In vivo activity of pseudoguaianolide sesquiterpene lactones in acute and chronic inflammation

The pseudoguaianolide sesquiterpene lactones 4-alpha-O-acetyl-pseudoguaian- 6 beta-olide (?), hymenin (2), ambrosanolide (3), tetraneurin A (4), parthe nin (5), hysterin (6) and confertdiolide O were evaluated for their ability to affect the inflammation responses induced by different agents. All the compounds showed activity against the 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced mouse ear edema. The ethyl phenylpropiolate (EPP)-induced mou se ear edema was inhibited by compounds 3, 5 and 7. However, when sesquiter pene lactones were assayed on the arachidonic acid (AA)-induced mouse ear e dema, none of them were active. The only sesquiterpene lactone orally activ e against the paw mouse edema induced by carrageenan was 7, which gave a 46 % edema inhibition after 3 h. On the other hand, compounds 3, 5 and 7 reduc ed the serotonin-induced paw edema in mice, although compound 7 was inactiv e in presence of cycloheximide. In addition, the sesquiterpene lactones wer e assayed against the chronic inflammation induced by repeated application of TPA on mouse ear. Confertdiolide was the most active compound; it reduce d the edema by 87% and had a more moderate effect against the leukocyte rec ruitment (36% reduction in myeloperoxidase (MPO) levels). A histological st udy of ear the samples treated with 7 presented no detectable morphological lesions such as those treated with dexamethasone. On the oxazolone-induced delayed type hypersensitivity (DTH) only compounds 4 and 5 were active 24 h after the challenge. Compound 5 affected polymorphonuclear leukocyte infi ltration (69% reduction in MPO levels). The results suggest that the especi al chemical structure and spatial conformation of confertdiolide may facili tate its anti-inflammatory effect.