Document Detail

Rosmarinic acid suppresses retinal neovascularization via cell cycle arrest with increase of p21(WAF1) expression.
MedLine Citation:
PMID:  19470386     Owner:  NLM     Status:  MEDLINE    
Pathological angiogenesis is the most common cause of blindness at all ages including retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration. Despite advances in therapy, retinopathy of prematurity remains the most sight-threatening vaso-proliferative retinopathy in children. Herein, we demonstrated that rosmarinic acid has an anti-angiogenic activity to retinal neovascularization in a mouse model of retinopathy of prematurity, which is related to cell cycle arrest with increase of p21(WAF1). Rosmarinic acid significantly inhibited the proliferation of retinal endothelial cells in a dose-dependent manner, and inhibited in vitro angiogenesis of tube formation. Interestingly, the anti-proliferative activity of rosmarinic acid on retinal endothelial cells was related to G2/M phase cell cycle arrest in a dose-dependent manner. With treatment of rosmarinic acid, retinal endothelial cells in G2/M phase increased whereas those in G0/G1 and S phases decreased, which was accompanied by increase of p21(WAF1) expression in a dose-dependent manner. Moreover, rosmarinic acid effectively suppressed retinal neovascularization in a mouse model of retinopathy of prematurity, and showed no retinal toxicity. These data suggest rosmarinic acid could be a potent inhibitor of retinal neovascularization and may be applied in the treatment of other vasoproliferative retinopathies.
Jeong Hun Kim; Byung Joo Lee; Jin Hyoung Kim; Young Suk Yu; Min Young Kim; Kyu-Won Kim
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-05-24
Journal Detail:
Title:  European journal of pharmacology     Volume:  615     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-06-26     Completed Date:  2009-11-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  150-4     Citation Subset:  IM    
Department of Ophthalmology, College of Medicine, Seoul National University & Seoul Artificial Eye Center Clinical Research Institute, Seoul National University Hospital, Seoul 110-744, Republic of Korea.
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MeSH Terms
Angiogenesis Inhibitors / adverse effects,  pharmacology,  therapeutic use*
Cell Cycle / drug effects*
Cell Proliferation / drug effects
Cells, Cultured
Cinnamates / adverse effects,  pharmacology,  therapeutic use*
Cyclin-Dependent Kinase Inhibitor p21 / biosynthesis*
Depsides / adverse effects,  pharmacology,  therapeutic use*
Disease Models, Animal
Dose-Response Relationship, Drug
Infant, Newborn
Mice, Inbred C57BL
Retinal Neovascularization / drug therapy*,  metabolism*,  pathology
Retinopathy of Prematurity / drug therapy,  metabolism,  pathology
Reg. No./Substance:
0/Angiogenesis Inhibitors; 0/CDKN1A protein, human; 0/Cinnamates; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Depsides; 537-15-5/rosmarinic acid

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