Iron complexing activity of mangiferin, a naturally occurring glucosylxanthone, inhibits mitochondrial lipid peroxidation induced by Fe2+-citrate

Eur J Pharmacol. 2005 Apr 18;513(1-2):47-55. doi: 10.1016/j.ejphar.2005.03.007. Epub 2005 Apr 1.


Mangiferin, a naturally occurring glucosylxanthone, has been described as having antidiabetic, antiproliferative, immunomodulatory and antioxidant activities. In this study we report for the first time the iron-complexing ability of mangiferin as a primary mechanism for protection of rat liver mitochondria against Fe(2+)-citrate induced lipid peroxidation. Thiobarbituric acid reactive substances and antimycin A-insensitive oxygen consumption were used as quantitative measures of lipid peroxidation. Mangiferin at 10 microM induced near-full protection against 50 microM Fe(2+)-citrate-induced mitochondrial swelling and loss of mitochondrial transmembrane potential (DeltaPsi). The IC(50) value for mangiferin protection against Fe(2+)-citrate-induced mitochondrial thiobarbituric acid reactive substance formation (9.02+/-1.12 microM) was around 10 times lower than that for tert-butylhydroperoxide mitochondrial induction of thiobarbituric acid reactive substance formation. The xanthone derivative also inhibited the iron citrate induction of mitochondrial antimycin A-insensitive oxygen consumption, stimulated oxygen consumption due to Fe(2+) autoxidation and prevented Fe(3+) ascorbate reduction. Absorption spectra of mangiferin-Fe(2+)/Fe(3+) complexes also suggest the formation of a transient charge transfer complex between Fe(2+) and mangiferin, accelerating Fe(2+) oxidation and the formation of a more stable Fe(3+)-mangiferin complex unable to participate in Fenton-type reaction and lipid peroxidation propagation phase. In conclusion, these results show that in vitro antioxidant activity of mangiferin is related to its iron-chelating properties and not merely due to the scavenging activity of free radicals. These results are of pharmacological relevance since mangiferin and its naturally contained extracts could be potential candidates for chelation therapy in diseases related to abnormal intracellular iron distribution or iron overload.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ascorbic Acid / pharmacology
  • Citrates / pharmacology
  • Dose-Response Relationship, Drug
  • Ferric Compounds / chemistry
  • Ferric Compounds / metabolism
  • Ferric Compounds / pharmacology
  • Ferrous Compounds / chemistry
  • Ferrous Compounds / metabolism
  • Iron Chelating Agents / pharmacology*
  • Lipid Peroxidation / drug effects*
  • Membrane Potentials / drug effects
  • Mitochondria, Liver / drug effects*
  • Mitochondria, Liver / metabolism
  • Mitochondrial Swelling / drug effects
  • Mitochondrial Swelling / physiology
  • Oxidation-Reduction / drug effects
  • Oxygen Consumption / drug effects
  • Rats
  • Sodium Citrate
  • Spectrophotometry
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Xanthones / chemistry
  • Xanthones / pharmacology*


  • Citrates
  • Ferric Compounds
  • Ferrous Compounds
  • Iron Chelating Agents
  • Thiobarbituric Acid Reactive Substances
  • Xanthones
  • mangiferin
  • Sodium Citrate
  • Ascorbic Acid