Oleuropein modulates anti-inflammatory activity of celecoxib and ketoprofen through cyclooxygenase pathway: in vivo, in silico and pharmacokinetics approaches.

Oleuropein (OLP), a bioactive compound mainly found in olive leaves, is recognized for its wide range of biological effects, such as antioxidant, anti-inflammatory, and antimicrobial activities. This study aimed to assess the anti-inflammatory effects of OLP in an in vivo model and explore its molecular interactions through in silico docking studies. We investigated the individual and combined effects of OLP (10 and 20 mg/kg) alongside standard anti-inflammatory drugs, celecoxib (CXB) and ketoprofen (KPN), at 42 mg/kg (p.o.) in a formalin-induced inflammatory chick model. In addition, an in silico analysis was conducted to examine how OLP and the standard drugs interact with cyclooxygenase (COX)-1 and COX-2 enzymes. The results indicated that OLP exhibited a dose-dependent anti-inflammatory effect in chicks, with OLP-20 mg/kg significantly reducing paw-licking frequency and paw edema diameters. Furthermore, the combination of OLP-20 mg/kg with CXB-42 mg/kg and KPN-42 mg/kg showed enhanced anti-inflammatory efficacy. In the molecular docking analysis, OLP demonstrated comparable binding interactions with both COX-1 (‒7.6 kcal/mol) and COX-2 (‒7.7 kcal/mol) enzymes, similar to the standard drugs. Pharmacokinetic (PK) analysis revealed that OLP has favorable properties and a safe toxicity profile, with an LD of 2000 mg/kg. In conclusion, OLP effectively and dose-dependently reduced paw licks and edema in animals, suggesting that its anti-inflammatory effects are mediated through interactions with COX-1 and COX-2 enzymes. Additional research is essential to comprehensively uncover the underlying mechanisms of its action and evaluate its potential for clinical use.