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β-Amyrin induces angiogenesis in vascular endothelial cells through the Akt/endothelial nitric oxide synthase signaling pathway.

Abstract
β-Amyrin is a pentacyclic triterpene found in various plants and has a variety of biological and pharmacological activities. However, the angiogenic effects of β-amyrin in vascular endothelial cells have not been elucidated. Herein, we investigated the effects of β-amyrin on angiogenesis and evaluated the underlying molecular mechanisms. β-Amyrin treatment had no cytotoxic effect on cultured human umbilical vein endothelial cells (HUVECs). It promoted the formation of tube-like structures and enhanced HUVEC migration and the phosphorylation of Akt and endothelial nitric oxide synthase (eNOS) in HUVECs. Pre-treatment with a PI3 kinase or NOS inhibitor blocked β-amyrin-induced phosphorylation of Akt and eNOS. β-Amyrin treatment significantly induced nitric oxide (NO) production in HUVECs. Furthermore, pre-treatment with a PI3 kinase or NOS inhibitor significantly inhibited β-amyrin-induced tube-like structures formation of vascular endothelial cells and HUVEC migration. These data indicate that β-amyrin-induced angiogenesis in vascular endothelial cells may be mediated by Akt-eNOS signaling-dependent mechanisms. These findings suggest that β-amyrin could be a novel therapeutic agent for ischemic vascular diseases.
AuthorsMasakazu Ishii, Tatsuo Nakahara, Shingo Ikeuchi, Masahiro Nishimura
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 467 Issue 4 Pg. 676-82 (Nov 27 2015) ISSN: 1090-2104 [Electronic] United States
PMID26498523 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier Inc. All rights reserved.
Chemical References
  • Nitric Oxide
  • Oleanolic Acid
  • Nitric Oxide Synthase Type III
  • Proto-Oncogene Proteins c-akt
  • beta-amyrin
Topics
  • Endothelium, Vascular (drug effects, enzymology, physiology)
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Neovascularization, Physiologic (drug effects)
  • Nitric Oxide (biosynthesis)
  • Nitric Oxide Synthase Type III (metabolism)
  • Oleanolic Acid (analogs & derivatives, pharmacology)
  • Proto-Oncogene Proteins c-akt (metabolism)
  • Signal Transduction (drug effects)

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