Isoliquiritigenin from licorice root suppressed neovascularisation in experimental ocular angiogenesis models.

摘要

AIM: To explore the antiangiogenic property of isoliquiritigenin (ISL) on in vivo and in vitro models. DESIGN: Laboratory investigation. METHODS: The effect of ISL on angiogenesis development was investigated using ex ovo chick chorioallantoic membrane model. Its effect on pathological angiogenesis was examined by (1) silver nitrate cauterisation-induced corneal neovascularisation in BALB/c mice, followed by topical ISL (0.2-50 muM) and CD31 immunofluorescence of corneal blood vessels; (2) argon laser photocoagulation-induced choroidal neovascularisation in C57BL/6 mice, followed by intravitreal ISL (10-200 muM) and fundus fluorescein angiography and immunofluorescence with Griffonia simplicifolia isolectin-B4 (GSA I-B4); and (3) oxygen-induced retinopathy in C57BL/6J mice pups, followed by intravitreal ISL (1-100 muM) and GSA I-B4 immunofluorescence. The vascular area was quantified and analysed by one-way analysis of variance and Student t test. Expression of vascular endothelial growth factor (VEGF) and pigment-epithelium-derived factor in human umbilical vein endothelial cells was analysed by western blotting. RESULTS: Ex ovo chick chorioallantoic membrane assay showed that ISL dose-dependently suppressed VEGF-induced vessel growth. In vivo experiments illustrated that topical ISL alleviated corneal neovascularisation (IC(50)=7.14 muM, day 7) and intravitreal ISL reduced vessel leakage and GSA I-B4-positive vascular area in choroidal and retinal neovascularisation. ISL was found to dose-dependently suppress VEGF and induce pigment epithelium derived factor expression in cultured endothelial cells. CONCLUSION: Using various experimental models of ocular neovascularisation, the authors have demonstrated that ISL from licorice extract has an antiangiogenic effect. The authors' findings suggest that ISL may be a potential antiangiogenic molecule in the development of therapy for neovascularisation diseases.