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

• Published in: Antioxidants Vol. 9; no. 6; p. 531
• Main Authors: Do, Moon Ho, Lee, Jae Hyuk, Ahn, Jongmin, Hong, Min Jee, Kim, Jinwoong, Kim, Sun Yeou
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 17.06.2020; MDPI
• Subjects: Advanced glycosylation end products; Apoptosis; Arteriosclerosis; BAX protein; Bcl-2 protein; Biotechnology; c-Jun protein; Cardiovascular diseases; Cell death; Cytotoxicity; Diabetes; Diabetes mellitus; Endothelial cells; Extracellular signal-regulated kinase; Flow cytometry; Glycosylation; Health aspects; human umbilical vein endothelial cells; isosamidin; JNK protein; Kinases; Metabolites; methylglyoxal; Mitogen-activated protein kinases; Peucedanum; Peucedanum japonicum; Proteins; Pyruvaldehyde; Reactive oxygen species; Roots; Rosidae; Transcription factors; Umbilical vein; South Korea; United States > US
• ISSN: 2076-3921; 2076-3921
• DOI: 10.3390/antiox9060531

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.