Academic Journal
β-sitosterol reduces anxiety and synergizes with established anxiolytic drugs in mice
| العنوان: | β-sitosterol reduces anxiety and synergizes with established anxiolytic drugs in mice |
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| المؤلفون: | Panayotis, Nicolas, Freund, Philip, Marvaldi, Letizia, Shalit, Tali, Brandis, Alexander, Mehlman, Tevie, Tsoory, Michael, Fainzilber, Mike |
| المساهمون: | Weizmann Institute of Science Rehovot, Israël |
| المصدر: | ISSN: 2666-3791 ; Cell Reports Medicine ; https://hal.archives-ouvertes.fr/hal-03523050 ; Cell Reports Medicine, Cell Press, 2021, 2 (5), pp.100281. ⟨10.1016/j.xcrm.2021.100281⟩. |
| بيانات النشر: | HAL CCSD Cell Press |
| سنة النشر: | 2021 |
| المجموعة: | Archive ouverte HAL (Hyper Article en Ligne, CCSD - Centre pour la Communication Scientifique Directe) |
| مصطلحات موضوعية: | [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] |
| الوصف: | International audience ; 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 alpha5 mutant mouse model with reduced anxiety identifies the hypocholesterolemic agent beta-sitosterol as a promising candidate. Beta-sitosterol activity is validated by both intraperitoneal and oral application in mice, revealing it as the only clear anxiolytic from five closely related phytosterols. Beta-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 beta-sitosterol with the SSRI fluoxetine. These preclinical findings support further development of beta-sitosterol, either as a standalone anxiolytic or in combination with low-dose SSRIs. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | hal-03523050; https://hal.archives-ouvertes.fr/hal-03523050; https://hal.archives-ouvertes.fr/hal-03523050/document; https://hal.archives-ouvertes.fr/hal-03523050/file/mmc6%281%29.pdf |
| DOI: | 10.1016/j.xcrm.2021.100281 |
| الاتاحة: | https://hal.archives-ouvertes.fr/hal-03523050 https://hal.archives-ouvertes.fr/hal-03523050/document https://hal.archives-ouvertes.fr/hal-03523050/file/mmc6%281%29.pdf https://doi.org/10.1016/j.xcrm.2021.100281 |
| Rights: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.7A94A2C5 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.xcrm.2021.100281 |
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