Dimethoxycurcumin, a Synthetic Curcumin Analogue, Induces Heme Oxygenase-1 Expression through Nrf2 Activation in RAW264.7 Macrophages.

Dimethoxycurcumin, a Synthetic Curcumin Analogue, Induces Heme Oxygenase-1 Expression through Nrf2 Activation in RAW264.7 Macrophages.
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DOI:
10.3164/jcbn.08-194
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发表时间:
2009-01
影响因子:
2.4
通讯作者:
Pae, Hyun-Ock
Pae, Hyun-Ock
中科院分区:
医学4区
文献类型:
--
作者:
Jeong, Sun-Oh;Oh, Gi-Su;Ha, Hun-Yong;Koo, Bon Soon;Kim, Hak Sung;Kim, Youn-Chul;Kim, Eun-Cheol;Lee, Kang-Min;Chung, Hun-Taeg;Pae, Hyun-Ock

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姜黄素[1,7-双(4-羟基-3-甲氧基苯基)-1,6-庚二酮-3,5-二酮]通过激活核因子-红细胞2相关因子2(Nrf 2)诱导血红素加氧酶-1(HO-1)表达,而姜黄素体内代谢产物之一四氢姜黄素[1,7-双(4-羟基-3-甲氧基苯基)-3,5-庚二酮]对HO-1表达和Nrf 2激活没有影响。本研究的目的是研究二甲氧基姜黄素[1,7-双(4,3-二甲氧基苯基)-1,6-庚烯-3,5-二酮](一种比姜黄素具有更高代谢稳定性的合成姜黄素类似物)是否能诱导RAW 264. 7巨噬细胞中HO-1表达达到与姜黄素相同的程度。二甲氧基姜黄素和姜黄素,但不是四氢姜黄素,诱导HO-1表达和Nrf 2核转位,这表明化合物的二芳基庚烷链的不饱和性质是至关重要的HO-1表达和Nrf 2激活。通过小干扰RNA阻断Nrf 2的合成,通过二甲氧基姜黄素阻断HO-1的表达,表明二甲氧基姜黄素可能通过Nrf 2激活诱导HO-1的表达。相比之下,二甲氧基姜黄素和姜黄素对HO-1表达具有大致相同的作用,表明二甲氧基姜黄素保留了其母体化合物姜黄素在RAW 264.7巨噬细胞中的HO-1诱导活性。
Curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] induces heme oxygenase-1 (HO-1) expression via activation of the nuclear factor-erythroid-2-related factor 2 (Nrf2), whereas tetrahydrocurcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-3,5-heptanedione], one of curcumin in vivo metabolites, has no effect on HO-1 expression and Nrf2 activation. The aim of this study was to investigate whether dimethoxycurcumin [1,7-bis(4,3-dimethoxyphenyl)-1,6-heptadiene-3,5-dione], a synthetic curcumin analogue with higher metabolic stability over curcumin, could induce HO-1 expression to the same extent as curcumin in RAW264.7 macrophages. Dimethoxycurcumin and curcumin, but not tetrahydrocurcumin, induced HO-1 expression and Nrf2 nuclear translocation, suggesting that the unsaturated nature of the diarylheptanoid chain of the compounds are crucial for HO-1 expression and Nrf2 activation. Blockage of Nrf2 synthesis by small interfering RNA abolished HO-1 expression by dimethoxycurcumin, indicating that dimethoxycurcumin may induce HO-1 expression via Nrf2 activation. In comparison, dimethoxycurcumin and curcumin had about the same effect on HO-1 expression, suggesting that dimethoxycurcumin retains the HO-1-inducing activity of its parent compound curcumin in RAW264.7 macrophages.
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