title: Molecular mechanisms of (R,R)ZX-5 on NO synthesis and its anti-angiogenic effect.
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.
authors.affiliation: State Key Laboratory of Natural Medicines, College of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Li
authors.initials: L
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Natural Medicines, College of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jia-Liang
authors.initials: JL
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Natural Medicines, College of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, College of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural Medicines, College of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Natural Medicines, College of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Zhen-Dong
authors.initials: ZD
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, University of China Pharmaceutical, Nanjing 210009, China.
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural Medicines, College of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Han-Mei
authors.initials: HM
authors.lastname: Xu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000187:drug effects / Q000378:metabolism; D002829:Choroid / Q000098:blood supply / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011817:Rabbits; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014966:Xanthenes / Q000378:metabolism
chemical_list: C480782:1-phenyl-3-(3-methoxy-2-propoxy-5-(4-(3,4,5-trimethoxyphenyl)-1,3-dithiolane-2-yl)phenyl)thiourea; D020533:Angiogenesis Inhibitors; D000814:Aniline Compounds; D014966:Xanthenes; D019938:Cyclin D1; C059715:Fluo-3; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D013890:Thiourea; D002118:Calcium