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Open AccessArticle

Isosamidin from Peucedanum japonicum Roots Prevents Methylglyoxal-Induced Glucotoxicity in Human Umbilical Vein Endothelial Cells via Suppression of ROS-Mediated Bax/Bcl-2

1
Korea Food Research Institute, 245, Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365, Korea
2
College of Pharmacy, Gachon University, #191, Hambakmoero, Yeonsu-gu, Incheon 21936, Korea
3
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea
4
Gachon Institute of Pharmaceutical Science, Gachon University; #191, Hambakmoe-ro, Yeonsu-gu, Incheon 21936, Korea
5
Gachon Medical Research Institute, Gil Medical Center, Inchon 21565, Korea
*
Author to whom correspondence should be addressed.
The authors contributed equally to this work.
Antioxidants 2020, 9(6), 531; https://doi.org/10.3390/antiox9060531
Received: 14 May 2020 / Revised: 9 June 2020 / Accepted: 15 June 2020 / Published: 17 June 2020
(This article belongs to the Special Issue Oxidative Stress and Inflammation in Cardiovascular Diseases)
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 Peucedanum japonicum roots, on MGO-induced apoptosis was investigated using human umbilical vein endothelial cells (HUVECs). Among the 20 compounds isolated from P. japonicum, 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 P. japonicum 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. View Full-Text
Keywords: methylglyoxal; reactive oxygen species; human umbilical vein endothelial cells; Peucedanum japonicum; isosamidin; mitogen-activated protein kinases; advanced glycation end products; endothelial dysfunction methylglyoxal; reactive oxygen species; human umbilical vein endothelial cells; Peucedanum japonicum; isosamidin; mitogen-activated protein kinases; advanced glycation end products; endothelial dysfunction
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MDPI and ACS Style

Do, M.H.; Lee, J.H.; Ahn, J.; Hong, M.J.; Kim, J.; Kim, S.Y. Isosamidin from Peucedanum japonicum Roots Prevents Methylglyoxal-Induced Glucotoxicity in Human Umbilical Vein Endothelial Cells via Suppression of ROS-Mediated Bax/Bcl-2. Antioxidants 2020, 9, 531.

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