Glabridin, an isoflavan from licorice root, downregulates iNOS expression and activity under high-glucose stress and inflammation

Scope: In females, hyperglycemia abolishes estrogen-vascular protection, leading to inflammation and oxidative stress that are related to diabetes-associated cardiovascular complications. Such knowledge led us to examine the potential of glabridin, as a replacement of estrogen anti-inflammatory activity under high-glucose conditions. Methods and results: In macrophage-like cells, chronic glucose stress (28 and 44 mM) upregulated inducible nitric oxide synthase (iNOS) mRNA expression by 42 and 189%, respectively. Pretreatment with glabridin, under chronic glucose stress, downregulated the LPS-induced nitric oxide secretion and nitrotyrosine formation, by 39 and 21%, respectively. Pretreatment with estradiol did not prevent the LPS-induced nitrotyrosine formation. Furthermore, glabridin, brought about a decrease in the LPS-induced iNOS mRNA expression by 48%, as compared to cells pretreated with estradiol. Glabridin decreased protein levels of liver iNOS by 69% in adult mouse offspring which developed hyperglycemia after early fetal exposure to a saturated fatty acid-enriched maternal diet. Glabridin also decreased liver nitrotyrosine levels in offspring of regular diet-fed mothers after further receiving high-fat diet. Conclusion: Such results indicate that glabridin retains anti-inflammatory abilities to regulate the synthesis and activity of iNOS under high-glucose levels, implying that a glabridin supplement may serve as an anti-inflammatory agent in diabetes-related vascular dysfunction.