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Constituents of Mediterranean Spices Counteracting Vascular Smooth Muscle Cell Proliferation: Identification and Characterization of Rosmarinic Acid Methyl Ester as a Novel Inhibitor
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SYSNO ASEP 0489017 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Constituents of Mediterranean Spices Counteracting Vascular Smooth Muscle Cell Proliferation: Identification and Characterization of Rosmarinic Acid Methyl Ester as a Novel Inhibitor Author(s) Liu, R. (CN)
Heiss, E.H. (AT)
Waltenberger, B. (AT)
Blažević, T. (AT)
Schachner, B. (DE)
Jiang, B. (CN)
Kryštof, Vladimír (UEB-Q) RID, ORCID
Liu, W. (CN)
Schwaiger, S. (AT)
Peña-Rodríguez, L. M. (MX)
Breuss, J. (AT)
Stuppner, H. (AT)
Dirsch, V.M. (AT)
Atanasov, A. G. (AT)Number of authors 14 Article number 1700860 Source Title Molecular Nutrition & Food Research. - : Wiley - ISSN 1613-4125
Roč. 62, č. 7 (2018)Number of pages 10 s. Language eng - English Country US - United States Keywords Mediterranean spices ; neointima formation ; rosmarinic acid ; rosmarinic acid methyl ester ; vascular smooth muscle cells Subject RIV CE - Biochemistry OECD category Biochemical research methods Institutional support UEB-Q - RVO:61389030 UT WOS 000429090900005 EID SCOPUS 85044510457 DOI 10.1002/mnfr.201700860 Annotation 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 IC 50 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 G 0 /G 1 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. Workplace Institute of Experimental Botany Contact David Klier, knihovna@ueb.cas.cz, Tel.: 220 390 469 Year of Publishing 2019
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