Improved Pharmacokinetic Profile and Anti-Inflammatory Property of a Novel Curcumin Derivative, A50
Improved Pharmacokinetic Profile and Anti-Inflammatory Property of a Novel Curcumin Derivative, A50
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新型姜黄素衍生物 A50 的药代动力学特征和抗炎特性得到改善
DOI：
10.2174/1570180811310060010
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发表时间：
2013-07-01
影响因子：
1
通讯作者：
Wang, Yi
中科院分区：
文献类型：
--
作者：
Chen, Xiangjian;Ren, Luqing;Wang, Yi
过去十年的广泛研究支持姜黄素的抗炎特性。然而，由于姜黄素的β-二酮部分分解和酚性葡萄糖醛酸苷导致其不稳定性和不良的代谢特性，极大地限制了其开发和临床应用。本文设计并报道了一种不含β-二酮和酚羟基的姜黄素衍生物（A50）。X射线衍射分析表明，A50比姜黄素具有更刚性的结构。A50在大鼠体内的药代动力学研究表明，与姜黄素相比，其代谢参数显着改善。此外，A50通过抑制巨噬细胞中ERK和JNK磷酸化的机制，表现出比姜黄素更强的抗炎活性。这些结果表明，结构修饰是药代动力学和药理学上有益的，并且A50可能是治疗各种炎症性疾病的有希望的抗炎候选物。
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 beta-diketone moiety decomposition and phenolic glucuronides. In this paper, a curcumin derivative (A50) without beta-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.