Inhibition of Hypoxia-Induced Retinal Angiogenesis by Specnuezhenide, an Effective Constituent of Ligustrum lucidum Ait., through Suppression of the HIF-1α/VEGF Signaling Pathway

Autor: Jianming Wu, Xiao Ke, Wei Fu, Xiaoping Gao, Hongcheng Zhang, Wei Wang, Na Ma, Manxi Zhao, Xiaofeng Hao, Zhirong Zhang
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Molecules, Vol 21, Iss 12, p 1756 (2016)
Druh dokumentu: article
ISSN: 1420-3049
DOI: 10.3390/molecules21121756
Popis: Specnuezhenide (SPN), one of the main ingredients of Chinese medicine “Nü-zhen-zi”, has anti-angiogenic and vision improvement effects. However, studies of its effect on retinal neovascularization are limited so far. In the present study, we established a vascular endothelial growth factor A (VEGFA) secretion model of human acute retinal pigment epithelial-19 (ARPE-19) cells by exposure of 150 μM CoCl2 to the cells and determined the VEGFA concentrations, the mRNA expressions of VEGFA, hypoxia inducible factor-1α (HIF-1α) & prolyl hydroxylases 2 (PHD-2), and the protein expressions of HIF-1α and PHD-2 after treatment of 3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1, 1.0 μg/mL) or SPN (0.2, 1.0 and 5.0 μg/mL). Furthermore, rat pups with retinopathy were treated with SPN (5.0 and 10.0 mg/kg) in an 80% oxygen atmosphere and the retinal avascular areas were assessed through visualization using infusion of ADPase and H&E stains. The results showed that SPN inhibited VEGFA secretion by ARPE-19 cells under hypoxia condition, down-regulated the mRNA expressions of VEGFA and PHD-2 slightly, and the protein expressions of VEGFA, HIF-1α and PHD-2 significantly in vitro. SPN also prevented hypoxia-induced retinal neovascularization in a rat model of oxygen-induced retinopathy in vivo. These results indicate that SPN ameliorates retinal neovascularization through inhibition of HIF-1α/VEGF signaling pathway. Therefore, SPN has the potential to be developed as an agent for the prevention and treatment of diabetic retinopathy.
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