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Aloe-emodin suppresses hypoxia-induced retinal angiogenesis inhibition of HIF-1α/VEGF pathway. | LitMetric

Aloe-emodin suppresses hypoxia-induced retinal angiogenesis inhibition of HIF-1α/VEGF pathway.

Int J Biol Sci

Post-Doctoral Mobile Station, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, China.

Published: October 2017

Aloe-emodin (AE) has been reported to possess the antiangiogenic effect on laser induced choroidal neovascularization. AE inhibits the vessel formation in the zebrafish embryos. However, it is still unclear whether AE can alleviate neovascularization. Here, we investigated the inhibitory effect of AE on the hypoxia-induced retinal neovascularization and the possible mechanisms. We established a vascular endothelial growth factor (VEGF) secretion model under chemical induced hypoxia by exposure of 150 µM CoCl to the ARPE-19 cells, then treated the cells with different concentrations of AE (0.2, 1.0 and 5.0 µg/mL) or a special hypoxia-inducible factor 1α (HIF-1α) inhibitor [3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole, YC-1, 1.0 µg/mL]. The cellular supernatants were collected 48 h later to measure the VEGFA concentrations by human VEGFA enzyme-linked immunosorbent assay (ELISA) kits, the mRNA expressions of VEGFA, HIF-1α and prolyl hydroxylase-2 (PHD-2) by quantitative reverse transcription-PCR (qRT-PCR) and the protein expressions of HIF-1α and PHD-2 by Western blots. For study, the rat pups with oxygen-induced retinopathy were treated with Conbercept ophthalmic injection (1.0 mg/kg) or AE (5.0 and 10.0 mg/kg) for five days, then the retinal avascular areas were assessed via visualization of the retinal vasculature with ADPase and hematoxylin & eosin (H&E) stains. AE inhibits the VEGFA secretion of ARPE-19 cells under hypoxia condition, decreases the mRNA expressions of VEGFA and PHD-2 and the protein expressions of VEGFA, HIF-1α and PHD-2 in and prevents hypoxia-induced retinal neovascularization AE ameliorates retinal neovascularization throuth inhibition of the HIF-1α/VEGF signaling pathway. AE may be developed as a potential drug for the prevention and treatment of diabetic retinopathy.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5118782PMC
http://dx.doi.org/10.7150/ijbs.16334DOI Listing

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