{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:45:56Z","timestamp":1787013956690,"version":"build-2736575974"},"reference-count":63,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2015,6,26]],"date-time":"2015-06-26T00:00:00Z","timestamp":1435276800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Future-Based Technology Development program through the National Research Foundation (NRF) of Korea funded by the Ministry of Education, Science, and Technology","award":["2012-0006131"],"award-info":[{"award-number":["2012-0006131"]}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2015,8]]},"abstract":"\n Background and Purpose<\/jats:title>\n Abnormally induced angiogenesis and lymphangiogenesis are associated with human diseases, including neovascular eye disease. Substances that inhibit these processes may have potential as an attractive therapeutic strategy for these diseases.<\/jats:p>\n <\/jats:sec>\n \n Experimental Approach<\/jats:title>\n \n In vitro<\/jats:italic>\n and\n in vivo<\/jats:italic>\n angiogenesis and\/or lymphangiogenesis were assessed in\n VEGF<\/jats:styled-content>\n \u2010 or hypoxia\u2010stimulated endothelial and retinal cells and in animal models of oxygen\u2010induced retinopathy (\n OIR<\/jats:styled-content>\n ), streptozotocin\u2010induced diabetic retinopathy (\n SIDR<\/jats:styled-content>\n ), suture\u2010induced inflammatory corneal neovascularization (\n SICNV<\/jats:styled-content>\n ) and silver nitrate\u2010induced corneal neovascularization.\n HUVECs<\/jats:styled-content>\n and retinal cells were cultured under hypoxic conditions or incubated with\n VEGF<\/jats:styled-content>\n to identify the molecular mechanisms involved.\n <\/jats:p>\n <\/jats:sec>\n \n Key Results<\/jats:title>\n \n The imidazole\u2010based alkaloid derivative\n LCB<\/jats:styled-content>\n 54\u20100009 inhibited capillary\u2010like tube formation in\n VEGF<\/jats:styled-content>\n \u2010induced\n HUVECs<\/jats:styled-content>\n without inducing cytotoxic effects. Intravitreal injection of\n LCB<\/jats:styled-content>\n 54\u20100009 into retinas suppressed the formation of the pathological neovascular tufts and increased vascular permeability in both\n OIR<\/jats:styled-content>\n of mice and\n SIDR<\/jats:styled-content>\n of rats. Furthermore, subconjunctival injection of\n LCB<\/jats:styled-content>\n 54\u20100009 into the cornea suppressed corneal inflammation and inflammation\u2010associated angiogenesis and lymphangiogenesis in\n SICNV<\/jats:styled-content>\n of mice and silver nitrate cauterization of rats. These pharmacological activities were associated with effects on\n HIF<\/jats:styled-content>\n \u20101\u03b1 protein stability and\n HIF<\/jats:styled-content>\n \u20101\u03b1\/\n NF<\/jats:styled-content>\n \u2010\n \u03baB<\/jats:styled-content>\n redox sensitivity through its antioxidant activities.\n LCB<\/jats:styled-content>\n 54\u20100009 also inhibited the hypoxia\u2010induced expression of angiopoietin\u20102, and\n VEGF<\/jats:styled-content>\n \u2010induced\n VEGFR<\/jats:styled-content>\n \u20102 activation and downstream signalling, resulting in the down\u2010regulation of the expression of pro\u2010angiogenic factors and pro\u2010inflammatory mediators and an up\u2010regulation of the expression of anti\u2010angiogenic factors.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Implications<\/jats:title>\n \n LCB<\/jats:styled-content>\n 54\u20100009 is a potential candidate molecule for blocking pathological angiogenesis and lymphangiogenesis mediated by\n HIF<\/jats:styled-content>\n \u20101\u03b1\u2010 angiopoietin\u20102 expression and\n VEGFR<\/jats:styled-content>\n \u20102 activation.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bph.13177","type":"journal-article","created":{"date-parts":[[2015,4,27]],"date-time":"2015-04-27T06:25:18Z","timestamp":1430115918000},"page":"3875-3889","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Imidazole\u2010based alkaloid derivative\n LCB<\/scp>\n 54\u20100009 suppresses ocular angiogenesis and lymphangiogenesis in models of experimental retinopathy and corneal neovascularization"],"prefix":"10.1111","volume":"172","author":[{"given":"Byung\u2010Hak","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Dermatology College of Medicine The Catholic University of Korea Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyeop","family":"Lee","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Science and Engineering Korea Advanced Institute of Science and Technology (KAIST) Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun\u2010Sub","family":"Choi","sequence":"additional","affiliation":[{"name":"Catholic Institute for Visual Science Department of Ophthalmology and Visual Science College of Medicine The Catholic University of Korea Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae Young","family":"Park","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Science and Engineering Korea Advanced Institute of Science and Technology (KAIST) Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho Young","family":"Song","sequence":"additional","affiliation":[{"name":"LegoChem Biosciences, Inc. 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