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Glabridin, an isoflavan from licorice root, downregulates iNOS expression and activity under high‐glucose stress and inflammation
Author(s) -
Yehuda Itamar,
Madar Zecharia,
LeikinFrenkel Alicia,
Tamir Snait
Publication year - 2015
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201400876
Subject(s) - nitrotyrosine , oxidative stress , endocrinology , medicine , inflammation , nitric oxide , chemistry , nitric oxide synthase , offspring , downregulation and upregulation , diabetes mellitus , biochemistry , biology , pregnancy , gene , genetics
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.