Ursolic acid from Plantago major, a selective inhibitor of cyclooxygenase-2 catalyzed prostaglandin biosynthesis.
A hexane extract of Plantago major was investigated by bioactivity-directed fractionation, using an in vitro cyclooxygenase-2 (COX-2) catalyzed prostaglandin biosynthesis inhibition assay, and resulted in the isolation of ursolic acid (1). This triterpenoid showed a significant COX-2 inhibitory effect, directly on the enzyme activity, with an IC50 value of 130 microM and a COX-2/COX-1 selectivity ratio of 0.6. The structural isomer oleanolic acid (2) was found to be less active than 1, with an IC50 value of 295 microM, but showed a similar selectivity ratio (0.8). Furthermore, no significant inhibition on COX-2 or COX-1 was observed by the triterpenoid, 18beta-glycyrrhetinic acid (3). The direct inhibitory effect of 1 and 2 on COX-2 catalyzed prostaglandin biosynthesis increased with preincubation, indicating a time-dependent inhibition, while the effect on COX-1 was found to be independent of preincubation time.
Ringbom
T
T
Division of Pharmacognosy, Department of Pharmacy, Biomedical Centre, Uppsala University, Box 579, S-751 23 Uppsala, Sweden.
Segura
L
L
Noreen
Y
Y
Perera
P
P
Bohlin
L
L
D000818:Animals; D002417:Cattle; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology; D066298:In Vitro Techniques; D007527:Isoenzymes; D010943:Plantago / Q000737:chemistry*; D010946:Plants, Medicinal; D011451:Prostaglandin-Endoperoxide Synthases; D011453:Prostaglandins / Q000096:biosynthesis*; D012756:Sheep; D014315:Triterpenes / Q000302:isolation & purification* / Q000494:pharmacology; D000097245:Ursolic Acid
D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D011451:Prostaglandin-Endoperoxide Synthases; D011453:Prostaglandins; D014315:Triterpenes; D000097245:Ursolic Acid