Naturally occurring conjugated octadecatrienoic acids are strong inhibitors of prostaglandin biosynthesis

Abstract

Fatty acids from natural sources (mostly seed oils) were isolated and assayed for their effect on the bioconversio of arachidonic acid into prostaglandin E 2, using sheep vesicular gland microsomes. Homologues and isomers of the naturally occurring fatty acids, obtained by chemical modification and/or organic synthetic methods, were also tested. Two very active cyclooxygenase inhibitors were discovered, namely jacarandic acid (8 Z , 10 E , 12 Z -octadecatrienoic acid), isolated from Jacarandaa mimosifolia , the concentration which gives 50% inhibition ([I] 50) being 2.4 μM and the synthetic 8 Z , 10 E , 12 E -octadecarienoic acid, having an [I] 50 of 1.0 μM. Under the conditions of the assay (75 μM substrate), earlier described potent inhibitors showed the following [I] 50′s: indomethacin: 1.3 μM; 9,12-octadecadiynoic acid: 1.3 μM, 8 Z , 12 E , 14 Z -eicosatrienoic acid: 2.7 μM; 5,8,11,14-eicosatetraynoic acid: 4.4 μM. At a concentration of about half that of the substrate, the following naturally occurring fatty acids revealed inhibition ([I] 50): columbinic acid (29 μM), calendulic acid (31 μM), liagoric acid (31 μM), ximenynic acid (39 μM), crepenynic acid (40 μM) and timnodonic acid (43 μM). Other fatty acids, and some of the above acids, were converted themselves more or less rapidly, mostly into conjugated monohydroxy fatty acids.