Protective role of wogonin against lipopolysaccharide-induced angiogenesis via VEGFR-2, not VEGFR-1.
Wogonin, one of flavonoid derived from particular plants, enriches the property of anti-inflammation. Inflammation-stimulated angiogenesis plays an important role in many pathological diseases, such as rheumatoid arthritis, atherosclerosis, and cancer. The aim of this study was to investigate the suppressive effect of wogonin on lipopolysaccharide (LPS)-induced angiogenesis in human umbilical endothelial cell (HUVEC) cultures. By cell differentiation assays, migration and tube formation activity under LPS treatment were evaluated. Besides, IL-6 neutralizing antibody was added to test the inhibitory effect in the phenotypic alteration. Western blot analysis, ELISA cytokine assay, and quantitative real time-PCR were performed for VEGF, IL-6, VEGF receptors, and IL-6 receptor gene expressions on HUVEC with wogonin treatment. Furthermore, in vivo chorioallantoic membrane (CAM) assay was applied to evaluate the percentage of new vessels formation. The results revealed that wogonin (10(-8)-10(-5) M) inhibited LPS-induced angiogenesis in a concentration-dependent manner. The mRNA and protein expressions of VEGF, VEGFR-2, IL-6, and sIL-6Ralpha were attenuated (P<0.05), but not VEGFR-1. In the LPS-induced CAM model, our data suggested that wogonin (10(-8)-10(-5) M) significantly decreased new vessel formation and vascular network (P<0.05). We conclude that wogonin suppresses both in vitro and in vivo LPS-induced angiogenesis, through VEGFR-2, but not VEGFR-1.
Lin
Chiu-Mei
CM
Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
Chang
Hang
H
Chen
Yeh-Hsu
YH
Li
Shih Yun
SY
Wu
I-Hsing
IH
Chiu
Jen-Hwey
JH
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002642:Chick Embryo; D042783:Endothelial Cells / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects; D044950:Flavanones / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000188:drug therapy*; D012333:RNA, Messenger / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism*
D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D044950:Flavanones; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; C085514:wogonin