Constituents of Mediterranean Spices Counteracting Vascular Smooth Muscle Cell Proliferation: Identification and Characterization of Rosmarinic Acid Methyl Ester as a Novel Inhibitor

0489017 - ÚEB 2019 RIV US eng J - Journal Article
Liu, R. - Heiss, E.H. - Waltenberger, B. - Blažević, T. - Schachner, B. - Jiang, B. - Kryštof, Vladimír - Liu, W. - Schwaiger, S. - Peña-Rodríguez, L. M. - Breuss, J. - Stuppner, H. - Dirsch, V.M. - Atanasov, A. G.
Constituents of Mediterranean Spices Counteracting Vascular Smooth Muscle Cell Proliferation: Identification and Characterization of Rosmarinic Acid Methyl Ester as a Novel Inhibitor.
Molecular Nutrition & Food Research. Roč. 62, č. 7 (2018), č. článku 1700860. ISSN 1613-4125. E-ISSN 1613-4133
Institutional support: RVO:61389030
Keywords : Mediterranean spices * neointima formation * rosmarinic acid * rosmarinic acid methyl ester * vascular smooth muscle cells
OECD category: Biochemical research methods
Impact factor: 4.653, year: 2018

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.
Permanent Link: http://hdl.handle.net/11104/0283506