Inhibition of 5-lipoxygenase activity by the natural anti-inflammatory compound aethiopinone

Objective and Design: We have investigated the mechanisms of action of aeth iopinone, an anti-inflammatory compound from Salvia aethiopis L, roots. Material and Subjects: Human neutrophils from healthy volunteers and murine peritoneal macrophages. Swiss mice were randomly divided into groups of si x animals. Treatment: Test compounds were applied topically in the mouse ea r oedema test. In the air pouch, mice received aethiopinone (0.001-0.5 mu m ol/pouch or 12.5-50 mg/kg p. o.). Methods: LTB4 production was assayed in human neutrophils and COX-2 and iNO S activities in murine macrophages. Air pouches were induced subcutaneously in mice and injected with zymosan on the day six. Mouse ear oedema was ind uced by arachidonic acid. Dunnett's t-test was employed for statistical ana lysis. Results: We have observed potent inhibitory effects on human neutrophil LTB 4 production without effects on COX or NOS activities. Aethiopinone is an i n vitro inhibitor of 5-LO from human neutrophils (IC50 = 0.11 muM) In addit ion, aethiopinone reduced leukocyte accumulation and showed in vivo inhibit ory activity on this enzyme. Conclusions: Our results indicate that inhibition of 5-LO could participate in the anti-inflammatory properties of this natural product.