1. ¹Research Center for Ethnomedicines, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan
2. ²21st Century COE Program, Toyama Medical and Pharmaceutical University, Toyama, Japan

Correspondence: Dr Katsuko Komatsu, Research Center for Ethnomedicines, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan. Tel: +81 76 434 7645; Fax: +81 76 434 5064; E-mail: katsukok@ms.toyama-mpu.ac.jp

Received 22 August 2003; Revised 10 November 2003; Accepted 11 December 2003; Published online 10 March 2004.

Abstract

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--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 A(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 A(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 A(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 A(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.