ABSTRACT: Roots and stem-bark of Mahonia aquifolium (Oregon grape) (Berberidaceae) are effectively used in the treatment of skin inflammatory conditions.In the present study, the effect of Mahonia aquifolium crude extract and its two representative alkaloid fractions containing protoberberine and bisbenzylisoquinoline (BBIQ) alkaloids on activity of 12-lipoxygenase (12-LOX), was studied. The reactivity with 1,1-diphenyl-2-picryl-hydrazyl (DPPH), a free stable radical, was evaluated to elucidate the rate of possible lipid-derived radical scavenging in the mechanism of the enzyme inhibition.The results indicate that although the direct radical scavenging mechanism cannot be ruled out in the lipoxygenase inhibition by Mahonia aquifolium and its constituents, other mechanisms based on specific interaction between enzyme and alkaloids could play the critical role in the lipoxygenase inhibition rather than non-specific reactivity with free radicals.