Oxidative Transformation of Demethoxy- and Bisdemethoxycurcumin: Products, Mechanism of Formation, and Poisoning of Human Topoisomerase IIα
Year: 2015
Type: article
Abstract: 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.
Source: Chemical Research in Toxicology
Institution: Vanderbilt University
Language: English
Subfield: Molecular Medicine
Domain: Life Sciences
Open Access status: green
Funders: National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Complementary and Alternative Medicine, Division of Graduate Education, National Center for Complementary and Integrative Health
Awards: G137996285, G1806196891, Pharmacokinetics and Metabolism of Oxidized Curcumin, Training in Pharmacological Sciences, Oxidative activation of the dietary cancer chemopreventive agent curcumin, G4041358501, G4143725281, SPORE in GI Cancer, Initiative for Maximizing Student Development, G5380432289, Function and Biology of Eukaryotic DNA Topoisomerases, G6702416931, Oxidative Metabolites of Curcumin and their Biological Activity, G8826926869, Molecular and Cellular Basis for Digestive Diseases
OpenAlex ID: W2013744555