Itamar Yehuda1,2, Zecharia Madar2, Alicia Leikin-Frenkel3,4, Snait Tamir1,5. 1. Laboratory of Human Health and Nutrition Sciences, MIGAL-Galilee Research Institute, Kiryat-Shmona, Israel. 2. The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Jerusalem, Israel. 3. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. 4. Sheba Medical Center, Bert W. Strassburger Lipid Center, Tel-Hashomer, Israel. 5. Faculty of Sciences and Technology, Tel-Hai Academic College, Upper Galilee, Israel.
Abstract
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.
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.
Authors: Sara Franceschelli; Daniela Maria Pia Gatta; Mirko Pesce; Alessio Ferrone; Antonia Patruno; Maria Anna de Lutiis; Alfredo Grilli; Mario Felaco; Fausto Croce; Lorenza Speranza Journal: Int J Mol Sci Date: 2016-09-01 Impact factor: 5.923
Authors: Mohammad Hosein Farzaei; Amit Kumar Singh; Ramesh Kumar; Courtney R Croley; Abhay K Pandey; Ericsson Coy-Barrera; Jayanta Kumar Patra; Gitishree Das; Rout George Kerry; Giuseppe Annunziata; Gian Carlo Tenore; Haroon Khan; Matteo Micucci; Roberta Budriesi; Saeideh Momtaz; Seyed Mohammad Nabavi; Anupam Bishayee Journal: Int J Mol Sci Date: 2019-10-08 Impact factor: 5.923