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Pharmacol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> The purpose of this study is to investigate the antiangiogenic effect of Sanguinarine chloride (SC) on models of age-related macular degeneration (AMD) both <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Choroidal neovascularization (CNV) was conducted by laser photocoagulation in C57BL6\/J mice. SC (2.5\u00a0\u03bcM, 2\u00a0\u03bcl\/eye) was intravitreally injected immediately after laser injury. The control group received an equal amount of PBS. 7\u00a0days after laser injury, CNV severity was evaluated using fundus fluorescein angiography, hematoxylin and eosin (H&amp;amp;E) staining, and choroid flat-mount staining. Vascular endothelial growth factor (VEGF) expression in the retina\/choroid complex was measured by western blot analysis and ELISA kit. <jats:italic>In vitro<\/jats:italic>, human retinal microvascular endothelial cells (HRMECs) were used to investigate the effects of SC on cell tube formation, migration, and cytotoxicity. The expression of VEGF-induced expression of extracellular signal-regulated kinase (ERK)1\/2, protein kinase B (AKT), mitogen-activated protein kinases (p38-MAPK) <jats:italic>in vitro<\/jats:italic> and laser induced VEGF expression <jats:italic>in vivo<\/jats:italic> were also analyzed.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> SC (\u22642.5\u00a0\u03bcM) was safe both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Intravitreal injection of SC restrained the formation of laser induced CNV in mice and decreased VEGF expression in the laser site of the retina\/choroid complex. <jats:italic>In vitro<\/jats:italic>, SC inhibited VEGF-induced tube formation and endothelial cell migration by decreasing the phosphorylation of AKT, ERK1\/2, and p38-MAPK in HRMECs.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> SC could inhibit laser-induced CNV formation via down-regulating VEGF expression and restrain the VEGF-induced tube formation and endothelial migration. Therefore, SC could be a potential candidate for the treatment of wet AMD.<\/jats:p>","DOI":"10.3389\/fphar.2021.638215","type":"journal-article","created":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T04:27:16Z","timestamp":1615782436000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["The Antiangiogenic Effect of Sanguinarine Chloride on Experimental Choroidal Neovacularization in Mice via Inhibiting Vascular Endothelial Growth Factor"],"prefix":"10.3389","volume":"12","author":[{"given":"Junxiu","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Mao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Gu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingwei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"933","DOI":"10.4155\/fmc-2017-0041","article-title":"Anticancer potential of sanguinarine for various human malignancies","volume":"9","author":"Achkar","year":"2017","journal-title":"Future Med. 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