Withanoside IV and its active metabolite, sominone, attenuate Abeta(25-35)-induced neurodegeneration.
At the present, medication of dementia is limited to symptomatic treatments such as the use of cholinesterase inhibitors. To cure dementia completely, that is regaining neuronal function, reconstruction of neuronal networks is necessary. Therefore, we have been exploring antidementia drugs based on reconstructing neuronal networks in the damaged brain and found that withanoside IV (a constituent of Ashwagandha; the root of Withania somnifera) induced neurite outgrowth in cultured rat cortical neurons. Oral administration of withanoside IV (10 micromol/kg/day) significantly improved memory deficits in Abeta(25-35)-injected (25 nmol, i.c.v.) mice and prevented loss of axons, dendrites, and synapses. Sominone, an aglycone of withanoside IV, was identified as the main metabolite after oral administration of withanoside IV. Sominone (1 microM) induced axonal and dendritic regeneration and synaptic reconstruction significantly in cultured rat cortical neurons damaged by 10 microM Abeta(25-35). These data suggest that orally administrated withanoside IV may ameliorate neuronal dysfunction in Alzheimer's disease and that the active principle after metabolism is sominone.
Kuboyama
Tomoharu
T
Division of Biofunctional Evaluation, Research Center for Ethnomedicine, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan.
Tohda
Chihiro
C
Komatsu
Katsuko
K
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004875:Ergosterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D013058:Mass Spectrometry; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology; D009416:Nerve Regeneration / Q000187:drug effects; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D010446:Peptide Fragments / Q000633:toxicity*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects; D032341:Withania / Q000737:chemistry*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010936:Plant Extracts; C074636:amyloid beta-protein (25-35); C523922:withanoside IV; D004875:Ergosterol