Abstract:
Protein glycation is a non-enzymatic modification of protein by reducing sugars (such as glucose and fructose) or dicarbonyl molecules (such as methylglyoxal), resulting in the formation of advanced glycation end products (AGEs) which have been considered to be a significant contributor of age-related diseases and diabetic complications. Isoferulic acid (IFA), one of cinnamic acid derivatives in plants and rhizome of Cimicifuga species, has been shown various pharmacological activities including anti-oxidation and anti-hyperglycemia. The objectives of the present study were to investigate anti-glycation property of IFA in different models including bovine serum albumin (BSA), deoxyribonucleic acid (DNA) and pancreatic β cell. The results showed that IFA (1.25-5 mM) inhibited formation of fluorescent and non-fluorescent AGE, Amadori product (fructosamine), protein carbonyl content, loss of protein thiol groups, and amyloid cross β structure in BSA glycation induced by glucose, fructose and methylglyoxal. IFA (0.1-1 mM) prevented oxidative DNA strand breakage and suppressed superoxide anion and hydroxyl radical production induced by MG and lysine, however, the result from HPLC indicated that IFA did not directly trap MG. In pancreatic β cell, IFA (0.1 mM) prevented β-cell dysfunction by reducing intracellular reactive oxygen species (ROS) and uncoupling protein 2 (UCP2) expression, and improving insulin secretion. Although IFA could not elevate ATP level, it increased glyoxalase I activity in MG-detoxification system and β-cell viability, and also inhibited caspase-3 activity in β cell induced by MG. From these findings, IFA might be considered or applied to use in prevention of AGE-mediated diabetic complications.
