Neuritic regeneration and synaptic reconstruction induced by withanolide A

Kuboyama, Tomoharu; Tohda, Chihiro; Komatsu, Katsuko

doi:10.1038/sj.bjp.0706122

Cited by 339Phytochemicals and Medicinal PlantsMedicinal Plants and NeuroprotectionNerve injury and regeneration

Neuritic regeneration and synaptic reconstruction induced by withanolide A

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Kuboyama, Tomoharu, Tohda, Chihiro, Komatsu, Katsuko·2005·British Journal of Pharmacology

DOI 10.1038/sj.bjp.0706122PMC PMC1576076

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Abstract

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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The ameliorative outcomes of withanolide A were retained after treatment discontinuation.
“Additionally, the ameliorative outcomes were retained after treatment discontinuation [89].”
From The Multifaceted Role of Neuroprotective Plants in Alzheimer’s Disease Treatment (2022) · cites this paper as [89]

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Authors: Kuboyama, T., Tohda, C., & Komatsu, K.
Affiliations: University of Toyama (JP)
Institute of Natural Medicine, University of Toyama (JP)
Corresponding author: Komatsu, Katsuko
ORCID: Kuboyama, Tomoharu
Tohda, Chihiro
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
DOI: 10.1038/sj.bjp.0706122
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
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 1399 d)
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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Neuritic regeneration and synaptic reconstruction induced by withanolide A

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