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Neuritic regeneration and synaptic reconstruction induced by withanolide A
Open accessAbstract
We investigated whether withanolide A (WL-A), isolated from the Indian herbal drug Ashwagandha (root of Withania somnifera), could regenerate neurites and reconstruct synapses in severely damaged neurons. We also investigated the effect of WL-A on memory-deficient mice showing neuronal atrophy and synaptic loss in the brain. Axons, dendrites, presynapses, and postsynapses were visualized by immunostaining for phosphorylated neurofilament-H (NF-H), microtubule-associated protein 2 (MAP2), synaptophysin, and postsynaptic density-95 (PSD-95), respectively. Treatment with A beta(25-35) (10 microM) induced axonal and dendritic atrophy, and pre- and postsynaptic loss in cultured rat cortical neurons. Subsequent treatment with WL-A (1 microM) induced significant regeneration of both axons and dendrites, in addition to the reconstruction of pre- and postsynapses in the neurons. WL-A (10 micromol kg(-1) day(-1), for 13 days, p.o.) recovered A beta(25-35)-induced memory deficit in mice. At that time, the decline of axons, dendrites, and synapses in the cerebral cortex and hippocampus was almost recovered. WL-A is therefore an important candidate for the therapeutic treatment of neurodegenerative diseases, as it is able to reconstruct neuronal networks.
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Metadata
- Authors
- Kuboyama, T., Tohda, C., & Komatsu, K.
- Affiliations
- University of Toyama (JP)
- Institute of Natural Medicine, University of Toyama (JP)
- Corresponding author
- Komatsu, Katsuko
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2005-04
- Volume
- 144
- Issue
- 7
- Pages
- 961-971
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC1576076
- OpenAlex
- W2062620653
- Cited by
- 339
- References
- 45
- Citations by year
- 2026: 17 · 2025: 12 · 2024: 21 · 2023: 25 · 2022: 20 · 2021: 21 · 2020: 21 · 2019: 11 · 2018: 19 · 2017: 22 · 2016: 20 · 2015: 23 · 2014: 16 · 2013: 21 · 2012: 15
- FWCI
- 17.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Phytochemicals and Medicinal Plants
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- withanolide A, Withania somnifera, neurite regeneration, axonal atrophy, dendritic atrophy, synaptic loss, amyloid beta 25-35, memory impairment, neurodegenerative diseases, neurofilament H, synaptophysin, PSD-95, cortical neurons, hippocampus, neuroprotection
- MeSH terms
- Animals, Cells, Cultured, Female, Nerve Regeneration, Plant Extracts, Pregnancy, Synapses, Neurites, Rats, Sprague-Dawley, Plant Roots, Withania, Rats
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