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

Fang Liang; Yuxiang Han; Hao Gao; Shengchang Xin; Shaodan Chen; Nan Wang; Wei Qin; Hanbing Zhong; Shuo Lin; Xinsheng Yao; Song Li

doi:10.1038/srep14468

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

Sci Rep. 2015 Oct 8:5:14468. doi: 10.1038/srep14468.

Authors

Fang Liang¹, Yuxiang Han¹, Hao Gao², Shengchang Xin¹, Shaodan Chen², Nan Wang¹, Wei Qin¹, Hanbing Zhong³, Shuo Lin^{1

4}, Xinsheng Yao², Song Li¹

Affiliations

¹ Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, Guangdong, 518055, China.
² Institute of Traditional Chinese Medicine &Natural Products, College of Pharmacy, Jinan University, Guangzhou, Guangdong, 510632, China.
³ Department of Biology, South University of Science and Technology of China, Shenzhen, 518055, China.
⁴ Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Angiogenesis Inhibitors / isolation & purification
Angiogenesis Inhibitors / pharmacology*
Animals
Animals, Genetically Modified
Berberidaceae / chemistry*
Biological Assay
Cell Movement / drug effects
Cell Proliferation / drug effects
Chemical Fractionation / methods
Embryo, Nonmammalian
Fibroblast Growth Factors / antagonists & inhibitors
Fibroblast Growth Factors / genetics
Fibroblast Growth Factors / metabolism
Gene Expression Regulation
Human Umbilical Vein Endothelial Cells
Humans
Kaempferols / isolation & purification
Kaempferols / pharmacology*
Medicine, Chinese Traditional
Neovascularization, Physiologic / drug effects*
Plant Extracts / chemistry
Plants, Medicinal
Small Molecule Libraries / isolation & purification
Small Molecule Libraries / pharmacology*
Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors
Vascular Endothelial Growth Factor Receptor-2 / genetics
Vascular Endothelial Growth Factor Receptor-2 / metabolism
Zebrafish
Zebrafish Proteins / antagonists & inhibitors
Zebrafish Proteins / genetics
Zebrafish Proteins / metabolism

Substances

Angiogenesis Inhibitors
Kaempferols
Plant Extracts
Small Molecule Libraries
Zebrafish Proteins
Fibroblast Growth Factors
kaempferol
Vascular Endothelial Growth Factor Receptor-2
kdr protein, zebrafish