Chamavioline—Antiedematous,but not a constituent of Matricaria recutita

The antiphlogistic and spasmolytic effects of Matricaria recutita L. (German chamomile) are due to the combination of constituents, most notably bisaboloids, flavonoids, proazulenes and azulenes. Chamavioline (7-ethyl-4-methyl-azulene-1-carbaldehyde, 1) was thought to be part of the latter group. After the unsuccessful search for chamavioline in chamomile of different provenances, we postulate that it is an artefact. We describe its three-step synthesis from 5-ethyl-2-methyl-pyridine. Chamavioline inhibited cyclooxygenase-2 (57% at 1 μM). The effect could not be increased by higher concentrations. It did not inhibit cyclooxygenase-1 up to a concentration of 10 μM. After topical application, it reduced the TPA-induced mouse ear edema statistically significantly 6 h after the induction of the edema by 23 and 30% in concentrations of 0.1 and 1.0 μmol/ear. The related azulenes chamazulene carboxylic acid (3), a constituent of chamomile, and the synthetic 4- and 6-azulene acetic acids inhibited the edema by 32, 41 and 46% at 1 μmol/ear. The appropriate time for the application of test compounds in this animal model was determined in exploratory experiments with 3.