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dc.contributor.authorZada, Wahid
dc.contributor.authorVanRyzin, Jonathan W
dc.contributor.authorPerez-Pouchoulen, Miguel
dc.contributor.authorBaglot, Samantha L
dc.contributor.authorHill, Matthew N
dc.contributor.authorAbbas, Ghulam
dc.contributor.authorClark, Sarah M
dc.contributor.authorRashid, Umer
dc.contributor.authorMcCarthy, Margaret M
dc.contributor.authorMannan, Abdul
dc.date.accessioned2022-08-30T14:07:02Z
dc.date.available2022-08-30T14:07:02Z
dc.date.issued2022-08-26
dc.identifier.urihttp://hdl.handle.net/10713/19643
dc.description.abstractModulation of the endocannabinoid system (ECS) is a novel putative target for therapeutic intervention in depressive disorders. Altering concentrations of one of the principal endocannabinoids, N-arachidonoylethanolamine, also known as anandamide (AEA) can affect depressive-like behaviors through several mechanisms including anti-inflammatory, hormonal, and neural circuit alterations. Recently, isoflavonoids, a class of plant-derived compounds, have been of therapeutic interest given their ability to modulate the metabolism of the endogenous ligands of the ECS. To determine the therapeutic potential of isoflavonoids, we screened several candidate compounds (Genistein, Biochanin-A, and 7-hydroxyflavone) in silico to determine their binding properties with fatty acid amide hydrolase (FAAH), the primary degrative enzyme for AEA. We further validated the ability of these compounds to inhibit FAAH and determined their effects on depressive-like and locomotor behaviors in the forced swim test (FST) and open field test in male and female mice. We found that while genistein was the most potent FAAH inhibitor, 7-hydroxyflavone was most effective at reducing immobility time in the forced swim test. Finally, we measured blood corticosterone and prefrontal cortex AEA concentrations following the forced swim test and found that all tested compounds decreased corticosterone and increased AEA, demonstrating that isoflavonoids are promising therapeutic targets as FAAH inhibitors.en_US
dc.description.urihttps://doi.org/10.1002/prp2.999en_US
dc.language.isoenen_US
dc.publisherBritish Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.en_US
dc.relationThe authors confirm that the data that support the findings of this study are available within the article and its supplementary materials.en_US
dc.relation.ispartofPharmacology Research & Perspectivesen_US
dc.rights© 2022 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.en_US
dc.subjectanxietyen_US
dc.subjectdepressionen_US
dc.subjectendocannabinoidsen_US
dc.titleFatty acid amide hydrolase inhibition and N-arachidonoylethanolamine modulation by isoflavonoids: A novel target for upcoming antidepressants.en_US
dc.typeArticleen_US
dc.identifier.doi10.1002/prp2.999
dc.identifier.pmid36029006
dc.source.journaltitlePharmacology research & perspectives
dc.source.volume10
dc.source.issue5
dc.source.beginpagee00999
dc.source.endpage
dc.source.countryUnited States
dc.source.countryUnited States


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