Sominone enhances neurite outgrowth and spatial memory mediated by the neurotrophic factor receptor, RET
Open accessAbstract
BACKGROUND AND PURPOSE: Orally administered withanoside IV (a compound isolated from the roots of Withania somnifera) improved memory deficits in mice with a model of Alzheimer's disease induced by the amyloid peptide Abeta(25-35). Sominone, an aglycone of withanoside IV, was identified as an active metabolite after oral administration of withanoside IV. We aimed to identify receptors or associated molecules of sominone, and to investigate the effects of sominone on memory in normal mice. EXPERIMENTAL APPROACH: Phosphorylation levels of 71 molecules were compared between control and sominone-stimulated cortical cultured cells to search for target molecules of sominone. Object location memory and neurite density in the brain were evaluated in sominone-injected mice. KEY RESULTS: Phosphorylation of RET (a receptor for the glial cell line-derived neurotrophic factor, GDNF) was increased in neurons by sominone, without affecting the synthesis and secretion of GDNF. Knockdown of RET prevented sominone-induced outgrowths of axons and dendrites. After a single i.p. injection of sominone into normal mice, they could better memorize scenery information than control mice. Sixty minutes after sominone injection, RET phosphorylation was increased, particularly in the hippocampus of mice. After the memory tests, the densities of axons and dendrites were increased in the hippocampus by sominone administration. CONCLUSIONS AND IMPLICATIONS: Sominone could reinforce the morphological plasticity of neurons by activation of the RET pathway and thus enhance memory. Sominone, a compound with low molecular weight, may be a GDNF-independent stimulator of the RET pathway and/or a novel modulator of RET signalling.
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Methanolic root extract of W. somnifera dose dependently enhanced in-vitro dendrite formation in human neuroblastoma cells.
“Methanolic root extract dose dependently enhanced in-vitro dendrite formation in human neuroblastoma cells [159].”
From Indian Medicinal Herbs and Formulations for Alzheimer’s Disease, from Traditional Knowledge to Scientific Assessment (2020) · cites this paper as [159]
The enhancement of spatial memory by sominone may be attributed to neuritic outgrowth, which is mediated by the neurotrophic factor receptor, RET.
“The enhancement of spatial memory by sominone may be attributed to neuritic outgrowth, which is mediated by the neurotrophic factor receptor, RET [159].”
From Indian Medicinal Herbs and Formulations for Alzheimer’s Disease, from Traditional Knowledge to Scientific Assessment (2020) · cites this paper as [159]
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- Authors
- Tohda, C., & Joyashiki, E.
- Affiliations
- University of Toyama (JP)
- Corresponding author
- Tohda, Chihiro
- ORCID
- Tohda, Chihiro
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2009-07-29
- Volume
- 157
- Issue
- 8
- Pages
- 1427-1440
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC2765306
- OpenAlex
- W1974115839
- Cited by
- 62
- References
- 43
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 6 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 9 · 2018: 3 · 2017: 9 · 2016: 4 · 2015: 1 · 2014: 5 · 2013: 2 · 2012: 3
- FWCI
- 7.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (17500249)
- 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
- RET receptor, glial cell line-derived neurotrophic factor, withanoside IV, Withania somnifera, spatial memory, object location memory, neurite outgrowth, hippocampus, RET phosphorylation, memory enhancement
- MeSH terms
- Animals, Animals, Newborn, Axons, Cells, Cultured, Cerebral Cortex, Dehydroepiandrosterone, Dendrites, Ergosterol, Hippocampus, Male, Memory, Mice, Inbred Strains, Phosphorylation, Spatial Behavior, Neurites, Rats, Sprague-Dawley, Proto-Oncogene Proteins c-ret, Glial Cell Line-Derived Neurotrophic Factor, Mice, Rats
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