Oxidative Transformation of Demethoxy- and Bisdemethoxycurcumin: Products, Mechanism of Formation, and Poisoning of Human Topoisomerase IIα.
Oxidative Transformation of Demethoxy- and Bisdemethoxycurcumin: Products, Mechanism of Formation, and Poisoning of Human Topoisomerase IIα.
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DOI：
10.1021/acs.chemrestox.5b00009
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发表时间：
2015-05-18
影响因子：
4.1
通讯作者：
Schneider, Claus
中科院分区：
文献类型：
--
作者：
Gordon, Odaine N.;Luis, Paula B.;Ashley, Rachel E.;Osheroff, Neil;Schneider, Claus
从姜黄植物根茎中提取的提取物被广泛用作抗炎膳食补充剂。姜黄提取物含有三种姜黄素，姜黄素(≈80%相对丰度)、去甲氧基姜黄素(≈15%)和双去甲氧基姜黄素(BDMC；≈5%)。纯姜黄素的一个明显特征是在生理pH下不稳定，导致在10-15分钟内迅速自氧化为双环戊二酮。在这里，我们描述了姜黄提取物、DMC和BDMC的氧化转化，并用LC-MS和核磁共振分析鉴定了它们的氧化产物。DMC在24小时内自动氧化成预期的双环戊二酮非对映异构体。BDMC耐自氧化，氧化转化需要辣根过氧化物酶和H_2O_2或铁氰化钾催化。BDMC的氧化产物是一种稳定的螺环氧化物，相当于姜黄素自氧化的反应中间体。在铁氰化钾的存在下，脱氧核糖核酸和脱氧核糖核酸对重组人拓扑异构酶IIα的毒性作用显着增强，表明需要氧化转化才能获得完整的DNA切割活性。DMC和BDMC比姜黄素更不容易自氧化，有助于提高姜黄提取物在生理pH下的稳定性。它们的氧化代谢产物可能与姜黄提取物的生物学效应有关。
Extracts from the rhizome of the turmeric plant are widely consumed as anti-inflammatory dietary supplements. Turmeric extract contains the three curcuminoids, curcumin (≈80% relative abundance), demethoxycurcumin (DMC; ≈15%), and bisdemethoxycurcumin (BDMC; ≈5%). A distinct feature of pure curcumin is its instability at physiological pH resulting in rapid autoxidation to a bicyclopentadione within 10–15 min. Here, we describe oxidative transformation of turmeric extract, DMC, and BDMC, and the identification of their oxidation products using LC-MS and NMR analyses. DMC autoxidized over the course of 24 h to the expected bicyclopentadione diastereomers. BDMC was resistant to autoxidation, and oxidative transformation required catalysis by horseradish peroxidase and H2O2 or potassium ferricyanide. The product of BDMC oxidation was a stable spiroepoxide that was equivalent to a reaction intermediate in the autoxidation of curcumin. The ability of DMC and BDMC to poison recombinant human topoisomerase IIα was significantly increased in the presence of potassium ferricyanide indicating that oxidative transformation was required to achieve full DNA cleavage activity. DMC and BDMC are less prone to autoxidation than curcumin and contribute to the enhanced stability of turmeric extract at physiological pH. Their oxidative metabolites may contribute to the biological effects of turmeric extract.
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DOI：
10.1038/nrc2607
发表时间：
2009-05
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1038/nrc2608
发表时间：
2009-05
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.1
作者：
Lopez-Lazaro, Miguel;Willmore, Elaine;Austin, Caroline A.
通讯作者：
Austin, Caroline A.
影响因子：
1.8
作者：
Gordon, Odaine N.;Graham, Leigh A.;Schneider, Claus
通讯作者：
Schneider, Claus
DOI：
10.1080/14756360310001613085
发表时间：
2003-12-01
影响因子：
5.6
作者：
Martín-Cordero, C;López-Lázaro, M;Ayuso, MJ
通讯作者：
Ayuso, MJ