EUGENOL - A DUAL INHIBITOR OF PLATELET-ACTIVATING-FACTOR AND ARACHIDONIC-ACID METABOLISM

Eugenol is an active principal and responsible for several pharmacolog ical activities of clove oil. We studied the effects of eugenol on hum an platelet aggregation, arachidonic acid (AA) and platelet-activating factor (PAF) metabolism and in vivo effects on AA and PAF-induced sho ck in rabbits. Eugenol strongly inhibited PAF-induced platelet aggrega tion with lesser effect against AA and collegen. The IC50 values were against AA: 31 +/- 0.5; collagen: 64 +/- 0.7 and PAF 7 +/- 0.2 mu M (n =9) respectively. In addition, eugenol stimulated PAF-acetylhydrolase activity suggesting that inhibition of PAF could be due to its inactiv ation to lyso-PAF. Pretreatment of rabbits with eugenol (50-100 mg/kg) prevented the lethal effects of intravenous PAF (11 mu g/kg) or AA (2 mg/kg) in a dose-dependent fashion. The protective effects of eugenol in the rabbits, however, were more pronounced against PAF-induced mor tality (100% protection). In addition, eugenol also inhibited AA metab olism via cyclooxygenase and lipoxygenase pathways in human platelets. Both the production of thromboxane-Az and 12-hydroxy-eicosatetraenoic acid was inhibited by eugenol in a concentration-related manner (30-1 20 mu M). In vivo, eugenol (50-100 mg/kg; i.p.) inhibited carrageenan- induced rat paw oedema (P < 0.001). In this test, eugenol was 5 times more potent than aspirin. These results provide evidence that eugenol acts as a dual antagonist of AA and PAF.