Endothelium-Dependent Relaxation Effect of Apocynum venetum Leaf Extract via Src/PI3K/Akt Signalling Pathway.

Yeh Lau,Mohd Mustafa,Chiu Kwan,Dharmani Murugan,Wei Ling

doi:10.3390/nu7075220

Yeh Lau, Mohd Mustafa + Show 3 more

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https://doi.org/10.3390/nu7075220

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Journal: Nutrients	Publication Date: Jun 30, 2015
Citations: 43	License type: CC BY 4.0

Affiliation: University of Malaya

Abstract

Botanical herbs are consumed globally not only as an essential diet but also as medicines or as functional/recreational food supplements. The extract of the Apocynum venetum leaves (AVLE), also known as Luobuma, exerts its antihypertensive effect via dilating the blood vessels in an endothelium- and concentration-dependent manner with optimal effect seen at as low as 10 µg/mL. A commercial Luoboma “antihypertensive tea” is available commercially in the western province of China. The present study seeks to investigate the underlying cellular mechanisms of the nitric oxide (NO)-releasing property of AVLE in rat aortas and human umbilical vein endothelial cells (HUVECs). Endothelium-dependent relaxation induced by AVLE was assessed in organ chambers in the presence or absence of polyethyleneglycol catalase (PP2, 20 µM; inhibitor of Src kinase), wortmannin (30 nM) and LY294002 (20 µM; PI3 (phosphatidylinositol3)-Kinase inhibitor), NG-nitro-l-arginine (L-NAME, 100 µM; endothelial NO synthase inhibitor (eNOS)) and ODQ (1 µM; soluble guanylyl cyclase inhibitor). Total nitrite and nitrate (NOx) level and protein expression of p-Akt and p-eNOS were measured. AVLE-induced endothelium-dependent relaxation was reduced by PP2, wortmannin and LY294002 and abolished by L-NAME and ODQ. AVLE significantly increased total NOx level in rat aortas and in HUVECs compared to control. It also instigated phosphorylation of Akt and eNOS in cultured HUVECs in a concentration-dependent manner and this was markedly suppressed by PP2, wortmannin and LY294002. AVLE also inhibited superoxide generated from both NADPH oxidase and xanthine/xanthine oxidase system. Taken together, AVLE causes endothelium-dependent NO mediated relaxations of rat aortas through Src/PI3K/Akt dependent NO signalling pathway and possesses superoxide scavenging activity.

Highlights

Hypertension, a cardiovascular disease with increased arterial pressure and increased vascular resistance, is a major contributor to morbidity and mortality [1]
The elevated level of nitric oxide (NO) induced by Apocynum venetum leaves (AVLE) was remarkably inhibited by PP2, wortmannin and LY294002 (Figure 2)
Cell-free-mediated superoxide generation system, we further demonstrated that inhibited the enzymatic production of superoxide production system, we further demonstrated that AVLE inhibited the enzymatic production of superoxide in production the X/xanthine oxidase (XO) in cell-free system

Summary

Introduction

Hypertension, a cardiovascular disease with increased arterial pressure and increased vascular resistance, is a major contributor to morbidity and mortality [1]. In addition to reducing blood pressure, TCM herbs are often used for the relief of symptoms related to cardiac problems and stroke, removing blood stagnation, reversing vascular remodelling and improving endothelium-dependent dilation of blood vessels [3,4,5]. They act by improving the circulation and eliciting vascular relaxant properties. TCM herbs contain a large amount of polyphenols, including flavonoids and non-flavonoids, which have cardiovascular protective actions such as eliciting endothelium-dependent vasorelaxation through the increase in release of NO in endothelial cells [7,8]

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