Perindopril Alleviates Inflammation via Cyclooxygenase Inhibition: A Bioinformatics, in vitro and in vivo Evaluation

Abstract

Background and Objective: Perindopril (PER), an angiotensin-converting enzyme (ACE) inhibitor with anti-apoptotic, antioxidant and anti-inflammatory characteristics, has long been used to treat cardiovascular illnesses.In this study, the enzyme inhibitory activity of PER against Cyclooxygenase-1 (COX-1) and Cyclooxygenase-2 (COX-2) was determined.Materials and Methods: The PERʼs anti-inflammatory actions were estimated by in vitro COX-1 and COX-2 inhibition assays, the in vivo rat model of carrageenan-induced paw edema, histopathological examination, molecular modeling, docking and molecular dynamics studies.The data were analyzed using the Analysis of Variance (ANOVA) Test.Results: The PER IC 50 values for COX-1 and COX-2 were calculated to be 8.3 and 0.1 µM, respectively, showing that PER has an 85.5-fold higher affinity for COX-2 than for COX-1.The PER was found to be a moderate inflammation suppressor in rat paw assay, comparable to celecoxib and indomethacin.Docking and molecular dynamics (MD) simulation supported the stable binding of PER with COX-2.Conclusion: Current findings revealed that PER can be used for local acute inflammation and utilized as a substitute for other topical anti-inflammatory medicines, particularly those containing steroids.