Kaempferol, a Major Flavonoid in Ginkgo Folium, Potentiates Angiogenic Functions in Cultured Endothelial Cells by Binding to Vascular Endothelial Growth Factor

Wei-Hui Hu; Huai-You Wang; Yi-Teng Xia; Diana Kun Dai; Qing-Ping Xiong; Tina Ting-Xia Dong; Ran Duan; Gallant Kar-Lun Chan; Qi-Wei Qin; Karl Wah-Keung Tsim

doi:10.3389/fphar.2020.00526

Kaempferol, a Major Flavonoid in Ginkgo Folium, Potentiates Angiogenic Functions in Cultured Endothelial Cells by Binding to Vascular Endothelial Growth Factor

Front Pharmacol. 2020 Apr 28:11:526. doi: 10.3389/fphar.2020.00526. eCollection 2020.

Authors

Wei-Hui Hu^{1

2

3}, Huai-You Wang^{1

2}, Yi-Teng Xia^{1

2}, Diana Kun Dai^{1

2}, Qing-Ping Xiong^{2

4}, Tina Ting-Xia Dong^{1

2}, Ran Duan^{1

2}, Gallant Kar-Lun Chan^{1

2}, Qi-Wei Qin³, Karl Wah-Keung Tsim^{1

2}

Affiliations

¹ Shenzhen Key Laboratory of Edible and Medicinal Bioresources, The Hong Kong University of Science and Technology, Nanshan, Shenzhen, China.
² Division of Life Science and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, Hong Kong.
³ Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou, China.
⁴ Jiangsu Key Laboratory of Regional Resource Exploitation and Medicinal Research, Huaiyin Institute of Technology, Jiangsu, China.

Abstract

Kaempferol is a major flavonoid in Ginkgo Folium and other edible plants, which is being proposed here to have roles in angiogenesis. Angiogenesis is important in both physiological and pathological development. Here, kaempferol was shown to bind with vascular endothelial growth factor (VEGF), probably in the heparin binding domain of VEGF: this binding potentiated the angiogenic functions of VEGF in various culture models. Kaempferol potentiated the VEGF-induced cell motility in human umbilical vein endothelial cells (HUVECs), as well as the sub-intestinal vessel sprouting in zebrafish embryos and formation of microvascular in rat aortic ring. In cultured HUVECs, application of kaempferol strongly potentiated the VEGF-induced phosphorylations of VEGFR2, endothelial nitric oxide synthase (eNOS) and extracellular signal-regulated kinase (Erk) in time-dependent and concentration-dependent manners, and in parallel the VEGF-mediated expressions of matrix metalloproteinases (MMPs), MMP-2 and MMP-9, were significantly enhanced. In addition, the potentiation effect of kaempferol was revealed in VEGF-induced migration of skin cell and monocyte. Taken together, our results suggested the pharmacological roles of kaempferol in potentiating VEGF-mediated functions should be considered.

Keywords: Ginkgo biloba; VEGF; angiogenesis; herbal medicine; kaempferol.