title: Kaempferol Identified by Zebrafish Assay and Fine Fractionations Strategy from Dysosma versipellis Inhibits Angiogenesis through VEGF and FGF Pathways.
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.
authors.affiliation: Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, Guangdong, 518055, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liang
authors.affiliation: Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, Guangdong, 518055, China.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Han
authors.affiliation: Institute of Traditional Chinese Medicine &Natural Products, College of Pharmacy, Jinan University, Guangzhou, Guangdong, 510632, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Gao
authors.affiliation: Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, Guangdong, 518055, China.
authors.forename: Shengchang
authors.initials: S
authors.lastname: Xin
authors.affiliation: Institute of Traditional Chinese Medicine &Natural Products, College of Pharmacy, Jinan University, Guangzhou, Guangdong, 510632, China.
authors.forename: Shaodan
authors.initials: S
authors.lastname: Chen
authors.affiliation: Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, Guangdong, 518055, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.affiliation: Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, Guangdong, 518055, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Qin
authors.affiliation: Department of Biology, South University of Science and Technology of China, Shenzhen, 518055, China.
authors.forename: Hanbing
authors.initials: H
authors.lastname: Zhong
authors.affiliation: Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, Guangdong, 518055, China.|Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Shuo
authors.initials: S
authors.lastname: Lin
authors.affiliation: Institute of Traditional Chinese Medicine &Natural Products, College of Pharmacy, Jinan University, Guangzhou, Guangdong, 510632, China.
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Yao
authors.affiliation: Key Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, Guangdong, 518055, China.
authors.forename: Song
authors.initials: S
authors.lastname: Li
mesh_terms: D020533:Angiogenesis Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D030801:Animals, Genetically Modified; D028141:Berberidaceae / Q000737:chemistry*; D001681:Biological Assay; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005591:Chemical Fractionation / Q000379:methods; D004625:Embryo, Nonmammalian; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D044949:Kaempferols / Q000302:isolation & purification / Q000494:pharmacology*; D008516:Medicine, Chinese Traditional; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010936:Plant Extracts / Q000737:chemistry; D010946:Plants, Medicinal; D054852:Small Molecule Libraries / Q000302:isolation & purification / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D044949:Kaempferols; D010936:Plant Extracts; D054852:Small Molecule Libraries; D029961:Zebrafish Proteins; D005346:Fibroblast Growth Factors; C006552:kaempferol; D040301:Vascular Endothelial Growth Factor Receptor-2; C000595917:kdr protein, zebrafish