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Apigenin attenuates depressive-like behavior via modulating monoamine oxidase A enzyme activity in chronically stressed mice

Chronic stress is a risk factor for depression and is characterized by elevated levels of brain monoamine oxidase A (MAOA). Mounting evidence has shown that MAOA is a biochemical link between stress and depression. Apigenin (API), a natural flavonoid, as demonstrated in vitro inhibitory effect on MA...

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Autores principales: Olayinka, Juliet N., Akawa, Oluwole B., Ogbu, Emmanuela K., Eduviere, Anthony T., Ozolua, Raymond I., Soliman, Mahmoud
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10368777/
https://www.ncbi.nlm.nih.gov/pubmed/37501771
http://dx.doi.org/10.1016/j.crphar.2023.100161
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author Olayinka, Juliet N.
Akawa, Oluwole B.
Ogbu, Emmanuela K.
Eduviere, Anthony T.
Ozolua, Raymond I.
Soliman, Mahmoud
author_facet Olayinka, Juliet N.
Akawa, Oluwole B.
Ogbu, Emmanuela K.
Eduviere, Anthony T.
Ozolua, Raymond I.
Soliman, Mahmoud
author_sort Olayinka, Juliet N.
collection PubMed
description Chronic stress is a risk factor for depression and is characterized by elevated levels of brain monoamine oxidase A (MAOA). Mounting evidence has shown that MAOA is a biochemical link between stress and depression. Apigenin (API), a natural flavonoid, as demonstrated in vitro inhibitory effect on MAOA, is suggestive of antidepressant-like activity. However, the in vivo inhibitory effect of API on MAOA and how it affects depression still remain unclear. Here, we report the probable mechanisms of action of API in chronic unpredictable mild stress (CUMS)-induced depression in mice. Treatment with API reversed anhedonia, and reduced anxiety and immobility time in behavioral studies. API reduced brain corticosterone and malondialdehyde (MDA) levels but increased brain levels of glutathione and superoxide dismutase. Furthermore, interleukin-6 and tumor necrosis factor-α were attenuated by API. It also restored cell loss and inhibited the activity of MAOA in the hippocampal brain regions and prefrontal cortex. Comparative binding affinity of API for MAOA (-7.7 kcal/mol) through molecular docking studies was greater than that of reference compound, clorgyline (-6.8 kcal/mol). Favorable hydrophobic interactions important to API binding at MAOA binding cavity was revealed to include conventional hydrogen bond (Cys323 and Tyr444), π-Sulfur (Cys323), π-π Stacked (Tyr407), π-π T-shaped (Phe208), π-lone pair and π-alkyl (Ile335, Ile180) interactions. These results suggest that API is a potent, selective, reversible inhibitor of MAOA with capability of attenuating CUMS-induced depression via inhibiting MAOA enzyme activity and altering other pathomechanisms.
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spelling pubmed-103687772023-07-27 Apigenin attenuates depressive-like behavior via modulating monoamine oxidase A enzyme activity in chronically stressed mice Olayinka, Juliet N. Akawa, Oluwole B. Ogbu, Emmanuela K. Eduviere, Anthony T. Ozolua, Raymond I. Soliman, Mahmoud Curr Res Pharmacol Drug Discov Article Chronic stress is a risk factor for depression and is characterized by elevated levels of brain monoamine oxidase A (MAOA). Mounting evidence has shown that MAOA is a biochemical link between stress and depression. Apigenin (API), a natural flavonoid, as demonstrated in vitro inhibitory effect on MAOA, is suggestive of antidepressant-like activity. However, the in vivo inhibitory effect of API on MAOA and how it affects depression still remain unclear. Here, we report the probable mechanisms of action of API in chronic unpredictable mild stress (CUMS)-induced depression in mice. Treatment with API reversed anhedonia, and reduced anxiety and immobility time in behavioral studies. API reduced brain corticosterone and malondialdehyde (MDA) levels but increased brain levels of glutathione and superoxide dismutase. Furthermore, interleukin-6 and tumor necrosis factor-α were attenuated by API. It also restored cell loss and inhibited the activity of MAOA in the hippocampal brain regions and prefrontal cortex. Comparative binding affinity of API for MAOA (-7.7 kcal/mol) through molecular docking studies was greater than that of reference compound, clorgyline (-6.8 kcal/mol). Favorable hydrophobic interactions important to API binding at MAOA binding cavity was revealed to include conventional hydrogen bond (Cys323 and Tyr444), π-Sulfur (Cys323), π-π Stacked (Tyr407), π-π T-shaped (Phe208), π-lone pair and π-alkyl (Ile335, Ile180) interactions. These results suggest that API is a potent, selective, reversible inhibitor of MAOA with capability of attenuating CUMS-induced depression via inhibiting MAOA enzyme activity and altering other pathomechanisms. Elsevier 2023-07-11 /pmc/articles/PMC10368777/ /pubmed/37501771 http://dx.doi.org/10.1016/j.crphar.2023.100161 Text en © 2023 The Authors. Published by Elsevier B.V. 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 Article
Olayinka, Juliet N.
Akawa, Oluwole B.
Ogbu, Emmanuela K.
Eduviere, Anthony T.
Ozolua, Raymond I.
Soliman, Mahmoud
Apigenin attenuates depressive-like behavior via modulating monoamine oxidase A enzyme activity in chronically stressed mice
title Apigenin attenuates depressive-like behavior via modulating monoamine oxidase A enzyme activity in chronically stressed mice
title_full Apigenin attenuates depressive-like behavior via modulating monoamine oxidase A enzyme activity in chronically stressed mice
title_fullStr Apigenin attenuates depressive-like behavior via modulating monoamine oxidase A enzyme activity in chronically stressed mice
title_full_unstemmed Apigenin attenuates depressive-like behavior via modulating monoamine oxidase A enzyme activity in chronically stressed mice
title_short Apigenin attenuates depressive-like behavior via modulating monoamine oxidase A enzyme activity in chronically stressed mice
title_sort apigenin attenuates depressive-like behavior via modulating monoamine oxidase a enzyme activity in chronically stressed mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10368777/
https://www.ncbi.nlm.nih.gov/pubmed/37501771
http://dx.doi.org/10.1016/j.crphar.2023.100161
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