Gambogic acid ameliorates diabetes-induced proliferative retinopathy through inhibition of the HIF-1α/VEGF expressionviatargeting PI3K/AKT pathway

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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.

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