{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T06:59:03Z","timestamp":1773730743172,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2012,11,12]],"date-time":"2012-11-12T00:00:00Z","timestamp":1352678400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:p><jats:italic>Herba Epimedii<\/jats:italic>, an herb commonly used in East Asian medicine, is commonly used for treatment of impotence, osteoporosis and many inflammatory conditions in traditional Chinese medicine. Recent studies revealed that <jats:italic>Herba Epimedii<\/jats:italic> also has anti\u2010tumor or anti\u2010cancer activities, which may possibly be mediated through anti\u2010angiogenesis. This study aims to examine and confirm the anti\u2010angiogenic activity in the herb using both <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> approaches. The 95% ethanol extract and four subsequent fractions (<jats:italic>n<\/jats:italic>\u2010hexane, ethyl acetate (EA), <jats:italic>n<\/jats:italic>\u2010butanol and aqueous fractions) of <jats:italic>Herba Epimedii<\/jats:italic> were tested on the zebrafish model by the quantitative assay for endogenous alkaline phosphatase; then, the active fraction was further tested on <jats:italic>Tg(fli1a:EGFP)y1<\/jats:italic> zebrafish embryos and human umbilical vein endothelial cells (HUVECs) for the anti\u2010angiogenic effects. In addition, the action mechanism of <jats:italic>Herba Epimedii<\/jats:italic> was further investigated on wild\u2010type zebrafish embryos and HUVECs. The EA fraction showed anti\u2010angiogenic effects in both <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> models. Further experiments demonstrated that it might affect angiogenesis by acting on multiple molecular targets in zebrafish embryos and ERK signaling pathway in HUVECs. In conclusion, <jats:italic>Herba Epimedii<\/jats:italic> can inhibit angiogenesis, which may be the mechanism for its anti\u2010inflammatory, anti\u2010tumor and anti\u2010cancer actions. Copyright \u00a9 2012 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/ptr.4881","type":"journal-article","created":{"date-parts":[[2012,11,13]],"date-time":"2012-11-13T10:58:21Z","timestamp":1352804301000},"page":"1368-1375","source":"Crossref","is-referenced-by-count":25,"title":["Anti\u2010Angiogenic Activity of <i>Herba Epimedii<\/i> on Zebrafish Embryos <i>In Vivo<\/i> and HUVECs <i>In Vitro<\/i>"],"prefix":"10.1002","volume":"27","author":[{"given":"Xiaobin","family":"Yu","sequence":"first","affiliation":[{"name":"School of Chinese Medicine, LKS Faculty of Medicine The University of Hong Kong  10 Sassoon Road Pokfulam Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yao","family":"Tong","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, LKS Faculty of Medicine The University of Hong Kong  10 Sassoon Road Pokfulam Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao\u2010Qiang","family":"Han","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Phytochemistry and Plant Resources in West China, Institute of Chinese Medicine The Chinese University of Hong Kong  Shatin New Territories Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hin\u2010Fai","family":"Kwok","sequence":"additional","affiliation":[{"name":"Institute of Chinese Medicine The Chinese University of Hong Kong  Shatin New Territories Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grace Gar\u2010Lee","family":"Yue","sequence":"additional","affiliation":[{"name":"Institute of Chinese Medicine The Chinese University of Hong Kong  Shatin New Territories Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clara Bik\u2010San","family":"Lau","sequence":"additional","affiliation":[{"name":"Institute of Chinese Medicine The Chinese University of Hong Kong  Shatin New Territories Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Ge","sequence":"additional","affiliation":[{"name":"School of Life Sciences The Chinese University of Hong Kong  Shatin New Territories Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,11,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10147-006-0625-y"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(00)00423-8"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2003.08.086"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-008-9116-8"},{"key":"e_1_2_7_6_1","first-page":"1135","article-title":"Nonflavanoid compounds from Epimedium koreanum","volume":"38","author":"Cheng Y","year":"2007","journal-title":"Chin Tradit Herbal Drugs"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81812-7"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2005.08.002"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-0732"},{"key":"e_1_2_7_10_1","first-page":"5911","article-title":"Hepatocyte growth factor\/scatter factor\u2010induced activation of MEK and PI3K signal pathways contributes to expression of proangiogenic cytokines interleukin\u20108 and vascular endothelial growth factor in head and neck squamous cell carcinoma","volume":"61","author":"Dong G","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_7_11_1","first-page":"385","article-title":"The centennial of the discovery of the antimitotic properties of colchicine","volume":"10","author":"Dustin P","year":"1989","journal-title":"Rev Med Brux"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2403"},{"key":"e_1_2_7_13_1","first-page":"2145","article-title":"Angiopoietin\u20102 is related to tumor angiogenesis in gastric carcinoma: possible in vivo regulation via induction of proteases","volume":"61","author":"Etoh T","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_7_14_1","first-page":"260","article-title":"Angiopoietins, growth factors, and vascular morphology in early arthritis","volume":"30","author":"Fearon U","year":"2003","journal-title":"J Rheumatol"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s001099900019"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0195-27"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2009.09.004"},{"key":"e_1_2_7_18_1","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1097\/SHK.0b013e31815dd92f","article-title":"Circulating angiopoietin 2 correlates with mortality in a surgical population with acute lung injury\/adult respiratory distress syndrome","volume":"29","author":"Gallagher DC","year":"2008","journal-title":"Shock"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.24694"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-5311"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9290(95)00095-X"},{"key":"e_1_2_7_22_1","first-page":"597","article-title":"Receptor tyrosine kinase inhibitors as anti\u2010angiogenic agents","volume":"5","author":"Kim DW","year":"2004","journal-title":"Curr Opin Investig Drugs"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)00008-3"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2001.01316.x"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2002.0711"},{"key":"e_1_2_7_26_1","first-page":"131","article-title":"Icariin\u2010induced apoptosis and related mechanisms in human cancer cells","volume":"6","author":"Li GX","year":"1999","journal-title":"Chin J Cancer Biother"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.3514"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1177\/153303460500400614"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-009-9134-8"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5322.55"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2008.37"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2006.050711"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)00381-6"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81848-6"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2004.09.030"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000251640.77679.D7"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-006-0162-1"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.106.143594"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0b013e318188bd06"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2004.11.017"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-009-9147-3"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-003-0749-6"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.5.1904"},{"key":"e_1_2_7_44_1","first-page":"715","article-title":"Comparison of antioxidative and antitumor activities of six flavonoids from Epimedium koreanum","volume":"33","author":"Wang T","year":"2007","journal-title":"China J Chin Mater Med"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.17.5958-5969.2001"},{"key":"e_1_2_7_46_1","volume-title":"The Zebrafish Book: A Guide for the Laboratory Use of Zebrafish","author":"Westerfield M","year":"1993"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.SLA.0000072111.53797.44"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b12-00130"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.3161"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.3733"},{"key":"e_1_2_7_51_1","first-page":"167","article-title":"Inhibition of Icariin on several tumor cell proliferation by MTT assay","volume":"15","author":"Zhao Y","year":"1995","journal-title":"Shanghai J Immunol"}],"container-title":["Phytotherapy Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fptr.4881","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fptr.4881","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.4881","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,28]],"date-time":"2023-10-28T22:29:50Z","timestamp":1698532190000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ptr.4881"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,11,12]]},"references-count":50,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2013,9]]}},"alternative-id":["10.1002\/ptr.4881"],"URL":"https:\/\/doi.org\/10.1002\/ptr.4881","archive":["Portico"],"relation":{},"ISSN":["0951-418X","1099-1573"],"issn-type":[{"value":"0951-418X","type":"print"},{"value":"1099-1573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,11,12]]}}}