1. Introduction
Hyperglycemia, prediabetes, diabetes, inflammation, hyperglycemia, prediabetic, causes cell damage
HYPERGLYCEMIA, VASCULAR COMPLICATIONS, INFLAMMATION, DIABETES MELLITUS, HYPERGLYCEMIA, OXIDATIVE STRESS, DISEASES, COMPLICATIONS, ENDOTHELIAL DYSFUNCTION
The most significant reactive α-dicarbonyl RCS involved in the pathomechanism of glycation and related diseases is methylglyoxal (MGO). Hyperglycemia promotes the generation of MGO and leads to the formation of advanced glycation end products (AGEs). Therefore, MGO trapping and glycation inhibition appear to be important therapeutic targets in prediabetes, diabetes, and in the early prevention of hyperglycemic complications. Peppermint leaf is commonly used as herbal tea, rich in polyphenols. Eriocitrin, its predominant component, in a double-blind, randomized controlled study reversed the prediabetic condition in patients. However, the antiglycation activity of this plant material and its polyphenols has not been characterized to date. Therefore, the aim of this study was to evaluate the ability of a peppermint leaf dry extract and its polyphenols to inhibit non-enzymatic protein glycation in a model with bovine serum albumin (BSA) and MGO as a glycation agent. Peppermint polyphenols were also evaluated for their potential to trap MGO in vitro, and the resulting adducts were analyzed by UHPLC-ESI-MS. To relate chemical composition to glycation inhibitory activity, the obtained peppermint extract was subjected to qualitative and quantitative analysis. The capability of peppermint leaf polyphenols to inhibit glycation (27.3–77.2%) and form adducts with MGO was confirmed. In the case of flavone aglycones, mono- and di-adducts with MGO were observed, while eriodictyol and eriocitrin effectively produced only mono-adducts. Rosmarinic acid and luteolin-7-Non-enzymatic glycation is a reaction between the carbonyl groups of reducing sugars or their derivatives such as reactive carbonyl species (RCS) and the amino, guanidino, or thiol groups of some biomolecules including peptides, proteins, lipoproteins, and nucleic acids. Several physiological products of sugar autooxidation are known, as well as intermediates from glucose and fructose metabolism characterized by the presence of two adjacent carbonyl groups (α-dicarbonyl compounds). These compounds are ketoaldehydes or dialdehydes and are currently called RCS due to their high reactivity. The most important ketoaldehyde involved in the pathomechanism of non-enzymatic glycation and related diseases is methylglyoxal (MGO). Long-term hyperglycemia promotes the production of MGO, and this significantly increases glycation, leading, among other things, to the formation of irreversible advanced glycation end products (AGEs). AGEs can bind to specific receptors (RAGE) in the cell membrane and consequently trigger the nuclear factor κB (NF-κB) signaling pathway, which induces inflammation and oxidative stress and causes cell damage. In patients with diabetes mellitus, blood proteins such as hemoglobin and serum albumin are particularly vulnerable to glycation. MGO-derived AGEs have been shown to play a pivotal role in the onset and progression of vascular complications of diabetics. Methylglyoxal thus appears to be a significant contributor to endothelial dysfunction by increasing oxidation, as well as inducing inflammation and apoptosis [Several substances of natural origin that can inhibit non-enzymatic protein glycation in the BSA-methylglyoxal and BSA-glucose systems are known. Such potential has been described, among others, for the polyphenols of rooibos, green and black tea [Peppermint (The diverse chemical composition of Therefore, the aim of our study was to evaluate the ability to inhibit the process of non-enzymatic protein glycation by a peppermint leaf dry extract and its major polyphenolic components in a model with bovine serum albumin and methylglyoxal as a glycation agent. Peppermint polyphenols were also evaluated for their potential to capture MGO in vitro, and the resulting adducts were analyzed by UHPLC-ESI-MS. The effect of individual extract components on the observed antiglycation properties was also investigated.