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Inflammopharmacology

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24-02-2023 | Edema | Original Article

Attenuation of COX-2 enzyme by modulating H₂O₂-mediated NF-κB signaling pathway by monoamine oxidase inhibitor (MAOI): a further study on the reprofiling of MAOI in acute inflammation

Authors: Debjeet Sur, Chaitali Mondal, Ashok Kumar Balaraman, Pallab Kanti Haldar, Himangshu Sekhar Maji, Asis Bala

Published in: Inflammopharmacology | Issue 3/2023

Abstract

Objective

This study aims to investigate the anti-inflammatory mechanism of monoamine oxidase inhibitor (MAOI) in carrageenan (CARR) induced inflammation models to reprofile their use. We also aimed to explore the role of monoamine oxidase (MAO)-mediated H₂O₂–NF–κB–COX-2 pathway in acute inflammation.

Methods

In vitro anti-inflammatory activity and hydrogen peroxide (H₂O₂) scavenging activity were performed according to the established procedure. Inflammation was induced using CARR in BALB/c mice at the foot paw and peritoneal cavity. Hourly measurement of paw swelling was performed. The level of nitric oxide (NO), myeloperoxidase (MPO), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE₂) and nuclear factor κB (NF-κB) was determined using enzyme-linked immunosorbent assay (ELISA). Peritoneal fluid was collected to investigate total count, differential count of leukocytes, and capillary permeability.

Results

In vitro anti-inflammatory evaluations revealed the potential role of MAOI to inhibit heat-induced protein denaturation and human red cell membrane destabilization. H₂O₂ inhibition activity of MAOI also proved their powerful role as an H₂O₂ scavenger. Treatment with MAOI in CARR-induced mice significantly reduced paw edema, leukocyte extravasation, and total and differential leukocyte count. The result of ELISA showed MAOI effectively reduce the level of COX-2, PGE₂ and NF-κB in inflamed tissue.

Conclusions

In short, this study demonstrates that inhibition of H₂O₂ by MAOI alleviates CARR-induced paw edema possibly by inhibiting the H₂O₂-mediated NF-κB–COX-2 pathway. The present investigation identifies MAOI might reprofile for the treatment of acute inflammation also, the MAO enzyme may use as a novel therapeutic target to design and develop new class of anti-inflammatory agents.

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Title: Attenuation of COX-2 enzyme by modulating H2O2-mediated NF-κB signaling pathway by monoamine oxidase inhibitor (MAOI): a further study on the reprofiling of MAOI in acute inflammation
Authors: Debjeet Sur
Chaitali Mondal
Ashok Kumar Balaraman
Pallab Kanti Haldar
Himangshu Sekhar Maji
Asis Bala
Publication date: 24-02-2023
Publisher: Springer International Publishing
Keywords: Edema
Selegiline
Published in: Inflammopharmacology / Issue 3/2023
Print ISSN: 0925-4692
Electronic ISSN: 1568-5608
DOI: https://doi.org/10.1007/s10787-023-01165-5

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Attenuation of COX-2 enzyme by modulating H₂O₂-mediated NF-κB signaling pathway by monoamine oxidase inhibitor (MAOI): a further study on the reprofiling of MAOI in acute inflammation

Abstract

Objective

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Methods

Results

Conclusions

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