title: Abeta(25-35)-induced memory impairment, axonal atrophy, and synaptic loss are ameliorated by M1, A metabolite of protopanaxadiol-type saponins.
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-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.
authors.affiliation: 1Research Center for Ethnomedicines, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Tohda
authors.forename: Noriaki
authors.initials: N
authors.lastname: Matsumoto
authors.forename: Kun
authors.initials: K
authors.lastname: Zou
authors.forename: Meselhy R
authors.initials: MR
authors.lastname: Meselhy
authors.forename: Katsuko
authors.initials: K
authors.lastname: Komatsu
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D001284:Atrophy; D001369:Axons / Q000187:drug effects / Q000473:pathology*; D005260:Female; D036145:Ginsenosides / Q000737:chemistry / Q000494:pharmacology*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced* / Q000517:prevention & control* / Q000523:psychology; D051379:Mice; D009043:Motor Activity; D016501:Neurites / Q000187:drug effects / Q000648:ultrastructure; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000633:toxicity; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012502:Sapogenins / Q000494:pharmacology*; D012503:Saponins / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects / Q000473:pathology*; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D036145:Ginsenosides; D010446:Peptide Fragments; D012502:Sapogenins; D012503:Saponins; D014315:Triterpenes; C074636:amyloid beta-protein (25-35); C442759:ginsenoside Rb1; C062916:protopanaxadiol