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.
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.
*Department of Pharmacology, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China; †Department of Pathology, College of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China; ‡Department of Immunology, Institute of Clinical Pharmacology,Guangzhou University of Chinese Medicine, Guangzhou,China; and §Department of Pharmacology, Institute for Chinese Medical Research, Sichuan Academy of Chinese Medical Sciences, Chengdu, China.
Haibo
H
Xu
Dejian
D
Wang
Cheng
C
Peng
Xiushen
X
Huang
Ming
M
Ou
Ningsheng
N
Wang
Peixun
P
Wang
Lijuan
L
Zhou
Xiaolin
X
Ye
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D042783:Endothelial Cells / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007962:Leukocytes / Q000187:drug effects*; D009000:Monocytes / Q000187:drug effects; D016328:NF-kappa B / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects; D011817:Rabbits; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1