Abstract

Vascular endothelial dysfunction can be induced by homocysteine (Hcy) through promoted oxidative stress. Huang Qi decoction (HQD) is a traditional Chinese medical formula and its components possess antioxidant effect. The study herein was therefore designed to investigate the effects of HQD at different dosage on endothelial dysfunction induced by Hcy. Tempol and apocynin were used to investigate whether antioxidant mechanisms were involved. Endothelium-dependent relaxation of rat aortas was investigated by isometric tension recordings. Reactive oxygen species (ROS) in human umbilical vein endothelial cells (HUVECs) was determined by DHE staining. The assessment related to oxidative stress and NO bioavailability was performed by assay kits and western blot. In isometric tension experiment, HQD at the dose of 30 or 100 μg/mL, tempol, or apocynin prevented impaired endothelium-dependent relaxation in isolated aortas elicited by Hcy. In cellular experiments, substantial enhancement in NADPH oxidase and ROS generation and reduction in NO bioavailability triggered by Hcy were reversed by pretreatment of HQD at the dose of 100 μg/mL, tempol, or apocynin. The results proved that HQD at an appropriate dosage presented favorable effects on endothelial dysfunction initiated by Hcy through antioxidant mechanisms. HQD can act as a potent prescription for the treatment of endothelium related vascular complications.

Highlights

  • Endothelial dysfunction, featured by an impaired endothelium-dependent vasodilatation, has been considered to be involved in the pathogenesis of diabetes mellitus and related vascular complications [1]

  • Antibodies of p47phox, p67phox, p40phox, p22phox, and gp91phox were from Santa Cruz Biotechnology (Santa Cruz, CA, USA); Ras-1 and β-actin were obtained from Cell Signaling Technology (Danvers, MA, USA); endothelial NO synthase (eNOS) and p-eNOS were provided by Abcam (Cambridge, MA, USA)

  • To determine whether increasing NO production is involved in the protective effect of Huang Qi decoction (HQD), tempol, and apocynin on impaired endothelium-dependent relaxation induced by Hcy, aortic rings were pretreated with L-NAME (100 μM, 30 min) before PE-induced contraction

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Summary

Introduction

Endothelial dysfunction, featured by an impaired endothelium-dependent vasodilatation, has been considered to be involved in the pathogenesis of diabetes mellitus and related vascular complications [1]. Decreasing ROS in endothelial cells offers an appealing strategy to normalize Hcy-induced impaired endothelium-dependent vasomotor response and endothelial dysfunction. Huang Qi decoction (HQD) is a classic traditional Chinese medical formulation consisting of various medicinal herbs, which is first described thousands of years ago. It is comprised of Astragalus (Huang Qi), Poria (Fu Ling), Trichosanthes (Gua Lou), Ophiopogon (Mai Dong), Schisandra (Wu Wei Zi), licorice (Gan Cao), and Rehmannia (Di Huang). We investigate the effects of HQD on endothelium-dependent aortic vasorelaxation and endothelial ROS generation induced by Hcy, determining whether the antioxidant mechanism is involved in the beneficial effects of HQD against Hcyinduced endothelial dysfunction

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