Suppression of pro-inflammatory and proliferative pathways by diferuloylmethane (curcumin) and its analogues dibenzoylmethane, dibenzoylpropane, and dibenzylideneacetone: role of Michael acceptors and Michael donors.
Suppression of pro-inflammatory and proliferative pathways by diferuloylmethane (curcumin) and its analogues dibenzoylmethane, dibenzoylpropane, and dibenzylideneacetone: role of Michael acceptors and Michael donors.
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DOI：
10.1016/j.bcp.2011.09.001
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发表时间：
2011-12-15
影响因子：
5.8
通讯作者：
Aggarwal BB
中科院分区：
文献类型：
--
作者：
Anand P;Sung B;Kunnumakkara AB;Rajasekharan KN;Aggarwal BB
姜黄素是一种二阿魏酰甲烷，已被证明具有抗炎和抗增殖活性。姜黄素既有Michael受体单位又有Michael供体单位，其类似物二苯甲酰甲烷(DBM，甘草成分)和二苯甲酰丙烷(DBP)有Michael供体单位但没有Michael受体单位，类似物二亚苄基丙酮(DBA)有Michael受体单位。在目前的报告中，我们研究了DBM、DBP和DBA与姜黄素的关系，因为它们能够抑制肿瘤坏死因子诱导的NF-κB激活、NF-κB调节的基因产物和细胞增殖。结果表明，四种药物均具有抑制NF-κB活性的作用，其中姜黄素活性最强，去甲肾上腺素最弱。当检测其抑制核因子-κB的亚基p65的直接dna结合活性时，只有dBP抑制这种结合。在抑制肿瘤坏死因子诱导的IKK激活方面，DBA的活性最强。在抑制肿瘤坏死因子诱导的炎症标记物COX-2、增殖标记物细胞周期蛋白D_1、血管生成标记物血管内皮生长因子等基因产物的表达方面，去甲肾上腺素和姜黄素比去甲肾上腺素更有效。同样，在抑制白血病(KBM-5)、T细胞白血病(Jurkat)、前列腺癌(DU145)和乳腺癌细胞(MDA-MB-231)的增殖方面，姜黄素和DBA活性最强，DBP活性最低。总体而言，我们的结果表明，尽管姜黄素及其类似物具有抑制炎症途径和细胞增殖的活性，但DBM和DBP中缺乏Michael受体单位会降低它们的活性。
Curcumin, a diferuloylmethane, has been shown to exhibit anti-inflammatory and anti-proliferative activities. Whereas curcumin has both a Michael acceptor and a Michael donor units, its analogues dibenzoylmethane (DBM, a component of licorice) and dibenzoylpropane (DBP) have a Michael donor but not a Michael acceptor unit, and the analogue dibenzylideneacetone (DBA) has a Michael acceptor unit. In the current report, we investigated the potency of DBM, DBP, and DBA in relation to curcumin for their ability to suppress TNF-induced NF-κB activation, NF-κB-regulated gene products, and cell proliferation. We found that all four agents were active in suppressing NF-κB activation; curcumin was most active and DBM was least active. When examined for its ability to inhibit the direct DNA binding activity of p65, a subunit of NF-κB, only DBP inhibited the binding. For inhibition of TNF-induced IKK activation, DBA was most active. For suppression of TNF-induced expression of NF-κB regulated gene products such as COX-2 (inflammation marker), cyclin D1 (proliferation marker), and VEGF (angiogenesis marker), DBA and curcumin were more active than DBM. Similarly for suppression of proliferation of leukemia (KBM-5), T cell leukemia (Jurkat), prostate (DU145), and breast (MDA-MB-231) cancer cells, curcumin and DBA were most active and DBP was least active. Overall, our results indicate that although curcumin and its analogues exhibit activities to suppress inflammatory pathways and cellular proliferation, a lack of Michael acceptor units in DBM and DBP can reduce their activities.
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影响因子：
9.7
作者：
Jackson, KM;DeLeon, M;Harris, WB
通讯作者：
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影响因子：
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作者：
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DOI：
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