Advanced Glycation End Product Inhibitory Effect of Quercetin-3-O- Rutinoside, Isolated from Teucrium polium

Introduction Reactive oxygen species (ROS) have been shown to play a critical role in many diseases such as diabetes mellitus, cancer, Alzheimer, arteriosclerosis and other conditions. Chronic glucose levels in blood or cells of diabetic patients are known to cause oxidative damages, followed by an increasing in ROS production and/or dysfunction of antioxidant defense system (enzyme or non-enzymatic) in biological systems. Several mechanism including autoxidation of glucose, protein glycation and advanced glycation end products (AGEs) formation may to be involved in hyperglycemia mediated oxidative stress. Non enzymatic protein glycation initiated by the reversible formation of a Schiff base which leads to formation of heterogeneous and toxic advanced glycation end products (AGEs). The accumulation of the reaction products of protein glycation in living organisms leads to structural and functional modifications of tissue proteins. Regarding the significance of oxidative stress to diabetic pathology, numerous natural and synthetic ROS scavengers and antioxidants have been evaluated to inhibit the process of protein modifications against the attack of ROS and/or to suppress the resultant damages. In spite of the sufficient effects of aminoguanidine (AG) on diabetic complications, its consumption has been associated with some deleterious side effects such as drug resistance and hepatotoxicity. Thus, consumption of complementary components (mainly from plant sources), with an antioxidant effect and low side effects, make them good candidates for the development of new functional drugs with potential protective and/or prevention properties against oxidative stress-related diseases such as diabetes and its complications. In an attempt to find new antioxidants agents from plant materials as therapeutic agents, we are interested in the development of antioxidants that have potent anti-glycation activity. Teucrium polium was used as a hypoglycemic agent in folk medicine in Iran. The biological activities of T. polium including antiinflammatory, anti-nociceptive, anti-bacterial, antihypertensive, hypolipidemic, anti-rheumatoid, and hypoglycemic widely has been reportd. 8-10 Recently, Esmaeili and Yazdanparast, showed the high insulinotropic and anti-hyperglycemic activity of T. polium crude extract using both animal and/or isolated rat pancreatic islets. There are also some data in literature about antioxidant activity of various crude extract of T. polium. 12, 13 Based on these data, the present study was hence, undertaken to isolate and Background: Several mechanism including autoxidation of glucose, protein glycation and advanced glycation end products (AGEs) formation may to be involved in hyperglycemia mediated oxidative stress. Herein, in this study, the effects of rutin with high antioxidant activity isolated from Teucrium polium on structural changes of human serum albumin (HSA) were performed. Methods: The major compounds of T. polium methanol extract were isolated and their radical scavenging properties were established through various approaches including 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl radicals scavenging, and reducing power. The structural changes of HSA with glucose, in the presence of rutin were studied with far-UV CD spectroscopy. Results: Based on our results, rutin, a flavonol glycoside isolated from T. polium exhibited high antioxidant activity compared to the other isolated compounds from T. polium. Rutin inhibited high glucose induced oxidative damages to protein by decreasing protein carbonyl formation (PCO) and preventing thiols group from oxidation. In addition, evaluating the structural changes of HSA by glucose in the presence of rutin showed that rutin may be able to increase the helicity of the protein and prevent helix decrement in the secondary structure of HSA. Conclusion: We found that rutin with high antioxidant activity effectively inhibited the generation of amadori products and exhibited good inhibitory effects on the formations of αdicarbonyl compounds and AGEs. A R T I C L E I N F O A B S T R A C T