RT Journal Article
SR Electronic
T1 Chinese Herbal Remedy Wogonin Inhibits Monocyte Chemotactic Protein-1 Gene Expression in Human Endothelial Cells
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 507
OP 513
VO 60
IS 3
A1 Chang, Ying-Ling
A1 Shen, Jiann-Jong
A1 Wung, Being-Sun
A1 Cheng, Jing-Jy
A1 Wang, Danny Ling
YR 2001
UL http://molpharm.aspetjournals.org/content/60/3/507.abstract
AB Wogonin (Wog), an active component of Scutellaria baicalensis, has antioxidant and anti-inflammatory properties. Monocyte chemotactic protein-1 (MCP-1), a potent chemoattractant for monocytes, plays a crucial role in case of early inflammatory responses, including atherosclerosis. In this study, we investigated the effect of Wog on phorbol ester (PMA)-induced MCP-1 expression in human umbilical vein endothelial cells (ECs). The MCP-1 mRNA levels and MCP-1 release in Wog-treated ECs were measured. Wog inhibited PMA-induced MCP-1 mRNA levels and MCP-1 secretion in a dose-dependent manner. The inhibition of MCP-1 induction by Wog is a transcriptional event, as shown by Wog's significant reduction of both MCP-1 promoter and 4× 12-O-tetradecanoylphorbol-13-acetate response element-luciferase reporter activities. By electrophoretic mobility assay, Wog significantly reduced the AP-1 binding activity induced by PMA. Furthermore, the PMA-induced extracellular signal-regulated kinase 1/2 and c-Jun amino-terminal kinase activities that contributed to AP-1 activity and MCP-1 gene induction were obviously attenuated after pretreating ECs with Wog. The decrease of MCP-1 secretion by Wog pretreatment led to a reduction of monocyte adhesion to ECs. Taken together, our results demonstrate that Wog inhibits MCP-1 induction in ECs; this inhibition is mediated by reducing AP-1 transcriptional activity via the attenuation of ERK1/2 and JNK signal transduction pathways. We conclude that Wog has the potential therapeutic development for use in anti-inflammatory and vascular disorders. The American Society for Pharmacology and Experimental Therapeutics