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.

Highlights

  • Advanced glycation end products (AGEs) are generated via the Maillard reaction, in which non-enzymatic glycation occurs between reducing sugars and amine residues on proteins, lipids, or nucleic acids [1,2]

  • Our results showed that peanut extracts containing various phenolics that can decrease AGEs and alleviate MGO-mediated apoptosis in human umbilical vein endothelial cells (HUVECs) by regulating mitogen-activated protein kinases (MAPKs), Bcl-2 family members, and reactive oxygen species (ROS) generation

  • We confirmed that phenolic-rich peanut extracts inhibit AGE formation in the presence of MGO or GO, and possess the ability to break preformed AGEs

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Summary

Introduction

Advanced glycation end products (AGEs) are generated via the Maillard reaction, in which non-enzymatic glycation occurs between reducing sugars and amine residues on proteins, lipids, or nucleic acids [1,2]. The major AGEs appear to be derived from the highly reactive intermediate. Nutrients 2017, 9, 1214 carbonyl compounds dicarbonyls and oxoaldehydes, including 3-deoxyglucosone, glyoxal (GO), and methylglyoxal (MGO) [3]. Collagen-linked AGEs initiate oxidative reactions and interact with endothelial cells, thereby leading to vascular dysfunction [4]. Endothelial dysfunction plays a role in the development of atherosclerosis and diabetic vascular disease [5]. AGE accumulation is considered to be associated with the development of diabetic complications. Phenolic compounds generated as secondary metabolites in plants play protective roles against

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