Promotion of axonal maturation and prevention of memory loss in mice by extracts of Astragalus mongholicus.
OBJECTIVE
Neurons with atrophic neurites may remain alive and therefore may have the potential to regenerate even when neuronal death has occurred in some parts of the brain. This study aimed to explore effects of drugs that can facilitate the regeneration of neurites and the reconstruction of synapses even in severely damaged neurons.


METHODS
We investigated the effects of extracts of Astragalus mongholicus on the cognitive defect in mice caused by injection with the amyloid peptide Abeta(25-35). We also examined the effect of the extract on the regeneration of neurites and the reconstruction of synapses in cultured neurons damaged by Abeta(25-35).


RESULTS
A. mongholicus extract (1 g kg(-1) day(-1) for 15 days, p.o.) reversed Abeta(25-35)-induced memory loss and prevented the loss of axons and synapses in the cerebral cortex and hippocampus in mice. Treatment with Abeta(25-35) (10 microM) induced axonal atrophy and synaptic loss in cultured rat cortical neurons. Subsequent treatment with A. mongholicus extract (100 microg/ml) resulted in significant axonal regeneration, reconstruction of neuronal synapses, and prevention of Abeta(25-35)-induced neuronal death. Similar extracts of A. membranaceus had no effect on axonal atrophy, synaptic loss, or neuronal death. The major known components of the extracts (astragalosides I, II, and IV) reduced neurodegeneration, but the activity of the extracts did not correlate with their content of these three astragalosides.


CONCLUSIONS
A. mongholicus is an important candidate for the treatment of memory disorders and the main active constituents may not be the known astragalosides.
Tohda
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Division of Biofunctional Evaluation, Research Center for Ethnomedicine, Institute of Natural Medicine, University of Toyama, Toyama, Japan. chihiro@inm.u-toyama.ac.jp
Tamura
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T
Matsuyama
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Komatsu
K
K
D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D027883:Astragalus Plant / Q000737:chemistry*; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003072:Cognition Disorders / Q000139:chemically induced / Q000517:prevention & control; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects / Q000503:physiopathology; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000517:prevention & control*; D051379:Mice; D020932:Nerve Growth Factor / Q000494:pharmacology; D016900:Neurofilament Proteins / Q000032:analysis; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage / Q000633:toxicity; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D012153:Retention, Psychology / Q000187:drug effects; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects; D016708:Synaptophysin / Q000032:analysis; D013702:Temporal Lobe / Q000737:chemistry / Q000187:drug effects / Q000503:physiopathology; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D016900:Neurofilament Proteins; D010446:Peptide Fragments; D010936:Plant Extracts; D012503:Saponins; D016708:Synaptophysin; D014315:Triterpenes; C074636:amyloid beta-protein (25-35); C051774:neurofilament protein H; C052064:astragaloside A; D020932:Nerve Growth Factor