withaferin-a and Memory-Disorders

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.

Topics: Alzheimer Disease; Animals; Axons; Dendrites; Disease Models, Animal; Ergosterol; Humans; Medicine, Ayurvedic; Memory Disorders; Mice; Motor Activity; Neurodegenerative Diseases; Phytotherapy; Plant Extracts; Spinal Cord Injuries; Stimulation, Chemical; Synapses; Withania; Withanolides

Ashwagandha (Withania somnifera L.) root extract (50, 100 and 200 mg/kg; orally) improved retention of a passive avoidance task in a step-down paradigm in mice. Ashwagandha (50, 100 and 200 mg/kg; orally) also reversed the scopolamine (0.3 mg/kg)-induced disruption of acquisition and retention and attenuated the amnesia produced by acute treatment with electroconvulsive shock (ECS), immediately after training. Chronic treatment with ECS, for 6 successive days at 24 h intervals, disrupted memory consolidation on day 7. Daily administration of ashwagandha for 6 days significantly improved memory consolidation in mice receiving chronic ECS treatment. Ashwagandha, administered on day 7, also attenuated the disruption of memory consolidation produced by chronic treatment with ECS. On the elevated plus-maze, ashwagandha reversed the scopolamine (0.3 mg/kg)-induced delay in transfer latency on day 1. On the basis of these findings, it is suggested that ashwagandha exhibits a nootropic-like effect in naive and amnesic mice.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Avoidance Learning; Electroshock; Female; Herbal Medicine; Male; Maze Learning; Medicine, Ayurvedic; Memory Disorders; Mice; Nootropic Agents; Phytotherapy; Plant Extracts; Plant Roots; Scopolamine; Transfer, Psychology; Withania