title: Aloe-emodin suppresses hypoxia-induced retinal angiogenesisviainhibition of HIF-1α/VEGF pathway.
abstract: Background: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.Methods:We established a vascular endothelial growth factor (VEGF) secretion model under chemical induced hypoxia by exposure of 150 µM CoCl2to 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. Forin vivostudy, 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.Results: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 invitroand prevents hypoxia-induced retinal neovascularizationin vivo.Conclusions: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.
authors.affiliation: Laboratory of Chinese Materia Medica, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China;; Post-Doctoral Research Station, KangHong Pharmaceutical Group, Chengdu, Sichuan 610036, China;; Post-Doctoral Mobile Station, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Wu
authors.affiliation: Post-Doctoral Research Station, KangHong Pharmaceutical Group, Chengdu, Sichuan 610036, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ke
authors.affiliation: Post-Doctoral Research Station, KangHong Pharmaceutical Group, Chengdu, Sichuan 610036, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Post-Doctoral Research Station, KangHong Pharmaceutical Group, Chengdu, Sichuan 610036, China.
authors.forename: Hongcheng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Post-Doctoral Research Station, KangHong Pharmaceutical Group, Chengdu, Sichuan 610036, China.
authors.forename: Na
authors.initials: N
authors.lastname: Ma
authors.affiliation: Post-Doctoral Research Station, KangHong Pharmaceutical Group, Chengdu, Sichuan 610036, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Fu
authors.affiliation: Post-Doctoral Research Station, KangHong Pharmaceutical Group, Chengdu, Sichuan 610036, China.
authors.forename: Manxi
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Post-Doctoral Research Station, KangHong Pharmaceutical Group, Chengdu, Sichuan 610036, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Gao
authors.affiliation: Post-Doctoral Research Station, KangHong Pharmaceutical Group, Chengdu, Sichuan 610036, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Hao
authors.affiliation: Post-Doctoral Mobile Station, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000627:therapeutic use*; D002460:Cell Line; D003035:Cobalt / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D000860:Hypoxia / Q000150:complications*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D000880:Anthraquinones; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D003035:Cobalt; C518327:aloe emodin; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; C018021:cobaltous chloride
keywords: Aloe-emodin; angiogenesis; hypoxia-inducible factor-1; oxygen-induced retinopathy.; vascular endothelial growth factor