Abstract

Extensive researches within the last decade have supported the anti-inflammatory properties of curcumin. However, the development and clinical application of curcumin have been limited significantly by its instability and poor metabolic property resulting from the β-diketone moiety decomposition and phenolic glucuronides. In this paper, a curcumin derivative (A50) without β-diketone and phenolic hydroxyl groups was designed and reported. The X-ray diffraction analysis showed a more rigid structure of A50 than that of curcumin. A pharmacokinetic study of A50 in rats indicated that its metabolic parameters were significantly improved compared to those of curcumin. Furthermore, A50 exhibited stronger anti-inflammatory activity than curcumin did via the mechanism, at least partly, associated with inhibiting ERK and JNK phosphorylation in macrophages. These results suggest that the structural modification is both pharmacokinetically and pharmacologically beneficial, and A50 may be a promising anti-inflammatory candidate to treat various inflammatory diseases.

Keywords: Anti-inflammatory property, Curcumin, Crystal structure, (2E, 5E)-2, 5-bis(2, 5-dimethylbenzylidene) cyclopentanone, Mono-carbonyl analogue of curcumin, Pharmacokinetic profile.