Glabridin, an isoflavan from licorice root, upregulates paraoxonase 2 expression under hyperglycemia and protects it from oxidation

Itamar Yehuda, Zecharia Madar, Alicia Leikin-Frenkel, Andrea Szuchman-Sapir, Faiga Magzal, Gilad Markman, Snait Tamir*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Scope: Hyperglycemia is associated with oxidative stress, which accelerates cardiovascular complications. This study investigates the potential of glabridin to regulate paraoxonase 2 (PON2) levels, in vivo, and explores the glabridin protective effect on PON2 through tryptophan-fluorescence quenching and mass spectrometry. Methods and results: Adult mouse offspring of saturated fatty acids fed mothers, which developed hyperglycemia after exposure to a high fat diet in their adult life, had lower levels of heart PON2 mRNA and protein expression than did the control mice (64 and 26%, respectively). Glabridin supplementation significantly upregulated PON2 mRNA and protein expression in the liver (2.1-fold and 2.6-fold, respectively) and heart (2.5-fold and 1.6-fold, respectively) in these mice. In vitro studies demonstrated that the fluorescence quenching of PON2 by glabridin was a result of the formation of a glabridin-PON2 interaction. The binding constant (7.61 × 105 M-1) and the ΔG (-33.55kJ/mol) indicated that this interaction was driven by a hydrophobic force, which confers protection against CuSO4-induced PON2 oxidation. Conclusion: Such results indicate that glabridin preserves the anti-atherogenic abilities of PON2 by maintaining its levels, in vivo. The glabridin-PON2 interaction may be the mechanism by which glabridin protects PON2 from oxidation, thus contributing to the protection of PON2 activity in hyperglycemia.

Original languageEnglish
Pages (from-to)287-299
Number of pages13
JournalMolecular Nutrition and Food Research
Volume60
Issue number2
DOIs
StatePublished - 1 Feb 2016

Bibliographical note

Publisher Copyright:
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Keywords

  • Diabetes
  • Glabridin
  • Mass spectroscopy
  • Oxidative stress
  • Paraoxonase 2
  • Tryptophan-fluorescence quenching

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