Memory enhancing and neuroprotective effects of selected ginsenosides

The effects of ginsenosides Rg(3)(R), Rg(3)(S) and Rg(5)/Rk(1) (a mixture of Rg(5) and Rk(1), 1:1, w/w), which are components isolated from processed Panax ginseng C.A. Meyer (Araliaceae), on memory dysfunction were examined in mice using a passive avoidance test. The ginsenosides Rg(3)(R), Rg(3)(S) or Rg(5)/Rk(1), when orally administered for 4 days, significantly ameliorated the memory impairment induced by the single oral administration of ethanol. The memory impairment induced by the intraperitoneal injection of scopolamine was also significantly recovered by ginsenosides Rg(3)(S) and Rg(5)/Rk(1). Among the three ginsenosides tested in this study, Rg(5)/Rk(1), enhanced the memory function of mice most effectively in both the ethanol-and scopolamine-induced amnesia models. Moreover, the latency period of the Rg(5)/Rk(1)-treated mice was 1.2 times longer than that of the control (no amnesia) group in both models, implying that Rg(5)/Rk(1) may also exert beneficial effects in the normal brain. We also evaluated the effects of these ginsenosides on the excitotoxic and oxidative stress-induced neuronal cell damage in primary cultured rat cortical cells. The excitotoxicity induced by glutamate or N-methyl-D-aspartate (NMDA) was dramatically inhibited by the three ginsenosides. Rg(3)(S) and Rg(5)/Rk(1) exhibited a more potent inhibition of excitotoxicity than did Rg(3)(R). In contrast, these ginsenosides were all ineffective against the H2O2- or xanthine/xanthine oxidase-induced oxidative neuronal damage. Taken together, these results indicate that ginsenosides Rg(3)(S) and Rg(5)/Rk(1) significantly reversed the memory dysfunction induced by ethanol or scopolamine, and their neuroprotective actions against excitotoxicity may be attributed to their memory enhancing effects.