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

被引:34
|
作者
Wu, Jianming [1 ,2 ,3 ]
Ke, Xiao [2 ]
Fu, Wei [2 ]
Gao, Xiaoping [2 ]
Zhang, Hongcheng [2 ]
Wang, Wei [2 ]
Ma, Na [2 ]
Zhao, Manxi [2 ]
Hao, Xiaofeng [2 ]
Zhang, Zhirong [3 ]
机构
[1] Southwest Med Univ, Sch Pharm, Dept Pharmacol, Lab Chinese Mat Med, Luzhou 646000, Sichuan, Peoples R China
[2] KangHong Pharmaceut Grp, Postdoctoral Res Stn, Chengdu 610036, Sichuan, Peoples R China
[3] Sichuan Univ, West China Sch Pharm, Postdoctoral Mobile Stn, Chengdu 610041, Sichuan, Peoples R China
关键词
specnuezhenide; angiogenesis; hypoxia-inducible factor-1; oxygen-induced retinopathy; vascular endothelial growth factor; ACID-ENRICHED EXTRACT; OLEANOLIC ACID; UP-REGULATION; SECOIRIDOID GLUCOSIDES; DIABETIC RETINA; DOWN-REGULATION; FRUIT EXTRACT; FACTOR-I; HIF-1; NEOVASCULARIZATION;
D O I
10.3390/molecules21121756
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Specnuezhenide (SPN), one of the main ingredients of Chinese medicine "Nu-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 mu M CoCl2 to the cells and determined the VEGFA concentrations, the mRNA expressions of VEGFA, hypoxia inducible factor-1 alpha (HIF-1 alpha) & prolyl hydroxylases 2 (PHD-2), and the protein expressions of HIF-1 alpha and PHD-2 after treatment of 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1, 1.0 mu g/mL) or SPN (0.2, 1.0 and 5.0 mu g/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-1 alpha 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-1 alpha/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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页数:15
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