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.