Protein glycation in human bodies can lead to the malfunction of intracellular and extracellular proteins. Products from such a reaction, generally termed as advanced glycation end products (AGEs), play important roles in the pathogenesis of nephropathy, neuropathy and retinopathy in diabetic patients. Therefore, the inhibition of AGEs formation has been recognized as one of the most promising strategies for the prevention of these devastating complications. An effective therapeutic approach is by scavenging the reactive carbonyl intermediates (particularly dicarbonyls) of AGEs. Several synthetic reactive carbonyl scavengers have already entered clinical trials with some successes, indicating a sound scientific basis for the application of reactive carbonyl scavengers in the treatment and prevention of diabetic complications. While there are reservations about the side effects of synthetic drugs, the concept of reactive carbonyl-scavenging has been under-explored in natural product research in relation to amelioration of diabetic complications. In this study, we aim to evaluate the bioactivity and action mechanism of phenolic-type reactive carbonyl scavengers by chemical and molecular biological approaches. Three natural phenolics, apigenin, cyanomaclurin and phloretin which possess similar antioxidant activity and different strength of carbonyl scavenging capacity are selected. Their effects on the formation of AGEs, oxidative stress, and AGEs-induced apoptosis and inflammation, some phenomena closely linked to diabetic nephropathy, will be tested in human umbilical vein endothelial cells. Instrumental analysis, Western blotting, immunocytochemistry and real-time RT-PCR will be applied to mechanistically evaluate their carbonyl scavenging potentiality in cells and whether their carbonyl scavenging capacity or antioxidant activity is responsible for their health benefits; and to further reveal some molecular mechanisms related to their potential activity against AGEs-induced cell apoptosis and inflammation (Bcl-2, Bax/Bad, MCP-1, IL-6, ICAM-1, TGF-β1, and RAGE expression).<br/>

Phenolic-type reactive carbonyl scavengers as inhibitors against the formation of advanced glycation end products (AGEs) and AGEs-induced endothelial cell apoptosis and inflammation

254th National Meeting (2017)

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