Chinese herbal remedy wogonin inhibits monocyte chemotactic protein-1 gene expression in human endothelial cells.
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 4x 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.
Chang
Y L
YL
School of Traditional Chinese Medicine, Chang Gung University, Tao-Yuan, Taiwan, Republic of China.
Shen
J J
JJ
Wung
B S
BS
Cheng
J J
JJ
Wang
D L
DL
D000975:Antioxidants / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000975:Antioxidants; D018932:Chemokine CCL2; D004365:Drugs, Chinese Herbal; D044950:Flavanones; D005419:Flavonoids; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate; C085514:wogonin