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dc.contributor.authorAhmad, Hammad
dc.contributor.authorRauf, Khalid
dc.contributor.authorZada, Wahid
dc.contributor.authorMcCarthy, Margaret
dc.contributor.authorAbbas, Ghulam
dc.contributor.authorAnwar, Fareeha
dc.contributor.authorShah, Abdul Jabbar
dc.date.accessioned2020-11-02T18:05:36Z
dc.date.available2020-11-02T18:05:36Z
dc.date.issued2020-10-14
dc.identifier.urihttp://hdl.handle.net/10713/13998
dc.description.abstractBackground: Fear, stress, and anxiety-like behaviors originate from traumatic events in life. Stress response is managed by endocannabinoids in the body by limiting the uncontrolled retrieval of aversive memories. Pharmacotherapy-modulating endocannabinoids, especially anandamide, presents a promising tool for treating anxiety disorders. Here, we investigated the effect of kaempferol, a flavonoid, in the extinction of fear related memories and associated anxiety-like behavior. Methods: The ability of kaempferol to inhibit fatty-acid amide hydrolase (FAAH, the enzyme that catabolizes anandamide) was assessed in vitro using an enzyme-linked immunosorbent assay (ELISA) kit. For animal studies (in vivo), the extinction learning was evaluated using contextual fear conditioning (CFC, a behavioral paradigm based on ability to learn and remember aversive stimuli). Furthermore, an elevated plus-maze (EPM) model was used for measuring anxiety-like behavior, while serum corticosterone served as a biochemical indicator of anxiety. Lastly, the interaction of kaempferol with FAAH enzyme was also assessed in silico (computational study). Results: Our data showed that kaempferol inhibited the FAAH enzyme with an IC50 value of 1 µM. In CFC, it reduced freezing behavior in rats. EPM data demonstrated anxiolytic activity as exhibited by enhanced number of entries and time spent in the open arm. No change in blood corticosterone levels was noted. Our computational study showed that Kaempferol interacted with the catalytic amino acids (SER241, PHE192, PHE381, and THR377) of FAAH enzyme Conclusion: Our study demonstrate that kaempferol facilitated the extinction of aversive memories along with a reduction of anxiety. The effect is mediated through the augmentation of endocannabinoids via the inhibition of FAAH enzyme.en_US
dc.description.urihttps://doi.org/10.3390/molecules25204683en_US
dc.language.isoenen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofMolecules (Basel, Switzerland)en_US
dc.subjectcontextual fear conditioningen_US
dc.subjectendocannabinoidsen_US
dc.subjectfatty-acid amide hydrolaseen_US
dc.subjectfear extinctionen_US
dc.subjectkaempferolen_US
dc.titleKaempferol Facilitated Extinction Learning in Contextual Fear Conditioned Rats via Inhibition of Fatty-Acid Amide Hydrolaseen_US
dc.typeArticleen_US
dc.identifier.doi10.3390/molecules25204683
dc.identifier.pmid33066366
dc.source.volume25
dc.source.issue20
dc.source.countrySwitzerland


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