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

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-kappa B-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 (PGE(2)) and nuclear factor kappa B (NF-kappa B) 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, PGE(2) and NF-kappa B 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-kappa B-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.

Automated summary

This study investigates the anti-inflammatory mechanism of monoamine oxidase inhibitor (MAOI) in carrageenan-induced inflammation models and explores the role of the MAO-mediated H2O2-NF-kappa B-COX-2 pathway in acute inflammation. The results show that MAOI exhibits anti-inflammatory and H2O2 scavenging activities, reducing swelling, leukocyte extravasation, and the levels of COX-2, PGE(2), and NF-kappa B in inflamed tissue.