Dieckol, Derived from the Edible Brown Algae <i>Ecklonia cava,</i> Attenuates Methylglyoxal-Associated Diabetic Nephropathy by Suppressing AGE–RAGE Interaction
The formation of advanced glycation end products (AGE) is linked to the pathogenesis of diabetic nephropathy. The aim of this work was to assess the therapeutic potential and underlying mechanism of action of dieckol (DK), isolated from <i>Ecklonia cava</i>, on renal damage induced by me...
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MDPI AG
2023-02-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/3/593 |
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| author | Chi-Heung Cho Guijae Yoo Mingyeong Kim Ulfah Dwi Kurniawati In-Wook Choi Sang-Hoon Lee |
| author_facet | Chi-Heung Cho Guijae Yoo Mingyeong Kim Ulfah Dwi Kurniawati In-Wook Choi Sang-Hoon Lee |
| author_sort | Chi-Heung Cho |
| collection | DOAJ |
| description | The formation of advanced glycation end products (AGE) is linked to the pathogenesis of diabetic nephropathy. The aim of this work was to assess the therapeutic potential and underlying mechanism of action of dieckol (DK), isolated from <i>Ecklonia cava</i>, on renal damage induced by methylglyoxal (MGO) in mouse glomerular mesangial cells. The antiglycation properties of DK were evaluated using ELISA. We conducted molecular docking, immunofluorescence analysis, and Western blotting to confirm the mechanism by which DK prevents AGE-related diabetic nephropathy. DK treatment exhibited antiglycation properties through the inhibition of AGE production, inhibition of cross-linking between AGE and collagen, and breaking of its cross-linking. DK pretreatment exhibited protective effects on renal cells by suppressing MGO-induced intracellular reactive oxygen species (ROS) formation, intracellular MGO and AGE accumulation, activation of the apoptosis cascade and apoptosis-related protein expression, activation of receptor for AGE (RAGE) protein expression, and suppression of the glyoxalase system. Furthermore, DK exhibited a stronger binding affinity for RAGE than AGE, which was confirmed as exerting a competitive inhibitory effect on the AGE–RAGE interaction. These results demonstrated that DK is a potential natural AGE inhibitor that can be utilized to prevent and treat AGE-induced diabetic nephropathy. |
| first_indexed | 2024-03-11T07:00:57Z |
| format | Article |
| id | doaj.art-d64c2d93a148408dad44e8f81d707aa0 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-11T07:00:57Z |
| publishDate | 2023-02-01 |
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| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-d64c2d93a148408dad44e8f81d707aa02023-11-17T09:16:57ZengMDPI AGAntioxidants2076-39212023-02-0112359310.3390/antiox12030593Dieckol, Derived from the Edible Brown Algae <i>Ecklonia cava,</i> Attenuates Methylglyoxal-Associated Diabetic Nephropathy by Suppressing AGE–RAGE InteractionChi-Heung Cho0Guijae Yoo1Mingyeong Kim2Ulfah Dwi Kurniawati3In-Wook Choi4Sang-Hoon Lee5Division of Functional Food Research, Korea Food Research Institute, Wanju 55365, Republic of KoreaDivision of Functional Food Research, Korea Food Research Institute, Wanju 55365, Republic of KoreaDepartment of Food Biotechnology, University of Science and Technology, Daejeon 34113, Republic of KoreaDepartment of Food Biotechnology, University of Science and Technology, Daejeon 34113, Republic of KoreaDivision of Functional Food Research, Korea Food Research Institute, Wanju 55365, Republic of KoreaDivision of Functional Food Research, Korea Food Research Institute, Wanju 55365, Republic of KoreaThe formation of advanced glycation end products (AGE) is linked to the pathogenesis of diabetic nephropathy. The aim of this work was to assess the therapeutic potential and underlying mechanism of action of dieckol (DK), isolated from <i>Ecklonia cava</i>, on renal damage induced by methylglyoxal (MGO) in mouse glomerular mesangial cells. The antiglycation properties of DK were evaluated using ELISA. We conducted molecular docking, immunofluorescence analysis, and Western blotting to confirm the mechanism by which DK prevents AGE-related diabetic nephropathy. DK treatment exhibited antiglycation properties through the inhibition of AGE production, inhibition of cross-linking between AGE and collagen, and breaking of its cross-linking. DK pretreatment exhibited protective effects on renal cells by suppressing MGO-induced intracellular reactive oxygen species (ROS) formation, intracellular MGO and AGE accumulation, activation of the apoptosis cascade and apoptosis-related protein expression, activation of receptor for AGE (RAGE) protein expression, and suppression of the glyoxalase system. Furthermore, DK exhibited a stronger binding affinity for RAGE than AGE, which was confirmed as exerting a competitive inhibitory effect on the AGE–RAGE interaction. These results demonstrated that DK is a potential natural AGE inhibitor that can be utilized to prevent and treat AGE-induced diabetic nephropathy.https://www.mdpi.com/2076-3921/12/3/593dieckolreceptor for advanced glycation end productmolecular dockingmethylglyoxaldiabetic nephropathybrown seaweed |
| spellingShingle | Chi-Heung Cho Guijae Yoo Mingyeong Kim Ulfah Dwi Kurniawati In-Wook Choi Sang-Hoon Lee Dieckol, Derived from the Edible Brown Algae <i>Ecklonia cava,</i> Attenuates Methylglyoxal-Associated Diabetic Nephropathy by Suppressing AGE–RAGE Interaction Antioxidants dieckol receptor for advanced glycation end product molecular docking methylglyoxal diabetic nephropathy brown seaweed |
| title | Dieckol, Derived from the Edible Brown Algae <i>Ecklonia cava,</i> Attenuates Methylglyoxal-Associated Diabetic Nephropathy by Suppressing AGE–RAGE Interaction |
| title_full | Dieckol, Derived from the Edible Brown Algae <i>Ecklonia cava,</i> Attenuates Methylglyoxal-Associated Diabetic Nephropathy by Suppressing AGE–RAGE Interaction |
| title_fullStr | Dieckol, Derived from the Edible Brown Algae <i>Ecklonia cava,</i> Attenuates Methylglyoxal-Associated Diabetic Nephropathy by Suppressing AGE–RAGE Interaction |
| title_full_unstemmed | Dieckol, Derived from the Edible Brown Algae <i>Ecklonia cava,</i> Attenuates Methylglyoxal-Associated Diabetic Nephropathy by Suppressing AGE–RAGE Interaction |
| title_short | Dieckol, Derived from the Edible Brown Algae <i>Ecklonia cava,</i> Attenuates Methylglyoxal-Associated Diabetic Nephropathy by Suppressing AGE–RAGE Interaction |
| title_sort | dieckol derived from the edible brown algae i ecklonia cava i attenuates methylglyoxal associated diabetic nephropathy by suppressing age rage interaction |
| topic | dieckol receptor for advanced glycation end product molecular docking methylglyoxal diabetic nephropathy brown seaweed |
| url | https://www.mdpi.com/2076-3921/12/3/593 |
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