Rabbit Sera Containing Compound Danshen Dripping Pill Attenuate Leukocytes Adhesion to TNF-Alpha–Activated Human Umbilical Vein Endothelial Cells by Suppressing Endothelial ICAM-1 and VCAM-1 Expression Through NF-KappaB Signaling Pathway

Abstract

The adherence to circulating leukocytes, such as monocytes and neutrophils, to vascular endothelial cells is of central importance to the pathogenesis of various cardiovascular diseases (CVDs) including atherosclerosis and myocardial ischemia-reperfusion injury. Compound danshen dripping pill (CDDP; Fufang Danshen Diwan in Chinese), namely cardiotonic pill, is extensively used for CVDs medication in China and some other countries. Here, we sought to investigate the effect of CDDP on leukocytes binding to vascular endothelial cells and elaborate the possibly underlying mechanism. Using seropharmacological method, rabbit sera containing CDDP were shown to mitigate the adhesiveness of monocytes and neutrophils to tumor necrosis factor alpha-stimulated human umbilical vein endothelial cells in dose and time-dependent manners, alleviate the levels of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 messenger RNA and protein dose dependently and also encumber IκBα degradation, p65 nuclear translocation, nuclear factor-kappaB (NF-κB) DNA-binding activity, and NF-κB-responsive gene transcription in tumor necrosis factor alpha-activated human umbilical vein endothelial cells. This study suggests that CDDP protects against CVDs potentially by attenuation of leukocytes-endothelium adhesion cascade via lessening endothelial cell adhesion molecules expression and NF-κB signaling pathway activity.