URSOLIC ACID FROM PLANTAGO-MAJOR, A SELECTIVE INHIBITOR OF CYCLOOXYGENASE-2 CATALYZED PROSTAGLANDIN BIOSYNTHESIS

A hexane extract of Plantago major was investigated by bioactivity-dir ected fractionation, using an in vitro cyclooxygenase-2 (COX-2) cataly zed prostaglandin biosynthesis inhibition assay, and resulted in the i solation of ursolic acid (1). This triterpenoid showed a significant C OX-2 inhibitory effect, directly on the enzyme activity, with an IC50 value of 130 mu M and a COX-2/COX-1 selectivity ratio of 0.6. The stru ctural isomer oleanolic acid (2) was found to be less active than 1, w ith an IC50 value of 296 mu M, but showed a similar selectivity ratio (0.8). Furthermore, no significant inhibition on COX-2 or COX-1 was ob served by the triterpenoid, 18 beta-glycyrrhetinic acid (3). The direc t inhibitory effect of 1 and 2 on COX-2 catalyzed prostaglandin biosyn thesis increased with preincubation, indicating a time-dependent inhib ition, while the effect on COX-1 was found to be independent of preinc ubation time.