ß-sitosterol reduces anxiety and synergizes with established anxiolytic drugs in mice.
Cell Rep Med
; 2(5): 100281, 2021 05 18.
Article
em En
| MEDLINE
| ID: mdl-34095883
ABSTRACT
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 ß-sitosterol as a promising candidate. ß-sitosterol activity is validated by both intraperitoneal and oral application in mice, revealing it as the only clear anxiolytic from five closely related phytosterols. ß-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 ß-sitosterol with the SSRI fluoxetine. These preclinical findings support further development of ß-sitosterol, either as a standalone anxiolytic or in combination with low-dose SSRIs.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ansiedade
/
Transtornos de Ansiedade
/
Sitosteroides
/
Ansiolíticos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article