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PHMH, a diarylheptanoid from Alpinia officinarum attenuates VEGF-induced angiogenesis via inhibition of the VEGFR-2 signaling pathway

HuThese authors contributed equally to this paper., Liubing, Huang, Weihuan, Ding, Yong, Liu, Min, Wang, Mei, Wang, Ying, Zhang, Wei, Li, Yaolan, Ye, Wencai, Li, Manmei, Liu, Zhong
Food & function 2019 v.10 no.5 pp. 2605-2617
Alpinia officinarum, Danio rerio, angiogenesis, antioxidant activity, aorta, chorioallantoic membrane, condiments, human umbilical vein endothelial cells, mice, models, rats, rhizomes, signal transduction, spices, therapeutics, vascular endothelial growth factor receptor-2, vascular endothelial growth factors, viability, China, Europe
The rhizome of Alpinia officinarum Hance, a popular spice used as a condiment in China and Europe, has various reported bioactivities, including anticancer, anti-inflammatory and antioxidant effects. However, its anti-angiogenic activity has not previously been reported. In this study, a diarylheptanoid was isolated from Alpinia officinarum and identified as 1-phenyl-7-(4-hydroxy-3-methoxyphenyl)-4E-en-3-heptanone (PHMH). We demonstrated that PHMH exerts anti-angiogenic activity both in vitro and in vivo. PHMH inhibited vascular endothelial growth factor (VEGF)-induced viability, migration, invasion and tube formation in human umbilical vein endothelial cells (HUVECs) in vitro, and also suppressed VEGF-induced sprout formation of rat aorta ex vivo. Furthermore, PHMH was found to block VEGF-induced vessel formation in mice and suppress angiogenesis in both zebrafish and chorioallantoic membrane models. Mechanistic studies indicated that PHMH inhibited VEGF-induced VEGF receptor-2 (VEGFR-2) auto-phosphorylation and resulted in the blockage of VEGFR-2-mediated signaling cascades in HUVECs, including the Akt/mTOR, ERK1/2, and FAK pathways. Our findings provide new insights into the potential application of PHMH as a therapeutic agent for anti-angiogenesis.