Gordon Odaine N, Luis Paula B, Ashley Rachel E, Osheroff Neil, Schneider Claus
Departments of †Pharmacology (Clinical Pharmacology), ‡Biochemistry, and §Medicine (Hematology/Oncology), ||Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical School, Nashville, Tennessee 37232, United States.
Chem Res Toxicol. 2015 May 18;28(5):989-96. doi: 10.1021/acs.chemrestox.5b00009. Epub 2015 Apr 3.
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.
姜黄植物根茎提取物作为抗炎膳食补充剂被广泛食用。姜黄提取物含有三种姜黄素类化合物，即姜黄素（相对丰度约为80%）、去甲氧基姜黄素（DMC；约15%）和双去甲氧基姜黄素（BDMC；约5%）。纯姜黄素的一个显著特点是其在生理pH值下不稳定，会在10 - 15分钟内迅速自氧化为双环戊二酮。在此，我们描述了姜黄提取物、DMC和BDMC的氧化转化过程，并通过液相色谱 - 质谱联用（LC - MS）和核磁共振（NMR）分析鉴定了它们的氧化产物。DMC在24小时内自氧化为预期的双环戊二酮非对映异构体。BDMC对自氧化具有抗性，其氧化转化需要辣根过氧化物酶和过氧化氢或铁氰化钾催化。BDMC氧化产物是一种稳定的螺环氧，等同于姜黄素自氧化过程中的反应中间体。在铁氰化钾存在下，DMC和BDMC使重组人拓扑异构酶IIα失活的能力显著增强，表明需要氧化转化才能实现完全的DNA切割活性。与姜黄素相比，DMC和BDMC较不易自氧化，这有助于提高姜黄提取物在生理pH值下的稳定性。它们的氧化代谢产物可能对姜黄提取物的生物学效应有贡献。
