Topical anti-inflammatory agents from the alpine flavouring plant Artemisia umbelliformis Lam.

Abstract

Artemisia umbelliformis Lam. (Asteraceae) is an alpine flavouring plant used to produce the bitter liqueur genepy. The lipophilic flavonoid eupatilin, a series of sesquiterpenes lactones and the sesterpene lactone genepolide, isolated from this plant [1,2], were investigated for their topical anti-inflammatory activity (inhibition of the Croton oil-induced mouse ear dermatitis) in comparison to the steroidal and non steroidal anti-inflammatory drugs hydrocortisone and indomethacin [3]. Six hours after dermatitis induction, the anti-oedema potency of eupatilin was comparable to that of indomethacin (ID50=0.30 and 0.26µmol/cm2), and only one order of magnitude lower than that of hydrocortisone (ID50=0.03µmol/cm2). A slightly lower effect was observed for genepolide and the sesquiterpenes anhydroverlotorin, santamarin, 5-deoxy-5-hydroperoxy-telekin, 5-deoxy-5-hydroperoxy-epitelekin and costunolide (ID50 ranged from 0.35 to 0.73µmol/cm2), the most active being anhydroverlotorin and genepolide (ID50=0.35 and 0.40µmol/cm2). The overall effect of eupatilin (0.3µmol/cm2), anhydroverlotorin (0.4µmol/cm2) and genepolide (0.4µmol/cm2) on oedema development up to 48h was intermediate between those of equimolar doses of indomethacin and hydrocortisone at one order of magnitude lower doses, but their activity profile was similar to the latter. Eupatilin reduced also the leukocytes infiltrate in the ear tissue, similarly to the reference drugs. The effect of anhydroverlotorin and genepolide on inflammatory cells infiltration will also be discussed.