Kaempferol Identified by Zebrafish Assay and Fine Fractionations Strategy from Dysosma versipellis Inhibits Angiogenesis through VEGF and FGF Pathways

被引:0
作者
Fang Liang
Yuxiang Han
Hao Gao
Shengchang Xin
Shaodan Chen
Nan Wang
Wei Qin
Hanbing Zhong
Shuo Lin
Xinsheng Yao
Song Li
机构
[1] Key Laboratory of Chemical Genomics,Department of Biology
[2] School of Chemical Biology and Biotechnology,Department of Molecular
[3] Peking University Shenzhen Graduate School,undefined
[4] Institute of Traditional Chinese Medicine & Natural Products,undefined
[5] College of Pharmacy,undefined
[6] Jinan University,undefined
[7] South University of Science and Technology of China,undefined
[8] Cell and Developmental Biology,undefined
[9] University of California,undefined
[10] Los Angeles,undefined
来源
Scientific Reports | / 5卷
关键词
D O I
暂无
中图分类号
学科分类号
摘要
Natural products are a rich resource for the discovery of therapeutic substances. By directly using 504 fine fractions from isolated traditional Chinese medicine plants, we performed a transgenic zebrafish based screen for anti-angiogenesis substances. One fraction, DYVE-D3, was found to inhibit the growth of intersegmental vessels in the zebrafish vasculature. Bioassay-guided isolation of DYVE-D3 indicates that the flavonoid kaempferol was the active substance. Kaempferol also inhibited the proliferation and migration of HUVECs in vitro. Furthermore, we found that kaempferol suppressed angiogenesis through inhibiting VEGFR2 expression, which can be enhanced by FGF inhibition. In summary, this study shows that the construction of fine fraction libraries allows efficient identification of active substances from natural products.
引用
收藏
相关论文
共 92 条
  • [1] Koehn FE(2005)The evolving role of natural products in drug discovery Nat Rev Drug Discov 4 206-20
  • [2] Carter GT(2012)Natural Products As Sources of New Drugs over the 30 Years from 1981 to 2010 Journal of Natural Products 75 311-335
  • [3] Newman DJ(2009)Impact of Natural Products on Developing New Anti-Cancer Agents Chemical Reviews 109 3012-3043
  • [4] Cragg GM(2005) drug discovery in the zebrafish Nat Rev Drug Discov 4 35-44
  • [5] Cragg GM(2011)Zebrafish bioassay-guided natural product discovery: isolation of angiogenesis inhibitors from East african medicinal plants PLoS One 6 e14694-601
  • [6] Grothaus PG(2011)Dehydro-alpha-lapachone, a plant product with antivascular activity Proc Natl Acad Sci USA 108 11596-301
  • [7] Newman DJ(2001)The vascular anatomy of the developing zebrafish: an atlas of embryonic and early larval development Dev Biol 230 278-82
  • [8] Zon LI(2002)Patterning of angiogenesis in the zebrafish embryo Development 129 973-2
  • [9] Peterson RT(2003)Rapid analysis of angiogenesis drugs in a live fluorescent zebrafish assay Arterioscler Thromb Vasc Biol 23 911-692
  • [10] Crawford AD(2006)Drug Insight: vascular disrupting agents and angiogenesis—novel approaches for drug delivery Nature Clinical Practice Oncology 3 682-11392