Angelica sinensis has inherent endothelial cell toxicity at high concentrations but can also protect the vascular endothelium from oxidative stress-induced injury at moderate concentrations

Abstract

Hypoxia and oxidative stress are important factors in the pathogenesis of many acute forms of injury, especially acute kidney injury. Apoptosis is a key mode of endothelial cell death from oxidative stress. Minimising the detrimental effects of oxidative stress is necessary to reduce injury, and new treatment strategies are constantly being sought. The aim of this study was to investigate the ability of an aqueous/methanol extract of Angelica sinensis (AS) root (Chinese names Danggui, Dong quai, Donggui) to protect endothelium from hypoxia and oxidative stress. This was compared in specialised kidney endothelium (renal medullary vascular endothelial cells; RMVEC) versus central endothelium (aortic endothelial cells; AEC). Toxicity of various strengths of AS was first tested in RMVEC and AEC using % apoptosis and mitosis as outcomes. Morphological and molecular characteristics of apoptosis and mitosis, and the effect of AS on heme-oxygenase-1, a marker of cellular response to oxidative stress, were also investigated. The results showed that, at concentrations of 2500µg/mL or greater, AS significantly increased apoptosis in RMVEC and AEC (P<0.05), however concentrations of 2000 µg/mL or less were non-toxic and also non-mitogenic. Endothelial cells were then treated with hydrogen peroxide (0.8 mM for RMVEC; 0.6 mM for AEC) for oxidative stress, with and without 2000 µg/mL AS. AS significantly inhibited oxidant-induced apoptosis (P<0.05) but had little effect on mitosis. AS also increased heme-oxygenase-1, but only in AEC. AS extracts may have some inherent toxicity at high concentrations, but with careful analysis of non-toxic levels, both renal and central endothelium benefited from AS against oxidative stress-induced apoptosis, without inducing excessive mitosis, and AS may find application in some oxidant-induced disease.