伝統薬物による神経変性疾患の克服 : 治療薬開発と病態機序の解明に向けて

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概要

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• Ashwagandha (root of Withania somniferd) has been used for many purposes, it is mainly considered a tonic in traditional Ayurvedic medicine. This review focuses on the effects of compounds isolated from Ashwagandha on dementia models and on the spinal cord injury model. Our study demonstrated that the active constituents, withanolide A, withanoside IV, and withanoside VI, restored presynapses and postsynapses, in addition to both axons and dendrites in cortical neurons after Aβ(25-35) -induced injury. In vivo, oral withanolide A, withanoside IV, and withanoside VI (10μmol/kg/day for 12 days) improved Aβ (25-35) -induced memory impairment, neurite atrophy, and synaptic loss in the cerebral cortex and hippocampus in mice. Since spinal cord injury (SCI) is also difficult to treat, and therefore practical and curable strategies for SCI are desired. Oral treatment with withanoside IV improved locomotor functions in mice with SCI. In mice treated with withanoside IV (10μmol/kg/day for 21 days), the axonal density and peripheral nervous system myelin level increased. The loss of CNS myelin and increase in reactive gliosis were not affected by withanoside IV. Additionally, sominone, an aglycone of withanoside IV, was identified as the main metabolite after oral administration of withanoside IV in mice. Withanolide A, withanoside IV, and withanoside VI are therefore important candidates for the therapeutic treatment of neurodegenerative diseases. In particular, withanoside IV was shown to control neurons as well as glial cells for reconstruction neuronal networks. To clarify key events in overcoming neurodegeneration, we are now studying the molecular targets and signal cascades of sominone.

• 2008-08-01

著者

• 東田 千尋

  富山大学和漢医薬学総合研究所 民族薬物研究センター薬効解析部

関連論文

• アルツハイマー病に有効な漢方薬 (特集 増加する一般漢方製剤)
• 伝統薬物による神経変性疾患の克服 : 治療薬開発と病態機序の解明に向けて
• 軸索およびシナプス形成の促進による神経変性疾患の克服 : 治療薬開発と病態機序の解明に向けて

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