Overcoming several neurodegenerative diseases by traditional medicines

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Yakugaku Zasshi. 2008 Aug;128(8):1159-67.

Overcoming several neurodegenerative diseases by traditional

medicines.

Tohda C.

Division of Biofunctional Evaluation, Research Center for

Ethnomedicine, Insitute of Natural Medicine, University of Toyama.

Ashwagandha (root of Withania somnifera) 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 Abeta(25-35)-induced injury. In vivo, oral withanolide

A, withanoside IV, and withanoside VI (10 mumol/kg/day for 12 days)

improved Abeta(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 (10 mumol/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.