The Antiangiogenic Effect of Sanguinarine Chloride on Experimental Choroidal Neovacularization in Mice via Inhibiting Vascular Endothelial Growth Factor

• Published in: Frontiers in pharmacology Vol. 12; p. 638215
• Main Authors: Zhang, Junxiu, Mao, Ke, Gu, Qing, Wu, Xingwei
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 15.03.2021
• Subjects: age-related macula degeneration (AMD); angiogeneisis; choroidal neovascluarization; Pharmacology; sanguinarine chloride; vascular endthelial growth factor (VEGF); age-related macula degeneration (AMD); choroidal neovascluarization; vascular endthelial growth factor (VEGF); angiogeneisis; sanguinarine chloride
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2021.638215

The purpose of this study is to investigate the antiangiogenic effect of Sanguinarine chloride (SC) on models of age-related macular degeneration (AMD) both and . Choroidal neovascularization (CNV) was conducted by laser photocoagulation in C57BL6/J mice. SC (2.5 μM, 2 μl/eye) was intravitreally injected immediately after laser injury. The control group received an equal amount of PBS. 7 days after laser injury, CNV severity was evaluated using fundus fluorescein angiography, hematoxylin and eosin (H&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. , 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) and laser induced VEGF expression were also analyzed. SC (≤2.5 μM) was safe both and . 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. , SC inhibited VEGF-induced tube formation and endothelial cell migration by decreasing the phosphorylation of AKT, ERK1/2, and p38-MAPK in HRMECs. 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.