Jianyi Cui1, Rui Gong2, Shuiqing Hu2, Ling Cai2, Lei Chen3. 1. Department of Ophthalmology, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning, People's Republic of China. 2. Department of Ophthalmology, The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, Liaoning, People's Republic of China. 3. Department of Ophthalmology, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning, People's Republic of China. Electronic address: iamdoctorchen@163.com.
Abstract
AIMS: Gambogic acid (GA) is one of active components of Chinese medicine gamboges resin. Diabetic retinopathy (DR) is a most serious microvascular complication of diabetes and also the leading cause of blindness. The aim of this study is to evaluate the beneficial effect of GA on diabetes-induced retinal angiogenesis and further explore the potential mechanisms. MATERIAL AND METHODS: High glucose (HG)-treated RF/6A cells and STZ-induced diabetic mice were used as in vitro and in vivo models. Then the effects of GA on proliferation, migration and tube formation in RF/6A cells and pathomorphological changes in STZ-induced diabetic mice were determined. The activation of HIF-1α/VEGF and PI3K/AKT signaling pathways was assessed by various molecular biological experiments. KEY FINDINGS: According to our results, GA inhibited HG-induced proliferation, migration and tube formation in choroid-retinal endothelial RF/6A cells. The upregulation of HIF-1α and VEGF induced by HG in RF/6A cells was restrained by GA treatment significantly. Moreover, GA suppressed retinal pathomorphological changes and angiogenesis in STZ-induced diabetic mice in vivo, and also inhibited the activation of HIF-1α/VEGF pathway induced by diabetics. Finally, GA suppressed the activation of PI3K/AKT signaling pathway in STZ-induced diabetic mice in vivo and in HG-induced RF/6A cells in vitro. Further activation of PI3K/AKT pathway by IGF-1 restrained the beneficial effect of GA in RF/6A cells. SIGNIFICANCE: Our results provide evidence that GA may ameliorate diabetes-induced retinal angiogenesis, which are proofs that GA may be developed as a potential drug for treating DR.
AIMS: Gambogic acid (GA) is one of active components of Chinese medicine gamboges resin. Diabetic retinopathy (DR) is a most serious microvascular complication of diabetes and also the leading cause of blindness. The aim of this study is to evaluate the beneficial effect of GA on diabetes-induced retinal angiogenesis and further explore the potential mechanisms. MATERIAL AND METHODS: High glucose (HG)-treated RF/6A cells and STZ-induced diabeticmice were used as in vitro and in vivo models. Then the effects of GA on proliferation, migration and tube formation in RF/6A cells and pathomorphological changes in STZ-induced diabeticmice were determined. The activation of HIF-1α/VEGF and PI3K/AKT signaling pathways was assessed by various molecular biological experiments. KEY FINDINGS: According to our results, GA inhibited HG-induced proliferation, migration and tube formation in choroid-retinal endothelial RF/6A cells. The upregulation of HIF-1α and VEGF induced by HG in RF/6A cells was restrained by GA treatment significantly. Moreover, GA suppressed retinal pathomorphological changes and angiogenesis in STZ-induced diabeticmice in vivo, and also inhibited the activation of HIF-1α/VEGF pathway induced by diabetics. Finally, GA suppressed the activation of PI3K/AKT signaling pathway in STZ-induced diabeticmice in vivo and in HG-induced RF/6A cells in vitro. Further activation of PI3K/AKT pathway by IGF-1 restrained the beneficial effect of GA in RF/6A cells. SIGNIFICANCE: Our results provide evidence that GA may ameliorate diabetes-induced retinal angiogenesis, which are proofs that GA may be developed as a potential drug for treating DR.
Authors: Jinbo Sun; Zhining Zhao; Wei Zhang; Qisheng Tang; Fan Yang; Xiangnan Hu; Chong Liu; Bin Song; Bo Zhang; He Wang Journal: Med Sci Monit Date: 2020-03-02