Chinese Herbal Remedy Wogonin Inhibits Monocyte
Chemotactic Protein-1 Gene Expression in Human Endothelial
Cells
YING-LING CHANG, JIANN-JONG SHEN, BEING-SUN WUNG, JING-JY CHENG, and DANNY LING WANG
School of Traditional Chinese Medicine, Chang Gung University, Tao-Yuan, Taiwan, Republic of China (Y.-L.C., J.-J.S.); and Institute of
Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China (B.-S.W., .J.-J.C., D.L.W.)
Received January 4, 2001; accepted May 23, 2001
This paper is available online at http://molpharm.aspetjournals.org
ABSTRACT
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 investi-
gated 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-depen-
dent 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 activ-
ity 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 conc