Isolation and characterization of iron chelators from turmeric (Curcuma longa): selective metal binding by curcuminoids

Biometals. 2017 Oct;30(5):699-708. doi: 10.1007/s10534-017-0038-6. Epub 2017 Aug 11.

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.

Keywords: Curcuma longa; Curcumin; Iron; Metal chelation; Turmeric.

MeSH terms

  • Aluminum / metabolism
  • Aluminum / pharmacology
  • Animals
  • Binding, Competitive
  • Calcium / metabolism
  • Calcium / pharmacology
  • Cell Line
  • Chromatography, Affinity / methods
  • Copper / metabolism
  • Copper / pharmacology
  • Curcuma / chemistry*
  • Curcumin / analogs & derivatives*
  • Curcumin / isolation & purification*
  • Curcumin / metabolism
  • Curcumin / pharmacology
  • Deferoxamine / metabolism
  • Deferoxamine / pharmacology
  • Diarylheptanoids
  • Edetic Acid / metabolism
  • Edetic Acid / pharmacology
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Ferric Compounds / chemistry
  • Iron / metabolism*
  • Iron Chelating Agents / isolation & purification*
  • Iron Chelating Agents / metabolism
  • Iron Chelating Agents / pharmacology
  • Kinetics
  • Liver / cytology
  • Liver / drug effects
  • Liver / metabolism
  • Magnesium / metabolism
  • Magnesium / pharmacology
  • Manganese / metabolism
  • Manganese / pharmacology
  • Nitrilotriacetic Acid / analogs & derivatives
  • Nitrilotriacetic Acid / chemistry
  • Plant Extracts / chemistry
  • Rats
  • Zinc / metabolism
  • Zinc / pharmacology

Substances

  • Diarylheptanoids
  • Ferric Compounds
  • Iron Chelating Agents
  • Plant Extracts
  • bisdemethoxycurcumin
  • Manganese
  • Copper
  • turmeric extract
  • Edetic Acid
  • Aluminum
  • Iron
  • Magnesium
  • Curcumin
  • Deferoxamine
  • Zinc
  • Nitrilotriacetic Acid
  • Calcium
  • demethoxycurcumin
  • ferric nitrilotriacetate