Abstract
The mechanism of inhibition of advanced glycation end product (AGE) formation by protocatechuic acid and 3,4-dihydroxyphenylacetic acid (DHPA) has been studied using a widespread applied in vitro model system composed of bovine serum albumin (BSA) and supraphysiological glucose concentrations. Protocatechuic acid and DHPA inhibited the formation of Amadori compounds, fluorescent AGEs (IC50 = 62.1 ± 1.4 and 155.4 ± 1.1 μmol/L, respectively), and Nε-(carboxymethyl)lysine (IC50 = 535.3 ± 1.1 and 751.2 ± 1.0 μmol/L, respectively). BSA was pretreated with the two phenolic acids, and the formation of BSA-phenolic acid adducts was estimated by nanoflow liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry. Results showed that the tested phenolic acids bound key sites of glycation in BSA through a metal-catalyzed oxidative mechanism. The antiglycative activity mechanism involved the formation of BSA-phenolic acid adducts, and it is unlikely that this occurs in vivo. These results raise the problem to design in vitro models closer to physiological conditions to reach biologically sound conclusions.
Highlights
Glycation of circulating, cellular, and matrix proteins by glucose are thought to be a major factor in pathogenesis of diabetes and related cardiovascular diseases.[1]
The ability of protocatechuic acid and DHPA to inhibit protein glycation was assayed by measuring the formation of fluorescent advanced glycation end products (AGEs)
The data obtained by ELISA assay demonstrated that protocatechuic acid was more effective in the inhibition of CML formation than DHPA
Summary
Cellular, and matrix proteins by glucose are thought to be a major factor in pathogenesis of diabetes and related cardiovascular diseases.[1] This process is known as the Maillard reaction and begins with the nucleophilic addition between an amino group of a protein and the carbonyl group of glucose to form a reversible Schiff base (Figure 1 pathway 1).[2] The latter can rearrange in Amadori compounds, that can be fragmented by oxidation in presence of reactive oxygen species (ROS) and transition metal ions such as Fe3+ and Cu2+ (Figure 1 pathway 2) This oxidative degradation could lead to the formation of the so called advanced glycation end products (AGEs). Glucose can be directly oxidized in the presence of catalytic metals and ROS, generating dicarbonyl compounds (Figure 1 pathway 3) which can further react with the amino groups of proteins (Figure 1 pathway 5).[3,4]
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