Inhibitory effects of helenalin and related compounds on 5-lipoxygenase and leukotriene C-4 synthase in human blood cells

The sesquiterpene lactone helenalin, which can be isolated from several pla nt species of the Asteraceae family, is a potent antiinflammatory and antin eoplastic agent. In agreement, alcohol extracts of these plants are used fo r local external treatment of inflammatory conditions. Since leukotrienes a re important mediators in inflammatory processes, the inhibitory effects of helenalin and some derivatives on leukotriene (LT) biosynthesis were studi ed. Treatment of human platelets with helenalin provoked irreversible inhib ition of LTC., synthase in a concentration- and time-dependent manner with an IC50 of 12 muM after a 60 min preincubation. 11 alpha ,13-Dihydrohelenal in acetate was less potent. Interestingly, individual donors could be divid ed into two distinct groups with respect to the efficacy of helenalin to su ppress platelet LTC, synthase. In human granulocytes, helenalin inhibited b oth the 5-lipoxygenase (IC50 9 muM after 60 min preincubation) and LTC4 syn thase in a concentration- and time-dependent fashion. In contrast, the drug was without effect on LTA(4) hydrolase. The GSH-containing adducts (2 beta -(S-glutathionyl)-2,3-dihydrohelenalin and 2 beta-(S-glutathionyl)-2,3,11 a lpha ,13-tetra hydrohelenalin acetate) did not significantly inhibit LTC, s ynthase. The present results indicate a mechanism for the anti-inflammatory effect of helenalin and related compounds. (C) 2001 Elsevier Science Inc. All rights reserved.