title: Ellagic acid, a new antiglycating agent: its inhibition of Nϵ-(carboxymethyl)lysine.
abstract: Non-enzymatic glycation is a complex series of reactions between reducing sugars and amino groups of proteins. Accumulation of AGEs (advanced glycation end-products) due to non-enzymatic glycation has been related to several diseases associated with aging and diabetes. The formation of AGEs is accelerated in hyperglycaemic conditions, which alters the structure and function of long-lived proteins, thereby contributing to long-term diabetic complications. The present study describes AGE inhibition and the mechanism of action of a new antiglycating agent, EA (ellagic acid), a flavonoid present in many dietary sources. Inhibition of AGE formation by EA was demonstrated with different proteins, namely eye lens TSP (total soluble protein), Hb (haemoglobin), lysozyme and BSA, using different glycating agents such as fructose, ribose and methylglyoxal by a set of complementary methods. These results suggest that the antiglycating action of EA seems to involve, apart from inhibition of a few fluorescent AGEs, predominantly inhibition of CEL [Nϵ-(carboxyethyl)lysine] through scavenging of the dicarbonyl compounds. Furthermore, MALDI-TOF-MS (matrix-assisted laser-desorption ionisation-time-of-flight MS) analysis confirms inhibition of the formation of CEL on lysozyme on in vitro glycation by EA. Prevention of glycation-mediated β-sheet formation in Hb and lysozyme by EA confirm its antiglycating ability. Inhibition of glycosylated Hb formation in human blood under ex vivo high-glucose conditions signifies the physiological antiglycating potential of EA. We have also determined the effectiveness of EA against loss of eye lens transparency through inhibition of AGEs in the lens organ culture system. These findings establish the antiglycating potential of EA and its in vivo utility in controlling AGE-mediated diabetic pathologies.
authors: Biochemistry Division, National Institute of Nutrition, Tarnaka, Hyderabad 500 604, India.
authors: Puppala
authors: P
authors: Muthenna
authors: Chandrasekhar
authors: C
authors: Akileshwari
authors: G Bhanuprakash
authors: GB
authors: Reddy
mesh_terms: D000818:Animals; D003459:Crystallins / Q000737:chemistry / Q000187:drug effects; D048909:Diabetes Complications / Q000517:prevention & control; D004610:Ellagic Acid / Q000494:pharmacology*; D005942:Gluconates / Q000737:chemistry; D006442:Glycated Hemoglobin / Q000096:biosynthesis; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000276:immunology; D006801:Humans; D007783:Lactones / Q000737:chemistry; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D008297:Male; D009113:Muramidase / Q000737:chemistry / Q000187:drug effects; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D003459:Crystallins; D004610:Ellagic Acid; D005942:Gluconates; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D007783:Lactones; D008239:Lysine; D009113:Muramidase; C054688:N(6)-(1-carboxyethyl)lysine; C048496:N(6)-carboxymethyllysine; C010730:beta-glucono-1,5-lactone