{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T11:21:13Z","timestamp":1763810473689,"version":"build-2065373602"},"reference-count":52,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T00:00:00Z","timestamp":1612310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Research Foundation of Korea grant funded by the Korean government","award":["NRF-2020R1I1A3071928 to J.-H.Y. and NRF-2019R1I1A1A01057005 to H.-O.K."],"award-info":[{"award-number":["NRF-2020R1I1A3071928 to J.-H.Y. and NRF-2019R1I1A1A01057005 to H.-O.K."]}]},{"name":"R&amp;D program for Forest Science Technolog provided by Korea Forest Service (Korea Forestry Promotion Institite)","award":["201703B10-1819-BA01 to S.-E.C."],"award-info":[{"award-number":["201703B10-1819-BA01 to S.-E.C."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>As abnormal angiogenesis is associated with exacerbation of various diseases, precise control over angiogenesis is imperative. Vascular endothelial growth factor (VEGF), the most well-known angiogenic factor, binds to VEGF receptor (VEGFR), activates various signaling pathways, and mediates angiogenesis. Therefore, blocking the VEGF-induced angiogenic response-related signaling pathways may alleviate various disease symptoms through inhibition of angiogenesis. Ulmus davidiana is a safe natural product that has been traditionally consumed, but its effects on endothelial cells (ECs) and the underlying mechanism of action are unclear. In the present study, we focused on the effect of a 60% edible ethanolic extract of U. davidiana (U60E) on angiogenesis. U60E inhibited the VEGF-mediated proliferation, tube formation, and migration ability of ECs. Mechanistically, U60E inhibited endothelial nitric oxide synthase activation and nitric oxide production by blocking the protein kinase B signaling pathway activated by VEGF and consequently inhibiting proliferation, tube formation, and migration of ECs. These results suggest that U60E could be a potential and safe therapeutic agent capable of suppressing proangiogenic diseases by inhibiting VEGF-induced angiogenesis.<\/jats:p>","DOI":"10.3390\/molecules26040781","type":"journal-article","created":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T20:31:51Z","timestamp":1612384311000},"page":"781","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A 60% Edible Ethanolic Extract of Ulmus davidiana Inhibits Vascular Endothelial Growth Factor-Induced Angiogenesis"],"prefix":"10.3390","volume":"26","author":[{"given":"Jeongho","family":"Park","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyun-Ouk","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Bioengineering, Kangwon National University, Chuncheon 24341, Korea"},{"name":"Biohealth-Machinery Convergence Engineering, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8816-2976","authenticated-orcid":false,"given":"Kwang-Hyun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Emergency Medical Rescue, Nambu University, Gwangju 62271, Korea"},{"name":"Department of Emergency Medicine, Graduate School of Chonnam National University, Gwangju 61469, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7711-2308","authenticated-orcid":false,"given":"Myung-Bok","family":"Wie","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sun-Eun","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Forest Biomaterials Engineering, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7645-9721","authenticated-orcid":false,"given":"Jang-Hyuk","family":"Yun","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1038\/nature04483","article-title":"Angiogenesis as a therapeutic target","volume":"438","author":"Ferrara","year":"2005","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/S0092-8674(00)80108-7","article-title":"Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis","volume":"86","author":"Hanahan","year":"1996","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1038\/nm.2537","article-title":"Tumor angiogenesis: Molecular pathways and therapeutic targets","volume":"17","author":"Weis","year":"2011","journal-title":"Nat. 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