Withanoside IV and its active metabolite, sominone, attenuate Aβ(25–35)-induced neurodegeneration

Authors

  • Tomoharu Kuboyama,

    1. Division of Pharmacognosy, Institute of Natural Medicine, University of Toyama, Toyama, Japan
    2. 21st Century COE Program, University of Toyama, Toyama, Japan
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  • Chihiro Tohda,

    1. Division of Biofunctional Evaluation, Research Center for Ethnomedicine, Institute of Natural Medicine, University of Toyama, Toyama 930–0194, Japan
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  • Katsuko Komatsu

    1. Division of Pharmacognosy, Institute of Natural Medicine, University of Toyama, Toyama, Japan
    2. 21st Century COE Program, University of Toyama, Toyama, Japan
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Dr Chihiro Tohda, as above.
E-mail: chihiro@ms.toyama-mpu.ac.jp

Abstract

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 µmol/kg/day) significantly improved memory deficits in Aβ(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 µm) induced axonal and dendritic regeneration and synaptic reconstruction significantly in cultured rat cortical neurons damaged by 10 µm Aβ(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.

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