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β-sitosterol reduces anxiety and synergizes with established anxiolytic drugs in mice
Anxiety and stress-related conditions represent a significant health burden in modern society. Unfortunately, most anxiolytic drugs are prone to side effects, limiting their long-term usage. Here, we employ a bioinformatics screen to identify drugs for repurposing as anxiolytics. Comparison of drug-...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149471/ https://www.ncbi.nlm.nih.gov/pubmed/34095883 http://dx.doi.org/10.1016/j.xcrm.2021.100281 |
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author | Panayotis, Nicolas Freund, Philip A. Marvaldi, Letizia Shalit, Tali Brandis, Alexander Mehlman, Tevie Tsoory, Michael M. Fainzilber, Mike |
author_facet | Panayotis, Nicolas Freund, Philip A. Marvaldi, Letizia Shalit, Tali Brandis, Alexander Mehlman, Tevie Tsoory, Michael M. Fainzilber, Mike |
author_sort | Panayotis, Nicolas |
collection | PubMed |
description | Anxiety and stress-related conditions represent a significant health burden in modern society. Unfortunately, most anxiolytic drugs are prone to side effects, limiting their long-term usage. Here, we employ a bioinformatics screen to identify drugs for repurposing as anxiolytics. Comparison of drug-induced gene-expression profiles with the hippocampal transcriptome of an importin α5 mutant mouse model with reduced anxiety identifies the hypocholesterolemic agent β-sitosterol as a promising candidate. β-sitosterol activity is validated by both intraperitoneal and oral application in mice, revealing it as the only clear anxiolytic from five closely related phytosterols. β-sitosterol injection reduces the effects of restraint stress, contextual fear memory, and c-Fos activation in the prefrontal cortex and dentate gyrus. Moreover, synergistic anxiolysis is observed when combining sub-efficacious doses of β-sitosterol with the SSRI fluoxetine. These preclinical findings support further development of β-sitosterol, either as a standalone anxiolytic or in combination with low-dose SSRIs. |
format | Online Article Text |
id | pubmed-8149471 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-81494712021-06-03 β-sitosterol reduces anxiety and synergizes with established anxiolytic drugs in mice Panayotis, Nicolas Freund, Philip A. Marvaldi, Letizia Shalit, Tali Brandis, Alexander Mehlman, Tevie Tsoory, Michael M. Fainzilber, Mike Cell Rep Med Report Anxiety and stress-related conditions represent a significant health burden in modern society. Unfortunately, most anxiolytic drugs are prone to side effects, limiting their long-term usage. Here, we employ a bioinformatics screen to identify drugs for repurposing as anxiolytics. Comparison of drug-induced gene-expression profiles with the hippocampal transcriptome of an importin α5 mutant mouse model with reduced anxiety identifies the hypocholesterolemic agent β-sitosterol as a promising candidate. β-sitosterol activity is validated by both intraperitoneal and oral application in mice, revealing it as the only clear anxiolytic from five closely related phytosterols. β-sitosterol injection reduces the effects of restraint stress, contextual fear memory, and c-Fos activation in the prefrontal cortex and dentate gyrus. Moreover, synergistic anxiolysis is observed when combining sub-efficacious doses of β-sitosterol with the SSRI fluoxetine. These preclinical findings support further development of β-sitosterol, either as a standalone anxiolytic or in combination with low-dose SSRIs. Elsevier 2021-05-18 /pmc/articles/PMC8149471/ /pubmed/34095883 http://dx.doi.org/10.1016/j.xcrm.2021.100281 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Report Panayotis, Nicolas Freund, Philip A. Marvaldi, Letizia Shalit, Tali Brandis, Alexander Mehlman, Tevie Tsoory, Michael M. Fainzilber, Mike β-sitosterol reduces anxiety and synergizes with established anxiolytic drugs in mice |
title | β-sitosterol reduces anxiety and synergizes with established anxiolytic drugs in mice |
title_full | β-sitosterol reduces anxiety and synergizes with established anxiolytic drugs in mice |
title_fullStr | β-sitosterol reduces anxiety and synergizes with established anxiolytic drugs in mice |
title_full_unstemmed | β-sitosterol reduces anxiety and synergizes with established anxiolytic drugs in mice |
title_short | β-sitosterol reduces anxiety and synergizes with established anxiolytic drugs in mice |
title_sort | β-sitosterol reduces anxiety and synergizes with established anxiolytic drugs in mice |
topic | Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149471/ https://www.ncbi.nlm.nih.gov/pubmed/34095883 http://dx.doi.org/10.1016/j.xcrm.2021.100281 |
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