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Molecular mechanisms of (R,R)ZX-5 on NO synthesis and its anti-angiogenic effect
Li Pan1, Jia-Liang Hu1, Wen-Jing Wang1
1State Key Laboratory of Natural Medicines, College of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
Abstract:
(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 Ca(2+) 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-Ca(2+)-eNOS pathways. Additionally, (R,R)ZX-5 can inhibit angiogenesis.
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