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

• Published in: Inflammopharmacology Vol. 31; no. 3; p. 1305
• Main Authors: Sur, Debjeet, Mondal, Chaitali, Balaraman, Ashok Kumar, Haldar, Pallab Kanti, Maji, Himangshu Sekhar, Bala, Asis
• Format: Journal Article
• Language: English
• Published: Switzerland 01-06-2023
• Subjects: Animals; Anti-Inflammatory Agents - therapeutic use; Carrageenan - pharmacology; Cyclooxygenase 2 - metabolism; Edema - metabolism; Humans; Hydrogen Peroxide - metabolism; Inflammation - metabolism; Mice; Monoamine Oxidase - metabolism; Monoamine Oxidase - pharmacology; Monoamine Oxidase - therapeutic use; Monoamine Oxidase Inhibitors - adverse effects; NF-kappa B - metabolism; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - metabolism; Signal Transduction; NF-κB; Monoamine oxidase; COX-2; Inflammation; Carrageenan-induced paw edema; Monoamine oxidase inhibitor
• ISSN: 1568-5608

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 H
O
-NF-κB-COX-2 pathway in acute inflammation.
In vitro anti-inflammatory activity and hydrogen peroxide (H
O
) 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 (PGE
) 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.
In vitro anti-inflammatory evaluations revealed the potential role of MAOI to inhibit heat-induced protein denaturation and human red cell membrane destabilization. H
O
inhibition activity of MAOI also proved their powerful role as an H
O
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, PGE
and NF-κB in inflamed tissue.
In short, this study demonstrates that inhibition of H
O
by MAOI alleviates CARR-induced paw edema possibly by inhibiting the H
O
-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.