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 micromol/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 micromol/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.