PUBLICATION

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

Authors
Hu, L., Huang, W., Ding, Y., Liu, M., Wang, M., Wang, Y., Zhang, W., Li, Y., Ye, W., Li, M., Liu, Z.
ID
ZDB-PUB-190426-2
Date
2019
Source
Food & function   10(5): 2605-2617 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Alpinia
  • Vascular Endothelial Growth Factor A/metabolism*
  • Mice, Inbred C57BL
  • Vascular Endothelial Growth Factor Receptor-2/genetics
  • Vascular Endothelial Growth Factor Receptor-2/metabolism*
  • Human Umbilical Vein Endothelial Cells/drug effects
  • Human Umbilical Vein Endothelial Cells/metabolism
  • Cell Movement/drug effects
  • Humans
  • Male
  • Drugs, Chinese Herbal/administration & dosage*
  • Drugs, Chinese Herbal/chemistry
  • Signal Transduction/drug effects
  • Angiogenesis Inhibitors/administration & dosage*
  • Angiogenesis Inhibitors/chemistry
  • Neovascularization, Pathologic/drug therapy*
  • Neovascularization, Pathologic/genetics
  • Neovascularization, Pathologic/metabolism
  • Neovascularization, Pathologic/physiopathology
  • China
  • TOR Serine-Threonine Kinases/genetics
  • TOR Serine-Threonine Kinases/metabolism
  • Female
  • Diarylheptanoids/administration & dosage*
  • Diarylheptanoids/chemistry
  • Animals
  • Zebrafish
PubMed
31020299 Full text @ Food Funct
Abstract
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.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping