Constituents of Mediterranean Spices Counteracting Vascular Smooth Muscle Cell Proliferation: Identification and Characterization of Rosmarinic Acid Methyl Ester as a Novel Inhibitor
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- Keywords
- Mediterranean spices, neointima formation, rosmarinic acid, rosmarinic acid methyl ester, vascular smooth muscle cells,
- MeSH
- Endothelium, Vascular cytology drug effects pathology MeSH
- Cinnamates administration & dosage adverse effects pharmacology therapeutic use MeSH
- Depsides administration & dosage adverse effects pharmacology therapeutic use MeSH
- Human Umbilical Vein Endothelial Cells cytology MeSH
- Phosphorylation drug effects MeSH
- Cardiovascular Agents adverse effects pharmacology therapeutic use MeSH
- Spices analysis MeSH
- Rats MeSH
- Cells, Cultured MeSH
- Rosmarinic Acid MeSH
- Humans MeSH
- Methylation MeSH
- Mice, Inbred C57BL MeSH
- Random Allocation MeSH
- Neovascularization, Pathologic metabolism pathology prevention & control MeSH
- Protein Processing, Post-Translational drug effects MeSH
- Cell Proliferation drug effects MeSH
- Retinoblastoma Protein metabolism MeSH
- Rosmarinus chemistry growth & development MeSH
- Diet, Mediterranean MeSH
- Muscle, Smooth, Vascular cytology drug effects metabolism pathology MeSH
- Cell Survival drug effects MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Mediterranean Region MeSH
- Names of Substances
- Cinnamates MeSH
- Depsides MeSH
- Cardiovascular Agents MeSH
- Retinoblastoma Protein MeSH
- rosmarinic acid methyl ester MeSH Browser
SCOPE: Aberrant vascular smooth muscle cell (VSMC) proliferation is involved in atherosclerotic plaque formation and restenosis. Mediterranean spices have been reported to confer cardioprotection, but their direct influence on VSMCs has largely not been investigated. This study aims at examining rosmarinic acid (RA) and 11 related constituents for inhibition of VSMC proliferation in vitro, and at characterizing the most promising compound for their mode of action and influence on neointima formation in vivo. METHODS AND RESULTS: RA, rosmarinic acid methyl ester (RAME), and caffeic acid methyl ester inhibit VSMC proliferation in a resazurin conversion assay with IC50 s of 5.79, 3.12, and 6.78 µm, respectively. RAME significantly reduced neointima formation in vivo in a mouse femoral artery cuff model. Accordingly, RAME leads to an accumulation of VSMCs in the G0 /G1 cell-cycle phase, as indicated by blunted retinoblastoma protein phosphorylation upon mitogen stimulation and inhibition of cyclin-dependent kinase 2 in vitro. CONCLUSION: RAME represses PDGF-induced VSMC proliferation in vitro and reduces neointima formation in vivo. These results recommend RAME as an interesting compound with VSMC-inhibiting potential. Future metabolism and pharmacokinetics studies might help to further evaluate the potential relevance of RAME and other spice-derived polyphenolics for vasoprotection.
Department of Pharmacognosy University of Vienna Vienna Austria
Institute of Genetics and Animal Breeding of the Polish Academy of Sciences Jastrzebiec Poland
Unidad de Biotecnología Centro de investigación Científica de Yucatán Mérida México
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