Isosamidin from <i>Peucedanum japonicum</i> Roots Prevents Methylglyoxal-Induced Glucotoxicity in Human Umbilical Vein Endothelial Cells via Suppression of ROS-Mediated Bax/Bcl-2
Methylglyoxal (MGO) is a highly reactive metabolite of glucose. Elevated levels of MGO induce the generation of reactive oxygen species (ROS) and cause cell death in endothelial cells. Vascular endothelial cell damage by ROS has been implicated in the progression of diabetic vascular complications,...
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MDPI AG
2020-06-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/9/6/531 |
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| author | Moon Ho Do Jae Hyuk Lee Jongmin Ahn Min Jee Hong Jinwoong Kim Sun Yeou Kim |
| author_facet | Moon Ho Do Jae Hyuk Lee Jongmin Ahn Min Jee Hong Jinwoong Kim Sun Yeou Kim |
| author_sort | Moon Ho Do |
| collection | DOAJ |
| description | Methylglyoxal (MGO) is a highly reactive metabolite of glucose. Elevated levels of MGO induce the generation of reactive oxygen species (ROS) and cause cell death in endothelial cells. Vascular endothelial cell damage by ROS has been implicated in the progression of diabetic vascular complications, cardiovascular diseases, and atherosclerosis. In this study, the protective effect of isosamidin, isolated from <i>Peucedanum japonicum</i> roots, on MGO-induced apoptosis was investigated using human umbilical vein endothelial cells (HUVECs). Among the 20 compounds isolated from <i>P. japonicum</i>, isosamidin showed the highest effectiveness in inhibiting MGO-induced apoptosis of HUVECs. Pretreatment of HUVECs with isosamidin significantly prevented the generation of ROS and cell death induced by MGO. Isosamidin prevented MGO-induced apoptosis in HUVECs by downregulating the expression of Bax and upregulating the expression of Bcl-2. MGO treatment activated mitogen-activated protein kinases (MAPKs), such as p38, c-Jun N terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). In contrast, pretreatment with isosamidin strongly inhibited the activation of p38 and JNK. Furthermore, isosamidin caused the breakdown of the crosslinks of the MGO-derived advanced glycation end products (AGEs). These findings suggest that isosamidin from <i>P. japonicum</i> may be used as a preventive agent against MGO-mediated endothelial dysfunction in diabetes. However, further study of the therapeutic potential of isosamidin on endothelial dysfunction needs to explored in vivo models. |
| first_indexed | 2024-03-10T19:05:48Z |
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| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T19:05:48Z |
| publishDate | 2020-06-01 |
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| series | Antioxidants |
| spelling | doaj.art-12da75ef941d4d5384da435c0bbc020f2023-11-20T04:09:10ZengMDPI AGAntioxidants2076-39212020-06-019653110.3390/antiox9060531Isosamidin from <i>Peucedanum japonicum</i> Roots Prevents Methylglyoxal-Induced Glucotoxicity in Human Umbilical Vein Endothelial Cells via Suppression of ROS-Mediated Bax/Bcl-2Moon Ho Do0Jae Hyuk Lee1Jongmin Ahn2Min Jee Hong3Jinwoong Kim4Sun Yeou Kim5Korea Food Research Institute, 245, Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365, KoreaCollege of Pharmacy, Gachon University, #191, Hambakmoero, Yeonsu-gu, Incheon 21936, KoreaCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, KoreaCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, KoreaCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, KoreaCollege of Pharmacy, Gachon University, #191, Hambakmoero, Yeonsu-gu, Incheon 21936, KoreaMethylglyoxal (MGO) is a highly reactive metabolite of glucose. Elevated levels of MGO induce the generation of reactive oxygen species (ROS) and cause cell death in endothelial cells. Vascular endothelial cell damage by ROS has been implicated in the progression of diabetic vascular complications, cardiovascular diseases, and atherosclerosis. In this study, the protective effect of isosamidin, isolated from <i>Peucedanum japonicum</i> roots, on MGO-induced apoptosis was investigated using human umbilical vein endothelial cells (HUVECs). Among the 20 compounds isolated from <i>P. japonicum</i>, isosamidin showed the highest effectiveness in inhibiting MGO-induced apoptosis of HUVECs. Pretreatment of HUVECs with isosamidin significantly prevented the generation of ROS and cell death induced by MGO. Isosamidin prevented MGO-induced apoptosis in HUVECs by downregulating the expression of Bax and upregulating the expression of Bcl-2. MGO treatment activated mitogen-activated protein kinases (MAPKs), such as p38, c-Jun N terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). In contrast, pretreatment with isosamidin strongly inhibited the activation of p38 and JNK. Furthermore, isosamidin caused the breakdown of the crosslinks of the MGO-derived advanced glycation end products (AGEs). These findings suggest that isosamidin from <i>P. japonicum</i> may be used as a preventive agent against MGO-mediated endothelial dysfunction in diabetes. However, further study of the therapeutic potential of isosamidin on endothelial dysfunction needs to explored in vivo models.https://www.mdpi.com/2076-3921/9/6/531methylglyoxalreactive oxygen specieshuman umbilical vein endothelial cells<i>Peucedanum japonicum</i>isosamidinmitogen-activated protein kinases |
| spellingShingle | Moon Ho Do Jae Hyuk Lee Jongmin Ahn Min Jee Hong Jinwoong Kim Sun Yeou Kim Isosamidin from <i>Peucedanum japonicum</i> Roots Prevents Methylglyoxal-Induced Glucotoxicity in Human Umbilical Vein Endothelial Cells via Suppression of ROS-Mediated Bax/Bcl-2 Antioxidants methylglyoxal reactive oxygen species human umbilical vein endothelial cells <i>Peucedanum japonicum</i> isosamidin mitogen-activated protein kinases |
| title | Isosamidin from <i>Peucedanum japonicum</i> Roots Prevents Methylglyoxal-Induced Glucotoxicity in Human Umbilical Vein Endothelial Cells via Suppression of ROS-Mediated Bax/Bcl-2 |
| title_full | Isosamidin from <i>Peucedanum japonicum</i> Roots Prevents Methylglyoxal-Induced Glucotoxicity in Human Umbilical Vein Endothelial Cells via Suppression of ROS-Mediated Bax/Bcl-2 |
| title_fullStr | Isosamidin from <i>Peucedanum japonicum</i> Roots Prevents Methylglyoxal-Induced Glucotoxicity in Human Umbilical Vein Endothelial Cells via Suppression of ROS-Mediated Bax/Bcl-2 |
| title_full_unstemmed | Isosamidin from <i>Peucedanum japonicum</i> Roots Prevents Methylglyoxal-Induced Glucotoxicity in Human Umbilical Vein Endothelial Cells via Suppression of ROS-Mediated Bax/Bcl-2 |
| title_short | Isosamidin from <i>Peucedanum japonicum</i> Roots Prevents Methylglyoxal-Induced Glucotoxicity in Human Umbilical Vein Endothelial Cells via Suppression of ROS-Mediated Bax/Bcl-2 |
| title_sort | isosamidin from i peucedanum japonicum i roots prevents methylglyoxal induced glucotoxicity in human umbilical vein endothelial cells via suppression of ros mediated bax bcl 2 |
| topic | methylglyoxal reactive oxygen species human umbilical vein endothelial cells <i>Peucedanum japonicum</i> isosamidin mitogen-activated protein kinases |
| url | https://www.mdpi.com/2076-3921/9/6/531 |
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