Inhibitory Effect of Arachis hypogaea (Peanut) and Its Phenolics against Methylglyoxal-Derived Advanced Glycation End Product Toxicity

Abstract

Methylglyoxal (MGO) is a highly reactive dicarbonyl compound that causes endothelial dysfunction and plays important roles in the development of diabetic complications. Peanuts are rich in energy, minerals, and antioxidants. Here, we report the potential beneficial effects of peanuts, and particularly the phenolic contents, against MGO-mediated cytotoxicity. Firstly, we optimized the extraction conditions for maximum yield of phenolics from peanuts by examining different processing methods and extraction solvents. To estimate the phenolic contents of peanut extracts, a simultaneous analysis method was developed and validated by ultra-high-performance liquid chromatography-tandem mass spectrometry. We found that roasted peanuts and their 80% methanol extracts showed the highest amount of total phenolics. Secondly, we evaluated the inhibitory effects of phenolics and peanut extracts against MGO-mediated cytotoxicity. Phenolics and peanut extracts were observed to inhibit advanced glycation end product (AGE) formation as well as to break preformed AGEs. Furthermore, pretreatment with peanut extracts significantly inhibited MGO-induced cell death and reactive oxygen species production in human umbilical vein endothelial cells. Peanut extracts prevented MGO-induced apoptosis by increasing Bcl-2 expression and decreasing Bax expression, and MGO-mediated activation of mitogen-activated protein kinases (MAPKs). In conclusion, the constituents of peanuts may prevent endothelial dysfunction and diabetic complications.