Down‐Regulation of CD40 Gene Expression and Inhibition of Apoptosis with Danshensu in Endothelial Cells

Abstract

Danshen is commonly used in China for the treatment of atherosclerosis-related disorders such as cardiovascular and cerebrovascular diseases. Research shows that it also has immunostimulation properties. The present study evaluates the protective effect of danshensu, an active water-extractable component isolated from danshen, on an endothelial cell line (CRL-1730) treated with hydrogen peroxide (H 2 O 2 ). Danshensu significantly inhibited endothelial cell viability induced by H 2 O 2 . The treatment of endothelial cells with danshensu resulted in most cells being arrested in the S and G 2 /M phases of the cell cycle. The fraction of cells in G 0 /G 1 phase was markedly decreased by danshensu treatment compared to the control groups. The apoptosis was also markedly decreased after danshensu treatment. Additionally, danshensu restrains decreased nitric oxide level, increased the release of lactate dehydrogenase and expression of cluster of differentiation 40 (CD40) significantly. These results suggest that danshensu protects endothelial cells from the damage induced by H 2 O 2 through its CD40 anti-inflammatory approach and cell apoptosis inhibition.Danshen, a traditional Chinese herbal medicine, is the dried roots of the plant Salvia miltiorrhiza Bunge belonging to the Labiata family. It has often been used in the prevention of cardiovascular and cerebrovascular diseases such as atherosclerosis, myocardial infarction [1]. It is known that danshen contains hydrophilic phenolics (salvianolic acid B and danshensu) and lipophilic quinines (tanshinone I, tanshinone IIA) and displays various pharmacological properties [2]. The effect of danshen on cardiovascular diseases is partially attributed to the anti-atherosclerosis property of danshensu.In vitro experiments indicate that tanshinone IIA can decrease the expression of intercellular adhesion molecular-1 in human umbilical vein endothelial cells (HUVEC) induced by tumour necrosis factor-α (TNF-α ) and inhibit the oxidation of low-density lipoprotein [3,4]. Moreover, our studies show that tanchinone IIA has a protective effect against apoptosis of endothelial cells injured by H 2 O 2 via decrease of the content of malondialdehyde [5]. However, since the water decoction is the commonly used preparation/method in preparing Chinese folk medicine for human consumption, current research is focused on the water-soluble compounds. Danshensu has received much attention as it is an abundant active constituent. The cell membrane stationary phase from the transient over the expression of cluster of differentiation (CD40) in HUVEC was prepared and used to screen the effective anti-atherosclerotic components of danshen extracts. Based on the cell membrane stationary phase experiments, it has been clearly shown that tanshinone IIA and danshensu have much higher activity than other components from danshen extracts [6]. Previous studies have established that the tanshinone IIA protective effect against atherosclerosis is mediated by decreasing the expression of CD40 in v...

Tanshinone II A Attenuates TNF-α-Induced Expression of VCAM-1 and ICAM-1 in Endothelial Progenitor Cells by Blocking Activation of NF-κB

“…Inflammation is involved in all stages of the atherosclerosis, including lesion formation and plaque stability [22]. The adhesion of inflammatory cells to the vascular endothelium plays important role in atherogenic processes [23].…”

Cardioprotective effect of Danshensu against myocardial ischemia/reperfusion injury and inhibits apoptosis of H9c2 cardiomyocytes via Akt and ERK1/2 phosphorylation

“…1. Several experiments have demonstrated biological activities of Danshensu in improving microcirculation, suppressing the formation of reactive oxygen species, inhibiting platelet adhesion and aggregation, protecting myocardium against ischemia, protecting endothelial cells against injury induced by inflammation (Cheng, 2007;Wang et al, 2009;Han et al, 2009;Chan et al, 2004;Yang et al, 2009).…”

Renal Tubular Secretion of Tanshinol: Molecular Mechanisms, Impact on Its Systemic Exposure, and Propensity for Dose-Related Nephrotoxicity and for Renal Herb-Drug Interactions

“…Studies have shown that tanshinol exhibited vasodilatory properties, elevated serum nitric oxide levels and action of endothelial nitric oxide synthase, protected endothelial cells from homocysteine-induced injury and H 2 O 2 -induced apoptosis, and exerted antioxidant effects (Chan et al, 2004;Lam et al, 2007;Zhao et al, 2008;Yang et al, 2009;. Tanshinol also decreased blood pressure in spontaneously hypertensive rats and attenuated cardiac hypertrophy, venular thrombosis, and methionine-induced hyperhomocysteinemia in rats (Cao et al, 2009;Wang et al, 2009;Yang et al, 2010;Tang et al, 2011a,b).…”