Abstract

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.

Full text access

Liu R, Heiss EH, Waltenberger B, Blažević T, Schachner D, Jiang B, Krystof V, Liu W, Schwaiger S, Peña-Rodríguez LM, Breuss JM, Stuppner H, Dirsch VM, Atanasov AG. Mol Nutr Food Res. 2018 Feb 5:e1700860. doi: 10.1002/mnfr.201700860. PubMed PMID: 29405576.

Keywords: Mediterranean spices; neointima formation; rosmarinic acid; rosmarinic acid methyl ester; Mediterranean spices bioactivities; vascular smooth muscle cells, cell proliferation; cyclin-dependent kinase 2; rosmarinic acid methyl ester as inhibitor of vascular smooth muscle cell proliferation.

Tropical rainforest, Queensland, Australia. Photo by Dr. Rohan Davis.

Analytical equipment. Photo by Atanas G. Atanasov.

Hep-2 signal activated cells. Image by Dr. Vassilis Doucas.

Flower blossoms at gardens by the bay Singapore-photo by Dr. Hemanth Kumar Boyina.

Saffron plants, Zapponeta (Foggia), South of Italy. Photo by Dr. Grazia D'Onofrio.

Blood cells colored with fluorescence dye. Photo by Dr. Davide Barreca.

Substance library. Photo by Dr. Nikolay Tzvetkov.

Lichens of the Eastern Morocco, Oujda, Morocco. Photo by Dr. Khalid El Bairi ©.

The Botanical Garden of Department of Pharmacognosy, University of Vienna, Austria. Photo by Atanas G. Atanasov.

Lagoon of the seven cities, a twin lake in the crater of a dormant volcano in the western part of the São Miguel island (Azores, Portugal). Photo by Dr. Ana Sanches Silva.

Central Australian desert scene. Photo by Dr. Rohan Davis.

HEK293T cells. Photo by Atanas G. Atanasov.

Tropical rainforest, Queensland, Australia. Photo by Dr. Rohan Davis.

Australian ocean scene. Photo by Dr. Rohan Davis.

Laboratory equipment. Photo by Atanas G. Atanasov.

Rhododendron arboreum flower. Photo by Devesh Tewari.

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Euphorbia prolifera Buch. (Ham) Ex. Photo by Devesh Tewari.

Foothills of Himalaya, India. Photo by Devesh Tewari.

The Valley of Flowers, Himalaya, India. Photo by Dr. Rajeshwari Singh.

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Polygonum maritimum (L.) (Polygonaceae)- Ourdania beach (Ain Temouchent- west Algeria)- taken by PhD. EL HACI Imad Abdelhamid

Flower blossoms at gardens by the bay Singapore-photo by Dr. Hemanth Kumar Boyina.

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