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Int. J. Mol. Sci. 2012, 13(3), 2717-2726; doi:10.3390/ijms13032717

Molecular Mechanisms of (R,R)ZX-5 on NO Synthesis and Its Anti-Angiogenic Effect

State Key Laboratory of Natural Medicines, College of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China
Department of Pharmacy, University of China Pharmaceutical, Nanjing 210009, China
Authors to whom correspondence should be addressed.
Received: 24 November 2011 / Revised: 4 February 2012 / Accepted: 14 February 2012 / Published: 29 February 2012
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(R,R)ZX-5 is a NO regulatory compound, which could significantly increase choroidal blood flow in New Zealand rabbit. The aim of this paper is to investigate the molecular mechanism of (R,R)ZX-5 promoting NO production. Besides this, we also investigated the antiangiogenic activity of (R,R)ZX-5. Analysis of Western blot showed that (R,R)ZX-5 up-regulated the expression of Akt, p-Akt (Thr473), eNOS and p-eNOS (Ser1177), down-regulated the expression of Cyclin D1 in human retinal endothelial cells and escalated the intracellular free Ca2+ concentration. Additionally, (R,R)ZX-5 inhibited the growth of blood vessels in the chick chorioallantoic membrane model. It is concluded that (R,R)ZX-5 promotes choroidal blood flow through PI3K/Akt-eNOS and Akt-Ca2+-eNOS pathways. Additionally, (R,R)ZX-5 can inhibit angiogenesis.
Keywords: (R,R)ZX-5; age-related macular degeneration; choroidal neovascularization; signal pathways; angiogenesis (R,R)ZX-5; age-related macular degeneration; choroidal neovascularization; signal pathways; angiogenesis
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Pan, L.; Hu, J.-L.; Wang, W.-J.; Zhang, X.-J.; Wei, J.; Liu, Z.-D.; Zhang, Y.-H.; Xu, H.-M. Molecular Mechanisms of (R,R)ZX-5 on NO Synthesis and Its Anti-Angiogenic Effect. Int. J. Mol. Sci. 2012, 13, 2717-2726.

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