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

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

  • Molecules. 2016 Dec 21;21(12):1756. doi: 10.3390/molecules21121756.
Jianming Wu 1 2 3,  Xiao Ke 4,  Wei Fu 5,  Xiaoping Gao 6,  Hongcheng Zhang 7,  Wei Wang 8,  Na Ma 9,  Manxi Zhao 10,  Xiaofeng Hao 11,  Zhirong Zhang 12
Affiliations

Affiliations

  • 1 Laboratory of Chinese Materia Medica, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, China. jianmingwu@swmu.edu.cn.
  • 2 Post-Doctoral Research Station, KangHong Pharmaceutical Group, Chengdu 610036, Sichuan, China. jianmingwu@swmu.edu.cn.
  • 3 Post-Doctoral Mobile Station, West China School of Pharmacy, Sichuan University, Chengdu 610041, Sichuan, China. jianmingwu@swmu.edu.cn.
  • 4 Post-Doctoral Research Station, KangHong Pharmaceutical Group, Chengdu 610036, Sichuan, China. kexiao@cnkh.com.
  • 5 Post-Doctoral Research Station, KangHong Pharmaceutical Group, Chengdu 610036, Sichuan, China. fu_wei99@163.com.
  • 6 Post-Doctoral Research Station, KangHong Pharmaceutical Group, Chengdu 610036, Sichuan, China. 1483687108@qq.com.
  • 7 Post-Doctoral Research Station, KangHong Pharmaceutical Group, Chengdu 610036, Sichuan, China. arken20@163.com.
  • 8 Post-Doctoral Research Station, KangHong Pharmaceutical Group, Chengdu 610036, Sichuan, China. dy_ts110@163.com.
  • 9 Post-Doctoral Research Station, KangHong Pharmaceutical Group, Chengdu 610036, Sichuan, China. manapppp@163.com.
  • 10 Post-Doctoral Research Station, KangHong Pharmaceutical Group, Chengdu 610036, Sichuan, China. zhaomanqian@cnkh.com.
  • 11 Post-Doctoral Research Station, KangHong Pharmaceutical Group, Chengdu 610036, Sichuan, China. hxf@cnkh.com.
  • 12 Post-Doctoral Mobile Station, West China School of Pharmacy, Sichuan University, Chengdu 610041, Sichuan, China. zrzzl@vip.sina.com.
PMID: 28009852 DOI: 10.3390/molecules21121756
Abstract

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.

Keywords

angiogenesis; hypoxia-inducible factor-1; oxygen-induced retinopathy; specnuezhenide; vascular endothelial growth factor.

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