Wogonoside inhibits lipopolysaccharide-induced angiogenesis in vitro and in vivo via toll-like receptor 4 signal transduction.
Wogonoside, one flavonoid derived from the root of Scutellaria baicalensis Georgi, has been reported for its anti-inflammation activity; however, whether it can inhibit inflammation-induced angiogenesis is still unclear. In the present study, we evaluated the effect of wogonoside on lipopolysaccharide (LPS)-induced angiogenesis in vitro and in vivo. Wogonoside suppressed the LPS-stimulated migration and tube formation of human umbilical vein endothelial cells (HUVECs), as well as microvessel sprouting from rat aortic rings in vitro. Moreover, wogonoside also inhibited LPS-stimulated vessel growth of Chicken chorioallantoic membrane (CAM) in vivo. The mechanism revealed that wogonoside inhibited LPS-induced toll-like receptor 4 (TLR4) up-regulation and its downstream mitogen-activated protein kinases (MAPKs) activation, by decreasing the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase. The results suggest that wogonoside inhibits LPS-induced angiogenesis both in vitro and in vivo, and that it might have a therapeutic potential for the diseases associated with the development of both inflammation and angiogenesis progress.
Jiangsu Key Laboratory of Carcinogenesis and Intervention (China Pharmaceutical University), Nanjing 210009, People's Republic of China.
Yan
Y
Chen
Na
N
Lu
Yun
Y
Ling
Ying
Y
Gao
Ling
L
Wang
Yu
Y
Sun
Qi
Q
Qi
Feng
F
Feng
Wenyuan
W
Liu
Wei
W
Liu
Qidong
Q
You
Qinglong
Q
Guo
D000818:Animals; D001011:Aorta / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D049033:Chorioallantoic Membrane; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology*; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000187:drug effects* / Q000378:metabolism; D014471:Umbilical Veins / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism
D044950:Flavanones; D005960:Glucosides; D008070:Lipopolysaccharides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C473995:wogonoside