Therapeutic Potential of Phlorotannin-Rich Ecklonia cava Extract on Methylglyoxal-Induced Diabetic Nephropathy in In Vitro Model |
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Authors: | Chi-Heung Cho Chang-Jun Lee Min-Gyeong Kim Bomi Ryu Jun-Geon Je Yoonsook Kim Sang-Hoon Lee |
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Institution: | 1.Division of Functional Food Research, Korea Food Research Institute, Wanju 55365, Korea; (C.-H.C.); (C.-J.L.); (M.-G.K.); (Y.K.);2.Department of Food Science and Technology, Chonbuk National University, Jeonju 54896, Korea;3.Department of Food Biotechnology, University of Science and Technology, Daejeon 34113, Korea;4.Marine Science Institute, Jeju National University, Jeju 63333, Korea; (B.R.); (J.-G.J.) |
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Abstract: | Advanced glycation end-products (AGEs) play a vital role in the pathogenesis of diabetic complications. Methylglyoxal (MGO), one of the major precursors of AGEs, is a highly reactive dicarbonyl compound that plays an important role in the pathogenesis of diabetic nephropathy. This study was designed to evaluate the therapeutic potential of phlorotannin-rich Ecklonia cava extract (ECE) on MGO-induced diabetic nephropathy in in vitro models using mouse glomerular mesangial cells. ECE showed anti-glycation activity via breaking of AGEs-collagen cross-links and inhibition of AGEs formation and AGE-collagen cross-linking formation. The renoprotective effects were determined by assessing intracellular reactive oxygen species (ROS) and MGO accumulation, cell apoptosis, and the Nrf-2/ARE signaling pathway. MGO-induced renal damage, intracellular ROS production level, and MGO-protein adduct accumulation were significantly decreased by pretreating ECE. Moreover, ECE pretreatment exhibited preventive properties against MGO-induced dicarbonyl stress via activation of the Nrf2/ARE signaling pathway and reduction of RAGE protein expression in mouse glomerular mesangial cells. Collectively, these results indicated potential anti-glycation properties and prominent preventive effects of ECE against MGO-induced renal damage. Additionally, ECE may be utilized for the management of AGE-related diabetic nephropathy. |
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Keywords: | Ecklonia cava phlorotannin diabetic nephropathy advanced glycation end-products methylglyoxal mouse glomerular mesangial cell RAGE apoptosis Nrf2/ARE signaling pathway MAPK signaling pathway |
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