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Vishal Jhanji, Huanming Liu, Kasin Law, Vincent Y. Lee, Shao-Fen Huang, Chi-Pui Pang, Gary H. Yam; Natural Herbal Chemicals For Anti-angiogenesis In Eye. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4893.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the anti-angiogenic property of isoliquiritigenin by a systematic strategy of in vivo and in vitro models.
Isoliquiritigenin (2-50 µM), Avastin (1 µg/ml) and vascular endothelial growth factor (VEGF, 100 ng/ml) were added to collagen-nylon mesh placed on chick chorioallantoic membrane (CAM) and the meshes with blood vessel ingrowth were quantified. Silver nitrate cauterization-induced corneal neovascularization in BALB/c mice was treated with topical ISL (0.2-50 µM) or balanced salt solution (BSS) 4 times daily and examined by immunostaining for CD31. Argon laser photocoagulation-induced choroidal neovascularization in C57BL/6 mice was treated by intravitreal isoliquiritigenin (10-200 µM), anti-VEGF monoclonal antibody or BSS and monitored by fundus fluorescein angiography. The severity of leakage was scored and choroid was immunostained with Griffonia simplicifolia isolectin-B4. Oxygen-induced retinopathy in C57BL/6J mouse pups was treated with intravitreal isoliquiritigenin (1-100 µM) or BSS, examined by isolectin-B4 staining and percentage of vascular area was quantified. The effect of ISL on VEGF signaling in human umbilical vein endothelial cells (HUVEC) was analyzed by western blotting.
Isoliquiritigenin dose-dependently suppressed VEGF-induced blood vessel growth in chick CAM. The progression of corneal neovascularization was suppressed by topical isoliquiritigenin (optimal dose at 10 µM and IC50 = 7.14 µM at day 7). Similarly, intravitreal isoliquiritigenin reduced choroidal and retinal neovascularisation. ISL down-regulated VEGF and up-regulated pigment epithelial growth factor expression in cultured HUVEC.
Our results showed that isoliquiritigenin has anti-angiogenic properties probably mediated through pro- and anti-angiogenic factor levels.
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