withanoside-iv and Disease-Models--Animal

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

Although methylprednisolone is the clinically standard medication and almost the only therapy for spinal cord injury (SCI), its effect on functional recovery remains questionable. Transplantation strategies using sources such as neural stem cells and embryonic spinal cord still have some hurdles to overcome before practical applications become available. We therefore aimed to develop a practical medication for SCI. Per oral treatment with withanoside IV, which was previously shown to regenerate neuronal networks in the brain, improved locomotor functions in mice with SCI. In the spinal cord after SCI, axons were crushed in the white matter and gray matter, and central nervous system (CNS) myelin level decreased. In mice treated with withanoside IV (10micromol/kg body weight/day, for 21 days), axonal density and peripheral nervous system (PNS) myelin level increased. The loss of CNS myelin and increase in reactive gliosis were not affected by withanoside IV. These results suggest that oral administration of withanoside IV may ameliorate locomotor functions by facilitating both axonal regrowth and increase in PNS myelin level.

Topics: Analysis of Variance; Animals; Axons; Disease Models, Animal; Ergosterol; Exploratory Behavior; Lower Extremity; Male; Mice; Motor Activity; Myelin Proteins; Myelin Sheath; Nerve Regeneration; Neurofilament Proteins; Peripheral Nervous System; Recovery of Function; Spinal Cord Injuries; Time Factors