Abstract

Fo Shou San (FSS) is an ancient herbal decoction comprised of Chuanxiong Rhizoma (CR; Chuanxiong) and Angelicae Sinensis Radix (ASR; Danggui) in a ratio of 2∶3. Previous studies indicate that FSS promotes blood circulation and dissipates blood stasis, thus which is being used widely to treat vascular diseases. Here, we aim to determine the cellular mechanism for the vascular benefit of FSS. The treatment of FSS reversed homocysteine-induced impairment of acetylcholine (ACh)-evoked endothelium-dependent relaxation in aortic rings, isolated from rats. Like radical oxygen species (ROS) scavenger tempol, FSS attenuated homocysteine-stimulated ROS generation in cultured human umbilical vein endothelial cells (HUVECs), and it also stimulated the production of nitric oxide (NO) as measured by fluorescence dye and biochemical assay. In addition, the phosphorylation levels of both Akt kinase and endothelial NO synthases (eNOS) were markedly increased by FSS treatment, which was abolished by an Akt inhibitor triciribine. Likewise, triciribine reversed FSS-induced NO production in HUVECs. Finally, FSS elevated intracellular Ca2+ levels in HUVECs, and the Ca2+ chelator BAPTA-AM inhibited the FSS-stimulated eNOS phosphorylation. The present results show that this ancient herbal decoction benefits endothelial function through increased activity of Akt kinase and eNOS; this effect is causally via a rise of intracellular Ca2+ and a reduction of ROS.

Highlights

  • Fo Shou San (FSS) composed of Angelicae Sinensis Radix [ASR; Danggui; the roots of Angelica sinensis (Oliv) Diels.] and Chuanxiong Rhizoma (CR; Chuanxiong; the rhizomes of Ligusticum chuanxiong Hort.) in a weight ratio of 3:2, is an ancient Chinese herbal decoction

  • In order to demonstrate the ‘‘Promoting Blood Circulation’’ property of FSS, the present study investigated whether FSS protected endothelial function, if so, the underlying mechanisms in relation to nitric oxide (NO) production and radical oxygen species (ROS) reduction in endothelial cells

  • Oxidative stress or increased ROS generation are implicated in hyper-homocysteinemia [18], which is a common and independent risk factor for atherosclerosis and other cardiovascular diseases

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Summary

Introduction

Fo Shou San (FSS) composed of Angelicae Sinensis Radix [ASR; Danggui; the roots of Angelica sinensis (Oliv) Diels.] and Chuanxiong Rhizoma (CR; Chuanxiong; the rhizomes of Ligusticum chuanxiong Hort.) in a weight ratio of 3:2, is an ancient Chinese herbal decoction. According to traditional Chinese medicine (TCM) theory and practice, FSS should be functioned in ‘‘Nourishing Blood’’ and ‘‘Promoting Blood Circulation’’. Our recent reports suggested that FSS was capable of inducing the differentiation of erythropoietic precursor cells and the expression of erythropoietin (EPO), an erythrocyte-specific hematopoietic growth factor, in cultured liver cells [1]. While, another major property of FSS in promoting blood circulation was testified by its ability to inhibit ADP-induced platelet aggregation [2]

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