Kaempferol Identified by Zebrafish Assay and Fine Fractionations Strategy from Dysosma versipellis Inhibits Angiogenesis through VEGF and FGF Pathways.
Kaempferol Identified by Zebrafish Assay and Fine Fractionations Strategy from Dysosma versipellis Inhibits Angiogenesis through VEGF and FGF Pathways.
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DOI：
10.1038/srep14468
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发表时间：
2015-10-08
影响因子：
4.6
通讯作者：
Li S
中科院分区：
文献类型：
--
作者：
Liang F;Han Y;Gao H;Xin S;Chen S;Wang N;Qin W;Zhong H;Lin S;Yao X;Li S
天然产物是发现治疗物质的丰富资源。直接利用504个中药提取物的有效部位，进行了基于转基因斑马鱼的抗血管生成活性物质筛选。发现一种组分DYVE-D3抑制斑马鱼脉管系统中节间血管的生长。生物活性导向分离表明，DYVE-D3的活性物质为黄酮类山奈酚。山奈酚还能抑制HUVECs的增殖和迁移。此外，我们发现山奈酚通过抑制VEGFR 2表达来抑制血管生成，而FGF抑制可以增强VEGFR 2表达。总之，本研究表明，构建精细级分文库可以有效地鉴定天然产物中的活性物质。
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.