Polyphenols with antiglycation activity and mechanisms of action: A review of recent findings

Abstract

Advanced glycation end products (AGEs) are substances composed of amino groups of proteins and reducing sugars. The initial and propagation phases of the glycation process are accompanied by the production of a large amount of free radicals, carbonyl species, and reactive dicarbonyl species, of which, methylglyoxal (MG) is the most reactive and can cause dicarbonyl stress, influencing normal physiological functions. In the advanced phase, the production of AGEs and the interaction between AGEs and their receptor, RAGE, are also considered to be among the causes of chronic diseases, oxidative stress, and inflammatory reaction. Till date, multiple physiological activities of polyphenols have been confirmed. Recently, there have been many studies discussing the ability of polyphenols to suppress the MG and AGEs formation, which was also confirmed in some in vivo studies. This review article collects recent literatures concerning the effects of polyphenols on the generation of MG and AGEs through different pathways and discusses the feasibility of the inhibition of glycative stress and dicarbonyl stress by polyphenols.

Keywords: advanced glycation end products; antiglycation; flavonoid; phenolic acid; polyphenols.

Figure 1

Pathway for AGE formation. The N-terminal amino groups of protein and reducing sugar form dicarbonyls including methylglyoxal, glyoxal, and 3-deoxyglucosone through polyol pathway, glycolysis, or autoxidation of reducing sugar, leading to generation of pathological AGEs. AGE=advanced glycation end product; CEL=N ^ɛ-carboxyethyllysine; CML=N ^ɛ-carboxymethyllysine; 3-dG=3-deoxyglucosone; DOLD=3-deoxyglucosone lysine dimer; GO=glyoxal; GOLD=glyoxal-lysine dimer; MG=methylglyoxal; MGH =MG-derived-hydroimidazalone; MOLD=methylglyoxal-lysine dimer.

Figure 2

Chemical structures of MG-derived AGEs. AGE=advanced glycation end product; CEL=N ^ɛ-carboxyethyllysine; MG=methylglyoxal; MG-H=MG-derived-hydroimidazalone; MODIC = imidazolium cross-link derived from methylglyoxal and lysine-arginine; MOLD=methylglyoxal-lysine dimer.

Figure 3

Glyoxalase system. The detoxification system of MG in all cells. GLO 1 plays a first step in catalyzing MG to s-D-Lactoylglutathione. It is a key enzyme in glyoxalase system for regulating the MG formation. MG=methylglyoxal; GLO = glyoxalase.

Figure 4

Antiglycation mechanisms of polyphenols. Several strategies are designed of AGE inhibitor. (1) Inhibition of ROS formation during glycation. (2) Inhibition of Schiff base, Amadori products, and subsequent dicarbonyl groups formation. (3) Detoxification of AGE precursor-MG by glyoxalase system. (4) Inhibition of harmful AGEs formation. (5) Blocking of AGE–RAGE interaction inhibits oxidative stress and ROS generation, inflammatory stimuli, and physical injury through different pathways. AGE=advanced glycation end product; GLO=glyoxalase; MG=methylglyoxal; RAGE=receptor of AGEs; ROS=reactive oxygen species.