Sanguis draconis, a dragon's blood resin, attenuates high glucose-induced oxidative stress and endothelial dysfunction in human umbilical vein endothelial cells.

Thanasekaran Jayakumar,Cheuk-Sing Choy,Yi Chang,Jie-Jen Lee,Yung-Kai Huang,Ting-Chen Chang,Nen-Chung Chang

doi:10.1155/2014/423259

Abstract

Hyperglycaemia, a characteristic feature of diabetes mellitus, induces endothelial dysfunction and vascular complications by limiting the proliferative potential of these cells. Here we aimed to investigate the effect of an ethanolic extract of Sanguis draconis (SD), a kind of dragon's blood resin that is obtained from Daemonorops draco (Palmae), on human umbilical vein endothelial cells (HUVEC) under high-glucose (HG) stimulation and its underlying mechanism. Concentration-dependent (0–50 μg/mL) assessment of cell viability showed that SD does not affect cell viability with a similar trend up to 48 h. Remarkably, SD (10–50 μg/mL) significantly attenuated the high-glucose (25 and 50 mM) induced cell toxicity in a concentration-dependent manner. SD inhibited high glucose-induced nitrite (NO) and lipid peroxidation (MDA) production and reactive oxygen species (ROS) formation in HUVEC. Western blot analysis revealed that SD treatments abolished HG-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK 1/2), nuclear transcription factor, κB (NF-κB), VCAM-1, and E-selectin, and it also blocked the breakdown of PARP-116 kDa protein in a dose-dependent manner. Furthermore, we found that SD increased the expression of Bcl-2 and decreased Bax protein expression in HG-stimulated HUVEC. Thus, these results of this study demonstrate for the first time that SD inhibits glucose induced oxidative stress and vascular inflammation in HUVEC by inhibiting the ERK/NF-κB/PARP-1/Bax signaling cascade followed by suppressing the activation of VCAM-1 and E-selectin. These data suggest that SD may have a therapeutic potential in vascular inflammation due to the decreased levels of oxidative stress, apoptosis, and PARP-1 activation.

Highlights

Vascular disorders through overexpression of adhesion molecules are thought to play in the pathogenesis of atherosclerosis
We postulated that Sanguis draconis (SD) can retreat the effects induced by high glucose concentration in endothelial cells; we evaluated the effect of SD on reactive oxygen species (ROS), nitric oxide (NO), and MDA production and expression of adhesion molecules nuclear transcription factor-κB (NF-κB), Poly (ADP-ribose) polymerase (PARP)-1, ERK, and on Bax-Bcl2 in human umbilical vein endothelial cells (HUVEC) treated with high concentrations of glucose
We evaluated the protective effect of Sanguis draconis (SD), a kind of red resin, against the dysfunction and activation of endothelial cells induced by high concentrations of glucose

Summary

Introduction

Vascular disorders through overexpression of adhesion molecules are thought to play in the pathogenesis of atherosclerosis. Adhesion molecules are proteins which regulate the interaction between endothelium and leukocytes. An increase in their expression on the endothelial surface causes increased adhesion of leukocytes. Endothelial cells in human atherosclerotic lesions have been shown to overexpress intercellular adhesion molecule-1 (ICAM-1), vascular cell. NF-κB is present in the cytoplasm as an inactive form bound to its inhibitor molecule, inhibitory factor of NF-κB-α (IκB-α). During the oxidative stress, endothelial cells generate ROS, such as superoxides and peroxynitrite, leading to low-density lipo protein (LDL) oxidation, and the formation of ROS together with inflammatory factors including chemokines, cytokines, and adhesion molecules has been shown to be increased in atherosclerotic lesions [3]. ROS can modify endothelial function by a variety of mechanisms, such as peroxidation of membrane lipids, activation of NF-κB, and decreasing the availability of nitric oxide (NO) [5]

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