Andrographolide, a Novel NF-κB Inhibitor, Inhibits Vascular Smooth Muscle Cell Proliferation and Cerebral Endothelial Cell Inflammation.
BACKGROUND
Aberrant vascular smooth muscle cell (VSMC) proliferation and cerebral endothelial cell (CEC) dysfunction contribute significantly in the pathogenesis of cardiovascular diseases. Therefore, inhibition of these cellular events would be by candidate agents for treating these diseases. In the present study, the mechanism of anti-proliferative and anti-inflammatory effects of andrographolides, a novel nuclear factor-κB inhibitor, was investigated in VSMC and CEC cells.


METHODS
VSMCs and CECs were isolated from rat artery and mouse brain, respectively, and cultured before experimentation. The effect of andro on platelet-derived growth factor-BB (PDGF-BB) induced VSMC cell proliferation was evaluated by cell number, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of extracellular signal regulated kinase 1/2 (ERK1/2), proliferating cell nuclear antigen (PCNA), and the effects on lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) and, cyclooxygenase-2 (COX2) were detected by Western blotting.


RESULTS
Andro significantly inhibited PDGF-BB (10 ng/ml) induced cell proliferation in a concentration (20-100 μM) dependent manner, which may be due to reducing the expression of ERK1/2, and by inhibiting the expression of PCNA. Andro also remarkably diminished LPS-induced iNOS and COX2 expression.


CONCLUSIONS
The results of this study suggested that the effects of andro against VSMCs proliferation and CECs dysfunction may represent a promising approach for treatment of vascular diseases.


BACKGROUND
Andrographolide; CECs; COX2/iNOS; ERK/PCNA; LPS; PDGF-BB; VSMCs.
Department of Cardiology, Cathay General Hospital; ; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University;
Chao-Chien
CC
Chang
Graduate Institute of Engineering Technology, National Taipei University of Technology;
Yeh-Fang
YF
Duann
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University; ; Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Ting-Lin
TL
Yen
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University; ; Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Yu-Ying
YY
Chen
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University; ; Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Thanasekaran
T
Jayakumar
Department of Cardiology, Cathay General Hospital;
Eng-Thiam
ET
Ong
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University; ; Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Joen-Rong
JR
Sheu