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


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.


CONCLUSIONS
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.
Laboratory of Human Health and Nutrition Sciences, MIGAL-Galilee Research Institute, Kiryat-Shmona, Israel.|The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Jerusalem, Israel.
Itamar
I
Yehuda
The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Jerusalem, Israel.
Zecharia
Z
Madar
Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.|Sheba Medical Center, Bert W. Strassburger Lipid Center, Tel-Hashomer, Israel.
Alicia
A
Leikin-Frenkel
Laboratory of Human Health and Nutrition Sciences, MIGAL-Galilee Research Institute, Kiryat-Shmona, Israel.|Faculty of Sciences and Technology, Tel-Hai Academic College, Upper Galilee, Israel.
Snait
S
Tamir
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D006035:Glycyrrhiza / Q000737:chemistry*; D006943:Hyperglycemia / Q000188:drug therapy; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D007529:Isoflavones / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000009:adverse effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism; D015854:Up-Regulation
D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; D007529:Isoflavones; D008070:Lipopolysaccharides; D010636:Phenols; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C107601:glabridin
Chronic glucose stress; Glabridin; Inducible nitric oxide synthase; Inflammation; Oxidative stress