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Cultivated Orostachys japonicus extract inhibits VEGF-induced angiogenesis via regulation of VEGFR2 signaling pathway in vitro and in vivo.
Cho, Hyun-Dong; Lee, Kwan-Woo; Won, Yeong-Seon; Kim, Jeong-Ho; Seo, Kwon-Il.
Affiliation
  • Cho HD; Industry-Academy Cooperation, Dong-A University, Busan, 49315, Republic of Korea.
  • Lee KW; Department of Biotechnology, Dong-A University, Busan, 49315, Republic of Korea.
  • Won YS; Department of Biotechnology, Dong-A University, Busan, 49315, Republic of Korea.
  • Kim JH; Department of Food Science and Biotechnology, Kyungpook National University, Daegu, 41566, Republic of Korea.
  • Seo KI; Department of Biotechnology, Dong-A University, Busan, 49315, Republic of Korea. Electronic address: kseo@dau.ac.kr.
J Ethnopharmacol ; 256: 112664, 2020 Jun 28.
Article in En | MEDLINE | ID: mdl-32045685
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE Orostachys japonicus A. Berger (O. japonicus), so-called Wa-song in Korea, a traditional food and medicine that grows on mountain rocks and roof tiles. Wa-song containing various phenolic compounds have been reported as a medicinal plant for prevention of fibrosis, cancer, inflammation, and oxidative damage. AIM OF THE STUDY The present study was designed to examine the anti-angiogenic effects of cultivated Orostachys japonicus 70% ethanol extract (CE) in vascular endothelial growth factor (VEGF)-stimulated human umbilical vein endothelial cells (HUVECs). MATERIALS AND

METHODS:

CE was prepared with 70% ethanol. HUVECs, rat aortic rings, and matrigel plug in mice were treated with CE (10-20 µg/mL) and VEGF (20-50 ng/mL), and the anti-angiogenic activities of CE were analyzed by SRB, wound healing, trans-well invasion, capillary-like tubule formation, rat aortas, Western blot, and matrigel plug assay. Phenolic compounds in CE were analyzed using a high-performance liquid chromatography (HPLC)-PDA system.

RESULTS:

Treatment of CE (10-20 µg/mL) markedly suppressed proliferation of HUVECs in the presence (from 136.5% to 112.2%) or absence of VEGF (from 100.0% to 92.1%). The proliferation inhibitory effect of CE was caused by G0/G1 cell cycle arrest, and the decrease of CDK-2, CDK-4, Cyclin D1 and Cyclin E1. Furthermore, CE treatment showed significant angiogenesis inhibitory effects on motility, invasion and micro-vessel formation of HUVECs, rat aortic rings and subcutaneous matrigels under VEGF-stimulation condition. In HUVECs, CE-induced anti-angiogenic effect was regulated by inhibition of the PI3K/AKT/mTOR, MAPK/p38, MAPK/ERK, FAK-Src, and VEGF-VEGFR2 signaling pathways.

CONCLUSION:

This study demonstrated that CE might be used as a potential natural substance, multi-targeted angiogenesis inhibitor, functional food material.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Plant Extracts / Signal Transduction / Angiogenesis Inhibitors / Crassulaceae / Vascular Endothelial Growth Factor Receptor-2 / Vascular Endothelial Growth Factor A / Neovascularization, Pathologic Limits: Animals / Humans / Male Language: En Journal: J Ethnopharmacol Year: 2020 Document type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Plant Extracts / Signal Transduction / Angiogenesis Inhibitors / Crassulaceae / Vascular Endothelial Growth Factor Receptor-2 / Vascular Endothelial Growth Factor A / Neovascularization, Pathologic Limits: Animals / Humans / Male Language: En Journal: J Ethnopharmacol Year: 2020 Document type: Article