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.
Chen
Yan
Y
Jiangsu Key Laboratory of Carcinogenesis and Intervention (China Pharmaceutical University), Nanjing 210009, People's Republic of China.
Lu
Na
N
Ling
Yun
Y
Gao
Ying
Y
Wang
Ling
L
Sun
Yu
Y
Qi
Qi
Q
Feng
Feng
F
Liu
Wenyuan
W
Liu
Wei
W
You
Qidong
Q
Guo
Qinglong
Q
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