by Rg1, which may provide an explanation for the effect of Rg1 on long-term potentiation.