curcumin and cyclopentanone

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-hydroxy-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 Ca(2+) 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 histamine release induced by increased intracellular Ca(2+) concentrations in response to stimulants such as thapsigargin and ionomycin. These compounds also showed potent inhibitory effects on (45)Ca(2+) 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 Ca(2+) 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.

Topics: Animals; Benzylidene Compounds; Calcium; Cell Line, Tumor; Curcumin; Cyclopentanes; Dose-Response Relationship, Drug; Histamine Release; Mast Cells; Molecular Structure; Rats

Curcumin has been extensively studied for its anti-inflammatory activities. However, its potential beneficial effects on various disease preventions and treatments are limited by its unstable structure. The beta-diketone moiety renders curcumin to be rapidly metabolized by aldo-keto reductase in liver. In the present study, a series of curcumin analogues with more stable chemical structures were synthesized and several compounds showed an enhanced ability to inhibit lipopolysaccharide (LPS)-induced TNF-alpha and IL-6 synthesis in macrophages.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Cyclohexanones; Cyclopentanes; Interleukin-6; Lipopolysaccharides; Macrophages; Mice; Tumor Necrosis Factor-alpha