We previously screened neurite outgrowth activities of several Ginseng drugs in human
neuroblastoma, and demonstrated that
protopanaxadiol (
ppd)-type
saponins were active constituents. Since
ppd-type
saponins are known to be completely metabolized to
20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol (M1) by intestinal bacteria when taken orally, M1 and
ginsenoside Rb1, as a representative of
ppd-type
saponins, were examined for
cognitive disorder. In a mouse model of
Alzheimer's disease (AD) by Abeta(25-35) i.c.v. injection, impaired spatial memory was recovered by p.o. administration of
ginsenoside Rb1 or M1. Although the expression levels of phosphorylated NF-H and
synaptophysin were reduced in the cerebral cortex and the hippocampus of Abeta(25-35)-injected mice, their levels in
ginsenoside Rb1- and M1-treated mice were almost completely recovered up to control levels. Potencies of the effects were not different between
ginsenoside Rb1 and M1 when given orally, suggesting that most of the
ginsenoside Rb1 may be metabolized to M1, and M1 is an active principal of
ppd-type
saponins for the memory improvement. In cultured rat cortical neurons, M1 showed extension activity of axons, but not dendrites. The axon-specific outgrowth was seen even when neuritic
atrophy had already progressed in response to administration of Abeta(25-35) as well as in the normal condition. These results suggest that M1 has axonal extension activity in degenerated neurons, and improve
memory disorder and synaptic loss induced by Abeta(25-35). M1 was shown to be effective in vitro and in vivo, indicating that Ginseng drugs containing
ppd-type
saponins may reactivate neuronal function in AD by p.o. administration.