Isosamidin fromPeucedanum japonicumRoots 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, cardiovascular diseases, and atherosclerosis. In this study, the protective effect of isosamidin, isolated fromPeucedanum japonicumroots, on MGO-induced apoptosis was investigated using human umbilical vein endothelial cells (HUVECs). Among the 20 compounds isolated fromP. 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 fromP. japonicummay 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.