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

Junxiu Zhang; Ke Mao; Qing Gu; Xingwei Wu

doi:10.3389/fphar.2021.638215

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

Front Pharmacol. 2021 Mar 15:12:638215. doi: 10.3389/fphar.2021.638215. eCollection 2021.

Authors

Junxiu Zhang¹, Ke Mao², Qing Gu¹, Xingwei Wu¹

Affiliations

¹ Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Department of Ophthalmology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

Background: The purpose of this study is to investigate the antiangiogenic effect of Sanguinarine chloride (SC) on models of age-related macular degeneration (AMD) both in vivo and in vitro. Methods: 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. In vitro, 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) in vitro and laser induced VEGF expression in vivo were also analyzed. Results: SC (≤2.5 μM) was safe both in vitro and in vivo. 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. In vitro, SC inhibited VEGF-induced tube formation and endothelial cell migration by decreasing the phosphorylation of AKT, ERK1/2, and p38-MAPK in HRMECs. Conclusions: 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.

Keywords: age-related macula degeneration (AMD); angiogeneisis; choroidal neovascluarization; sanguinarine chloride; vascular endthelial growth factor (VEGF).