Chunghyuldan activates NOS mRNA expression and suppresses VCAM-1 mRNA expression in human endothelial cells.
Chunghyuldan (CHD), a combinatorial drug that has antihyperlipidemic and anti-inflammatory activities, has been shown to improve arterial stiffness and inhibit stroke recurrence in clinical study. To understand the molecular basis of CHD's clinical effects, we explored its effect on cell proliferation and expression of nitric oxide synthase (NOS) and vascular cell adhesion molecule (VCAM-1) in human umbilical vein endothelial cells (HUVECs). Cell number counting and [3H]thymidine incorporation assay demonstrated that nontoxic doses of CHD have an inhibitory effect on DNA synthesis and suppress cell cycle progression of HUVECs. CHD treatment led to a marked induction of NO production through up-regulation of NOS mRNA expression in a dose- and time-dependent manner, whereas it suppressed VCAM-1 expression. CHD inhibition of VCAM-1 expression was totally blocked by pretreatment with the NO synthesis inhibitor L-NMMA, whereas pretreatment with the NO donor DETA-NO further decreased VCAM-1 level in CHD-treated HUVECs, indicating that VCAM-1 regulation by CHD is mediated through increased NO synthesis by CHD. In addition, TNF-alpha-mediated VCAM-1 activation was substantially impeded by CHD treatment. Collectively, our data suggest that anti-inflammatory or anti-hyperlipidemic effects of CHD might be associated with its ability to activate NO production and suppress VCAM-1 expression in human endothelial cells.
Park
Seong-Uk
SU
Department of Cardiovascular and Neurologic Diseases (Stroke Center), Kyung-Hee Oriental Medical Center, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-702, Korea.
Jung
Woo-Sang
WS
Moon
Sang-Kwan
SK
Ko
Chang-Nam
CN
Cho
Ki-Ho
KH
Kim
Young-Suk
YS
Bae
Hyung-Sup
HS
Chi
Sung-Gil
SG
D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D009573:Nitrites / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles; D013936:Thymidine / Q000378:metabolism; D014226:Triazenes / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*; D019323:omega-N-Methylarginine / Q000494:pharmacology
C105351:1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene; C499382:Chunghyuldan; D018076:DNA, Complementary; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D009573:Nitrites; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; D014226:Triazenes; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C022616:thiazolyl blue; D013936:Thymidine