Nootropic effect of ginsenoside Rg1 and its metabolites and its signaling pathway

摘要

Aim:Ginsenoside Rg1 (G-Rg1) has been reported to improve cognitive function in ten models of memory impairment.However,there is no study on the nootropic effects of ginsenoside Rh1 (G-Rh1) and 20(S)-protopanaxatriol (Ppt).And the nootropic molecular mechanism of G-Rg1 has not been clarified completely.The emphasis of the present study will focus on the bioactivities of G-Rg1,G-Rh1 and Ppt,and elucidation of the nootropic signaling pathway of G-Rg1.Methods:Step-through passive avoidance test and electrophysiological method were used to study the bioactivities of G-Rg1,G-Ph1 and Ppt on mice and rats,respectively.Western blot,northern blot,immunohistochemistry and enzyme-link immunoassays were applied to detect Ach,cAMP,PKC,p-CREB,Fos,BDNF and PDE in hippocampus and/or cortex.Results:Both G-Rh1 and Ppt significantly ameliorated memory impairment induced by scopolamine in mice.Consistently,the electrophysiological work revealed that G-Rh1,Ppt and G-Rg1 all increased basic synaptic transmission which has direct correlation on learning and memory in the dentate gyrus of anesthetized rats,leading to the formation of long-term potentiation (LTP).Both Ppt and G-Rg1 enhanced the maintenance stage of LTP induced by high frequency stimulus (HFS).G-Rg1 up-regulated the levels of Ach,M-cholinergic receptor density,cAMP,PKC,p-CREB,BDNF and Fos,and down-regulated the activity of PDE.Conclusion:Both G-Rh1 and Ppt had nootropic action and could enhance synaptic transmission.Ppt showed more potent activity than G-Rg1 both in the behavioral or electrophysiological studies.G-Rg1 induced nootropic signaling pathway characterized by cAMP mediated intracellular cascade.