The inhibitory effects of natural antioxidants on protein glycation as well as aggregation induced by methylglyoxal and underlying mechanisms

Abstract

The non-enzymatic glycation of protein can result in the formation of advanced glycation end-products (AGEs), leading to the deposition of amyloid proteins, and it’s essential for the pathogenesis of diabetes complications and amyloid diseases. Reactive dicarbonyl compounds, such as methylglyoxal (MGO), are one of the most reactive glycating agents. Therefore, it’s crucially necessary to inhibit protein glycation and aggregation induced by MGO. In the present study, we aimed to systemically investigate the anti-glycation and anti-fibrillization activities of eight natural antioxidants, including apigenin, quercetin (Que), catechin, resveratrol (Res), and gallic acid (GA), L-ascorbic acid (L-AA), limonene, and β-carotene, during MGO-induced protein glycation and aggregation. Furthermore, the underlying mechanisms were clarified. The formation of AGEs and the degree of protein aggregation were characterized by optical detection, flow cytometry, and so on. The results demonstrated that eight selected natural antioxidants could inhibit glycation and protein aggregation induced by MGO via the synergy of scavenging free radicals, capturing MGO, and interacting with proteins, among which GA (300 μM) and Res (15 μM) had higher inhibition rates on both argpyrimidine (specific fluorescent AGEs, 17% and 22%, respectively) and protein amyloid aggregation (42% and 29%, respectively). These findings suggested that antioxidants could act as potential inhibitors of AGEs and glycation-induced protein aggregation, which were expected to become a new strategy for the prevention and treatment of diabetes and amyloid diseases. Besides, these inhibition mechanisms provided valuable insights into the design and development of candidate drugs for the prevention and treatment of AGEs and protein aggregation-related diseases.