Withanoside IV and its active metabolite, sominone, attenuate Aβ(25–35)‐induced neurodegeneration

Kuboyama, Tomoharu; Tohda, Chihiro; Komatsu, Katsuko

doi:10.1111/j.1460-9568.2006.04664.x

Cited by 171Phytochemicals and Medicinal PlantsMedicinal Plants and NeuroprotectionAlzheimer's disease research and treatments

Withanoside IV and its active metabolite, sominone, attenuate Aβ(25–35)‐induced neurodegeneration

Kuboyama, Tomoharu, Tohda, Chihiro, Komatsu, Katsuko·2006·European Journal of Neuroscience

DOI 10.1111/j.1460-9568.2006.04664.x

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Abstract

At the present, medication of dementia is limited to symptomatic treatments such as the use of cholinesterase inhibitors. To cure dementia completely, that is regaining neuronal function, reconstruction of neuronal networks is necessary. Therefore, we have been exploring antidementia drugs based on reconstructing neuronal networks in the damaged brain and found that withanoside IV (a constituent of Ashwagandha; the root of Withania somnifera) induced neurite outgrowth in cultured rat cortical neurons. Oral administration of withanoside IV (10 micromol/kg/day) significantly improved memory deficits in Abeta(25-35)-injected (25 nmol, i.c.v.) mice and prevented loss of axons, dendrites, and synapses. Sominone, an aglycone of withanoside IV, was identified as the main metabolite after oral administration of withanoside IV. Sominone (1 microM) induced axonal and dendritic regeneration and synaptic reconstruction significantly in cultured rat cortical neurons damaged by 10 microM Abeta(25-35). These data suggest that orally administrated withanoside IV may ameliorate neuronal dysfunction in Alzheimer's disease and that the active principle after metabolism is sominone.

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Various CNS active Indian herbal medicines such as Withania somnifera, Centella asiatica, Celastrus paniculatus and Bacopa monnieri have shown cognitive improvement in experimental models of Alzheimer's disease when given as prophylactic treatment.
“Various CNS active Indian herbal medicines like Withania somnifera, Centella asiatica, Celastrus paniculatus and Bacopa monnieri have shown cognitive improvement in experimental models of AD when given as prophylactic treatment [43,44,45,46,47,48].”
From Indian Medicinal Herbs and Formulations for Alzheimer’s Disease, from Traditional Knowledge to Scientific Assessment (2020) · cites this paper as [44]
Withanoside IV (10 micromol/kg orally) prevented cognitive impairment in the experimental model of AD.
“Withanoside IV, another chemical constituent of Withania, when administered orally at the dose of 10 micromol/kg prevented cognitive impairment in the experimental model of AD [44].”
From Indian Medicinal Herbs and Formulations for Alzheimer’s Disease, from Traditional Knowledge to Scientific Assessment (2020) · cites this paper as [44]
Sominone (1 microM) induced axonal and dendritic regeneration and synaptic reconstruction in cultures of rat cortical neurons damaged by the amyloid peptide, Aβ(25-35).
“Sominone (1 microM) a metabolite of Withanoside IV, induced axonal and dendritic regeneration and synaptic reconstruction in cultures of rat cortical neurons damaged by the amyloid peptide, Aβ(25–35) [44].”
From Indian Medicinal Herbs and Formulations for Alzheimer’s Disease, from Traditional Knowledge to Scientific Assessment (2020) · cites this paper as [44]
Withaferin-A (1.882 microg per mouse) inhibits PMA-induced EPCR shedding by inhibition of TNF-alpha and IL-1b in HUVECs by inactivating TACE.
“Withaferin-A extracted from WS (1.882 µg per mouse) could inhibit phorbol-12-myristate 13-acetate (PMA)-induced [Endothelial protein C receptor (EPCR)] shedding by the inhibition of TNF-α and Interleukine (IL)-1b in Human Umbilical Vein Endothelial Cell lines (HUVECs) by inactivating tumor necrosis factor-α converting enzyme (TACE).”
From Withania somnifera (L.) Dunal (Ashwagandha): A comprehensive review on ethnopharmacology, pharmacotherapeutics, biomedicinal and toxicological aspects (2021) · cites this paper as [164]
Withaferin-A at 1.882 μg per mouse (I.V.) inhibits TNF-α and IL-1b.
“Inhibited TNF-α and IL-1b”
From Withania somnifera (L.) Dunal (Ashwagandha): A comprehensive review on ethnopharmacology, pharmacotherapeutics, biomedicinal and toxicological aspects (2021) · cites this paper as [164]

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Authors: Kuboyama, T., Tohda, C., & Komatsu, K.
Affiliations: University of Toyama (JP)
Corresponding author: Tohda, Chihiro
ORCID: Kuboyama, Tomoharu
Tohda, Chihiro
Komatsu, Katsuko
Venue: European Journal of Neuroscience
Publisher: Wiley
Published: 2006-03
Volume: 23
Issue: 6
Pages: 1417-1426
ISSN: 0953-816X (ISSN-L)
1460-9568
DOI: 10.1111/j.1460-9568.2006.04664.x
OpenAlex: W1841364166
Cited by: 171
References: 34
Citations by year: 2026: 9 · 2025: 11 · 2024: 10 · 2023: 13 · 2022: 12 · 2021: 13 · 2020: 15 · 2019: 6 · 2018: 7 · 2017: 11 · 2016: 8 · 2015: 11 · 2014: 5 · 2013: 3 · 2012: 5
FWCI: 15.77
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 15 d)
Locations: European Journal of Neuroscience (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
Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords: withanoside IV, amyloid beta 25-35, Alzheimer's disease, neurodegeneration, anti-dementia drugs, neurite outgrowth, axon regeneration, memory impairment, Withania somnifera, oral administration, cortical neurons
MeSH terms: Animals, Cerebral Cortex, Chromatography, High Pressure Liquid, Ergosterol, Immunohistochemistry, Male, Memory, Nerve Degeneration, Nerve Regeneration, Neurons, Peptide Fragments, Plant Extracts, Mass Spectrometry, Synapses, Amyloid beta-Peptides, Neurites, Rats, Sprague-Dawley, Maze Learning, Withania, Mice, Rats

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Withanoside IV and its active metabolite, sominone, attenuate Aβ(25–35)‐induced neurodegeneration

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