Effects of benzylidenecyclopentanone analogues of curcumin on histamine release from mast cells

Abstract

Curcumin reportedly has anti-allergic effects and can inhibit the release of histamine from mast cells. In the present study, fourteen benzylidenecyclopentanone analogues of curcumin were studied for their effects on histamine release from rat basophilic leukemia (RBL-2H3) cells. After screening, four selected compounds: 2,5-bis- (4-hydroxybenzylidene) cyclopentanone; 2,5-bis(4-hydroxy-3-methoxybenzylidene)cyclopentanone; 2,5-bis(4-hy- droxy-3,5-dimethylbenzylidene) cyclopentanone; and 2,5-bis(4-hydroxy-3,5-diethylbenzylidene)cyclopentanone were studied for their concentration-dependent effects on histamine release and Ca2+ uptake. In RBL-2H3 cells and rat peritoneal mast cells stimulated with antigen or compound 48/80, respectively, the methoxy-hydroxy analogue was more potent than curcumin in inhibiting histamine release. In contrast, the inhibitory effects of methyl/ethyl analogues were less potent than those of curcumin. Moreover, these compounds abrogated hista- mine release induced by increased intracellular Ca2+ concentrations in response to stimulants such as thapsigar- gin and ionomycin. These compounds also showed potent inhibitory effects on 45Ca2+ uptake in RBL-2H3 cells. The mechanism of the inhibitory effects of these curcumin analogues on histamine release appeared to be related to blockade of Ca2+ signaling events. These results provide useful information to guide the development of new synthetic compounds for the treatment of allergic and inflammatory diseases related to histamine or mast cells. © 2009 Pharmaceutical Society of Japan.