The effects of ginsenosides Rg3(R), Rg3(S) and Rg5/Rk1 (a mixture of Rg5 and Rk1, 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 Rg3(R), Rg3(S) or Rg5/Rk1, 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 Rg3(S) and Rg5/Rk1. Among the three ginsenosides tested in this study, Rg5/Rk1 enhanced the memory function of mice most effectively in both the ethanoland scopolamine-induced amnesia models. Moreover, the latency period of the Rg5/Rk1-treated mice was 1.2 times longer than that of the control (no amnesia) group in both models, implying that Rg5/Rk1 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. Rg3(S) and Rg5/Rk1 exhibited a more potent inhibition of excitotoxicity than did Rg3(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 Rg3(S) and Rg5/Rk1 significantly reversed the memory dysfunction induced by ethanol or scopolamine, and their neuroprotective actions against excitotoxicity may be attributed to their memory enhancing effects.

Phlorotannins, the polyphonic compounds found in brown Eisenia and Ecklonia algae, have several pharmacologically beneficial effects such as anti-inflammation. In addition, our recent data show that these compounds may improve the cognitive functions of aged humans suggesting the potential ability to enhance memory in several neurodegenerative disorders. To examine the experimental hypothesis that two effective components of Ecklonia cava, dieckol and phlorofucofuroeckol (PFF), have memory-enhancing abilities, both were administered orally to mice before a passive avoidance test. The repeated administration of either dieckol or PFF dose-dependently reduced the inhibition of latency by the administration of ethanol. To investigate the mode of memory-enhancing actions, the levels of major central neurotransmitters in three different regions (striatum, hippocampus, and frontal cortex) of the mouse brain were measured. The levels of some of the neurotransmitters were significantly changed by ethanol. Both dieckol and PFF altered the levels of some neurotransmitters modified by the ethanol treatment. It is noteworthy that both dieckol and PFF increased the level of acetylcholine, and they exerted anticholinesterase activities. Overall, the memory-enhancing abilities of dieckol and PFF may result from, at least in part, the increment of the brain level of acetylcholine by inhibiting acetylcholinesterase.