Department of Emergency Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei City, Taiwan.
J Agric Food Chem. 2010 Jun 9;58(11):7082-7. doi: 10.1021/jf100421w.
Chrysin, 5,7-dihydroxyflavone, possesses many biologic properties. This study aimed to investigate the effects and molecular mechanisms of chrysin on IL-6-induced angiogenesis in vitro and in ovo. Chicken chorioallantoic membrane assay, an in ovo angiogenesis assay, showed chrysin significantly suppressed IL-6-induced neovascularization. Furthermore, chrysin significantly suppressed human umbilical vein endothelial cell (HUVECs) migration and tube formation. The signaling pathway involved in chrysin-related antiangiogenesis was also investigated. The data indicated that chrysin is able to down-regulate the expression of glycoprotein 130 (gp130), soluble IL-6 receptor (IL-6R), phosphorylated JAK1 and STAT3, and VEGF in HUVECs. The IL-6-induced binding of STAT3 was significantly suppressed by chrysin. Moreover, chrysin did not further suppress VEGF expression with STAT3 knocked down. Taken together, the results show that chrysin suppresses IL-6-induced angiogenesis through modulation of the sIL-6R/gp130/JAK1/STAT3/VEGF signaling pathway. Chrysin may provide new therapeutic potential for IL-6-induced pathological angiogenesis.
白杨素，5,7-二羟基黄酮，具有许多生物学特性。本研究旨在探讨白杨素对体外和鸡胚中 IL-6 诱导的血管生成的作用及其分子机制。鸡胚绒毛尿囊膜试验是一种鸡胚血管生成试验，结果表明白杨素能显著抑制 IL-6 诱导的新生血管形成。此外，白杨素还能显著抑制人脐静脉内皮细胞（HUVEC）的迁移和管腔形成。还研究了与白杨素相关的抗血管生成的信号通路。研究数据表明，白杨素能够下调 HUVEC 中糖蛋白 130（gp130）、可溶性白细胞介素 6 受体（IL-6R）、磷酸化 JAK1 和 STAT3 以及 VEGF 的表达。白杨素显著抑制了 IL-6 诱导的 STAT3 结合。此外，用 STAT3 敲低后，白杨素对 VEGF 的表达没有进一步抑制作用。综上所述，研究结果表明，白杨素通过调节 sIL-6R/gp130/JAK1/STAT3/VEGF 信号通路抑制 IL-6 诱导的血管生成。白杨素可能为 IL-6 诱导的病理性血管生成提供新的治疗潜力。
