β-Amyrin induces angiogenesis in vascular endothelial cells through the Akt/endothelial nitric oxide synthase signaling pathway.
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.
Department of Oral and Maxillofacial Prosthodontics, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima 890-8544, Japan. Electronic address: masai@dent.kagoshima-u.ac.jp.
Masakazu
M
Ishii
Maruzen Pharmaceuticals Co., Ltd., Hiroshima 729-3102, Japan.
Tatsuo
T
Nakahara
Maruzen Pharmaceuticals Co., Ltd., Hiroshima 729-3102, Japan.
Shingo
S
Ikeuchi
Department of Oral and Maxillofacial Prosthodontics, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima 890-8544, Japan.
Masahiro
M
Nishimura
D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009569:Nitric Oxide / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
D009569:Nitric Oxide; D009828:Oleanolic Acid; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; C036380:beta-amyrin
Angiogenesis; Endothelial cell; NO; eNOS; β-Amyrin