Abstract
Iron overload disorders may be treated by chelation therapy. This study describes a novel method for isolating iron chelators from complex mixtures including plant extracts. We demonstrate the one-step isolation of curcuminoids from turmeric, the medicinal food spice derived from Curcuma longa. The method uses iron-nitrilotriacetic acid (NTA)-agarose, to which curcumin binds rapidly, specifically, and reversibly. Curcumin, demethoxycurcumin, and bisdemethoxycurcumin each bound iron-NTA-agarose with comparable affinities and a stoichiometry near 1. Analyses of binding efficiencies and purity demonstrated that curcuminoids comprise the primary iron binding compounds recovered from a crude turmeric extract. Competition of curcuminoid binding to the iron resin was used to characterize the metal binding site on curcumin and to detect iron binding by added chelators. Curcumin-Iron-NTA-agarose binding was inhibited by other metals with relative potency: (>90% inhibition) Cu2+ ~ Al3+ > Zn2+ ≥ Ca2+ ~ Mg2+ ~ Mn2+ (<20% inhibition). Binding was also inhibited by pharmaceutical iron chelators (desferoxamine or EDTA) or by higher concentrations of weak iron chelators (citrate or silibinin). Investigation of the physiological effects of iron binding by curcumin revealed that curcumin uptake by cultured cells was reduced >80% by addition of iron to the media; uptake was completely restored by desferoxamine. Ranking of metals by relative potencies for blocking curcumin uptake agreed with their relative potencies in blocking curcumin binding to iron-NTA-agarose. We conclude that curcumin can selectively bind toxic metals including iron in a physiological setting, and propose inhibition of curcumin binding to iron-NTA-agarose for iron chelator screening.
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Acknowledgements
We gratefully acknowledge Cheryl Wong and Brian S. Kunakom, Bastyr University, for technical assistance and supporting experiments. We thank Dr. Muhammed Majeed and colleagues at Sabinsa Corporation for generously providing the purified curcuminoids (C3 complex®) and turmeric used in this study. Preliminary aspects of this work appeared in abstract form (Messner et al. FASEB J April 2015 29:773.7). Supported by the National Center for Complementary and Alternative Medicine (Grant AT3448 to DJM).
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Messner, D.J., Surrago, C., Fiordalisi, C. et al. Isolation and characterization of iron chelators from turmeric (Curcuma longa): selective metal binding by curcuminoids. Biometals 30, 699–708 (2017). https://doi.org/10.1007/s10534-017-0038-6
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DOI: https://doi.org/10.1007/s10534-017-0038-6