Protective Effects of Swertiamarin against Methylglyoxal-Induced Epithelial-Mesenchymal Transition by Improving Oxidative Stress in Rat Kidney Epithelial (NRK-52E) Cells.

Kirti Parwani,Palash Mandal,Dhara Patel,Farhin Patel

doi:10.3390/molecules26092748

Kirti Parwani, Palash Mandal + Show 2 more

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https://doi.org/10.3390/molecules26092748

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Abstract

Increased blood glucose in diabetic individuals results in the formation of advanced glycation end products (AGEs), causing various adverse effects on kidney cells, thereby leading to diabetic nephropathy (DN). In this study, the antiglycative potential of Swertiamarin (SM) isolated from the methanolic extract of E. littorale was explored. The effect of SM on protein glycation was studied by incubating bovine serum albumin with fructose at 60 °C in the presence and absence of different concentrations of swertiamarin for 24 h. For comparative analysis, metformin was also used at similar concentrations as SM. Further, to understand the role of SM in preventing DN, in vitro studies using NRK-52E cells were done by treating cells with methylglyoxal (MG) in the presence and absence of SM. SM showed better antiglycative potential as compared to metformin. In addition, SM could prevent the MG mediated pathogenesis in DN by reducing levels of argpyrimidine, oxidative stress and epithelial mesenchymal transition in kidney cells. SM also downregulated the expression of interleukin-6, tumor necrosis factor-α and interleukin-1β. This study, for the first time, reports the antiglycative potential of SM and also provides novel insights into the molecular mechanisms by which SM prevents toxicity of MG on rat kidney cells.

Highlights

Type 2 Diabetes (T2D) is a metabolic syndrome, which results due to peripheral insulin resistance, affecting both metabolism and the disposal of glucose
The treatment of the NRK-52E cells with MG leads to the production of advanced glycation end products (AGEs) which
bovine serum albumin (BSA) glycated with fructose showed increased fluorescence intensity as compared to BSA treated with fructose in the presence of SM, which explains the role of SM in being able to prevent the formation of AGEs

Summary

Introduction

Type 2 Diabetes (T2D) is a metabolic syndrome, which results due to peripheral insulin resistance, affecting both metabolism and the disposal of glucose. Elevated blood glucose, which induces reactive oxygen species (ROS) formation, is understood to be one of the main reasons for the formation of advanced glycation end products (AGEs) in the intracellular and extracellular environment [4]. AGEs are the products of nonenzymatic glycation between free amino acids and reducing sugar via the Maillard reaction resulting into yellowish-brown fluorescent and insoluble adducts. Amadori product, a stable compound is formed from an unstable Schiff base [5]. Amadori products can either form reactive dicarbonyls like glyoxal and methylglyoxal (MG) or undergo various chemical reactions like condensation, dehydration and oxidation to form AGEs

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