Glabridin, a phytoestrogen from licorice root, up-regulates manganese superoxide dismutase, catalase and paraoxonase 2 under glucose stress.
The risk of death from cardiovascular diseases (CVDs), which are exacerbated by oxidative stress, is higher in diabetic women. This phenomenon has been attributed to the loss of estradiol-vascular protection. Such knowledge led us to examine the potential of glabridin, a phytoestrogen, to substitute estradiol up-regulation of antioxidant enzymes under high glucose conditions. Chronic glucose stress was found to down-regulate catalase (CAT) and paraoxonase 2 (PON2) mRNA expression by 20% and 17%, respectively, and to decrease PON2 activity by 83% in macrophages. Inflammatory conditions had an additive effect on PON2 expression in a time-dependent manner. Treatment with glabridin, under high glucose stress, increased PON2 activity by 60% and up-regulated its mRNA expression by 3.5 fold. Furthermore, glabridin up-regulated the expression of manganese superoxide dismutase (Mn-SOD) and CAT in monocytes. In conclusion, glabridin has the potential of strengthening the antioxidant defense mechanism and may serve as an antiatherogenic agent in diabetes.
Laboratory of Human Health and Nutrition Sciences, MIGAL-Galilee Technology Center, Kiryat-Shmona, Israel.
Itamar
I
Yehuda
Zecharia
Z
Madar
Andrea
A
Szuchman-Sapir
Snait
S
Tamir
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D043303:Aryldialkylphosphatase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D002374:Catalase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006035:Glycyrrhiza / Q000737:chemistry*; D006801:Humans; D007529:Isoflavones / Q000737:chemistry / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology; D018384:Oxidative Stress; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D048789:Phytoestrogens / Q000378:metabolism / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D013312:Stress, Physiological; D013482:Superoxide Dismutase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000975:Antioxidants; D007529:Isoflavones; D010636:Phenols; D048789:Phytoestrogens; D017382:Reactive Oxygen Species; D004958:Estradiol; D002374:Catalase; D013482:Superoxide Dismutase; D043303:Aryldialkylphosphatase; C107601:glabridin; D005947:Glucose