TY - JOUR
T1 - Glabridin, an isoflavan from licorice root, upregulates paraoxonase 2 expression under hyperglycemia and protects it from oxidation
AU - Yehuda, Itamar
AU - Madar, Zecharia
AU - Leikin-Frenkel, Alicia
AU - Szuchman-Sapir, Andrea
AU - Magzal, Faiga
AU - Markman, Gilad
AU - Tamir, Snait
N1 - Publisher Copyright:
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - 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.
AB - 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.
KW - Diabetes
KW - Glabridin
KW - Mass spectroscopy
KW - Oxidative stress
KW - Paraoxonase 2
KW - Tryptophan-fluorescence quenching
UR - http://www.scopus.com/inward/record.url?scp=84949184519&partnerID=8YFLogxK
U2 - 10.1002/mnfr.201500441
DO - 10.1002/mnfr.201500441
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C2 - 26455358
AN - SCOPUS:84949184519
SN - 1613-4125
VL - 60
SP - 287
EP - 299
JO - Molecular Nutrition and Food Research
JF - Molecular Nutrition and Food Research
IS - 2
ER -