Abstract
The present study aimed to evaluate the anti-inflammatory effects of ethanolic clove extract, ketorolac, and their combination in a formalin-induced paw inflammation model in rats. Thirty albinos Wistar rats were randomly divided into six groups, each group contained five rats: normal control, formalin control, low-dose clove extract, high-dose clove extract, ketorolac-treated, and ketorolac combined with clove extract. The added paw thickness measurements and of serum IL-1β level and IL-6 level and TNF-α level and PGE2 level were determined using ELISA Kits up to 24 h after formalin administration. The level of anti-inflammatory mediators in the formalin control groups was significantly (p < 0.05) high, indicating the successful induction of acute inflammation. The effects of ketorolac were significant, decreasing IL-6 and PGE2 levels in accordance with cyclooxygenase inhibition activity. Clove extract produced dose-dependent anti-inflammatory effects, especially decreasing IL-1β, and attaining a balance for PGE2, which may be at least partially due to eugenol-mediated inhibition of NF-κB signaling, and antioxidant effects. Ketorolac showed better early IL-1β suppression and alteration of some anti-inflammatory parameters when combined with clove extract compared to monotherapy. However, some rebound effects at later time points may indicate possible pharmacokinetic interactions and therefore dose optimization. These findings indicate that ethanolic clove extract possesses significant anti-inflammatory activity and may enhance the therapeutic efficacy of ketorolac when used in combination. Clove extract could serve as a promising natural adjunct to conventional NSAID therapy to improve efficacy and potentially reduce adverse effects.

Key words: Clove extract (Eugenol), Formalin-induced inflammation, Ketorolac, PGE2, Pro-inflammatory cytokines