title: Cnidium officinale extract and butylidenephthalide inhibits retinal neovascularization in vitro and in vivo.
abstract: BACKGROUND
  Retinal neovascularization, which is the pathological growth of new blood vessels, is associated with retinopathy of prematurity, neovascular age-related macular degeneration, diabetic retinopathy and retinal vein occlusion. In this study, we evaluated the effect of an extract of Cnidium officinale Makino (COE) and its bioactive compound, butylidenephthalide (BP), on the migration and tube formation of human umbilical vein endothelial cells (HUVECs), and on retinal pathogenic neovascularization in the oxygen-induced retinopathy (OIR) mouse model.
  
  
  METHODS
  The HUVECs were incubated with COE and BP (0.1-10 μg/ml). The mice were exposed to 75 % oxygen for 5 days starting on the 7(th) postnatal day (P7-P12). Then, the mice were returned to room air and intraperitoneally injected with COE (100 mg/kg) and BP (5 mg/kg) once per day for 5 days (P12-P16). On P17, we measured retinal neovascularization and analyzed the angiogenesis-related proteins expression using protein arrays.
  
  
  RESULTS
  COE and BP inhibit the HUVECs migration and the tube formation in a dose-dependent manner. In addition, COE significantly decreased retinal neovascularization in the OIR mice. COE reduced the expression levels of AREG, ANG, DLL4, Endostatin, IGFBP-2 and VEGF. Additionally, BP also inhibited the retinal neovascularization and down-regulated the expression of AREG, ANG, DLL4 and VEGF.
  
  
  CONCLUSIONS
  These results suggest that COE and BP exerts antiangiogenic effects on retinal neovascularization by inhibiting the expression of AREG, ANG, DLL4 and VEGF, indicating that antiangiogenic activities of COE may be in part due to its bioactive compound, BP.
authors.affiliation: Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseongdaero, Yuseong-gu, Daejeon, 34054, South Korea.
authors.forename: Yun Mi
authors.initials: YM
authors.lastname: Lee
authors.affiliation: Department of Biology, Chungnam National University, Daejeon, 34134, South Korea.
authors.forename: Yu-Ri
authors.initials: YR
authors.lastname: Lee
authors.affiliation: Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseongdaero, Yuseong-gu, Daejeon, 34054, South Korea.
authors.forename: Chan-Sik
authors.initials: CS
authors.lastname: Kim
authors.affiliation: Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseongdaero, Yuseong-gu, Daejeon, 34054, South Korea.
authors.forename: Kyuhyung
authors.initials: K
authors.lastname: Jo
authors.affiliation: Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseongdaero, Yuseong-gu, Daejeon, 34054, South Korea.
authors.forename: Eunjin
authors.initials: E
authors.lastname: Sohn
authors.affiliation: Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseongdaero, Yuseong-gu, Daejeon, 34054, South Korea.
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseongdaero, Yuseong-gu, Daejeon, 34054, South Korea. dvmhyun@kiom.re.kr.
authors.forename: Junghyun
authors.initials: J
authors.lastname: Kim
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D031048:Cnidium / Q000737:chemistry*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051379:Mice; D010796:Phthalic Anhydrides / Q000737:chemistry / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D015861:Retinal Neovascularization / Q000378:metabolism*; D012259:Ribonuclease, Pancreatic / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D010796:Phthalic Anhydrides; D010936:Plant Extracts; D042461:Vascular Endothelial Growth Factor A; C046366:angiogenin; D012259:Ribonuclease, Pancreatic; C026105:butylidenephthalide
keywords: Butylidenephthalide; Cnidium officinale; Oxygen-induced retinopathy; Retinal neovascularization; Vascular endothelial growth factor