title: Glabridin, an isoflavan from licorice root, upregulates paraoxonase 2 expression under hyperglycemia and protects it from oxidation.
abstract: METHODS
  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.
  
  
  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 × 10(5) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Human Health and Nutrition Sciences, MIGAL-Galilee Research Institute, Kiryat-Shmona, Israel.|The Hebrew University of Jerusalem, The Robert H. Smith Faculty of Agriculture, Food and Environment, Institute of Biochemistry, Food Science and Nutrition, Rehovot, Israel.
authors.forename: Itamar
authors.initials: I
authors.lastname: Yehuda
authors.affiliation: The Hebrew University of Jerusalem, The Robert H. Smith Faculty of Agriculture, Food and Environment, Institute of Biochemistry, Food Science and Nutrition, Rehovot, Israel.
authors.forename: Zecharia
authors.initials: Z
authors.lastname: Madar
authors.affiliation: Tel Aviv University, Sackler School of Medicine, Tel Aviv, Israel.|Sheba Medical Center, Bert W. Strassburger Lipid Center, Tel-Hashomer, Israel.
authors.forename: Alicia
authors.initials: A
authors.lastname: Leikin-Frenkel
authors.affiliation: Laboratory of Human Health and Nutrition Sciences, MIGAL-Galilee Research Institute, Kiryat-Shmona, Israel.|Tel-Hai College, Faculty of Sciences and Technology, Upper Galilee, Israel.
authors.forename: Andrea
authors.initials: A
authors.lastname: Szuchman-Sapir
authors.affiliation: Laboratory of Human Health and Nutrition Sciences, MIGAL-Galilee Research Institute, Kiryat-Shmona, Israel.|Eliachar Research Laboratory, Galilee Medical Center, Nahariya, Israel.|Faculty of Medicine in the Galilee, Bar Ilan University, Safed, Israel.
authors.forename: Faiga
authors.initials: F
authors.lastname: Magzal
authors.affiliation: Laboratory of Human Health and Nutrition Sciences, MIGAL-Galilee Research Institute, Kiryat-Shmona, Israel.
authors.forename: Gilad
authors.initials: G
authors.lastname: Markman
authors.affiliation: Laboratory of Human Health and Nutrition Sciences, MIGAL-Galilee Research Institute, Kiryat-Shmona, Israel.|Tel-Hai College, Faculty of Sciences and Technology, Upper Galilee, Israel.
authors.forename: Snait
authors.initials: S
authors.lastname: Tamir
mesh_terms: D000818:Animals; D043303:Aryldialkylphosphatase / Q000235:genetics* / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006035:Glycyrrhiza / Q000737:chemistry; D006943:Hyperglycemia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D007333:Insulin Resistance; D007529:Isoflavones / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D007529:Isoflavones; D010636:Phenols; D020011:Protective Agents; C578990:PON2 protein, mouse; D043303:Aryldialkylphosphatase; C107601:glabridin
keywords: Diabetes; Glabridin; Mass spectroscopy; Oxidative stress; Paraoxonase 2; Tryptophan-fluorescence quenching