{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:31:56Z","timestamp":1789011116253,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,3,30]],"date-time":"2018-03-30T00:00:00Z","timestamp":1522368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81603326"],"award-info":[{"award-number":["81603326"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["P25971\u2010B23"],"award-info":[{"award-number":["P25971\u2010B23"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:sec><jats:title>Scope<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>RA, rosmarinic acid methyl ester (RAME), and caffeic acid methyl ester inhibit VSMC proliferation in a resazurin conversion assay with IC<jats:sub>50<\/jats:sub>s of 5.79, 3.12, and 6.78\u00a0\u00b5<jats:sc>m<\/jats:sc>, 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<jats:sub>0<\/jats:sub>\/G<jats:sub>1<\/jats:sub> cell\u2010cycle phase, as indicated by blunted retinoblastoma protein phosphorylation upon mitogen stimulation and inhibition of cyclin\u2010dependent kinase 2 in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>RAME represses PDGF\u2010induced VSMC proliferation in vitro and reduces neointima formation in vivo. These results recommend RAME as an interesting compound with VSMC\u2010inhibiting potential. Future metabolism and pharmacokinetics studies might help to further evaluate the potential relevance of RAME and other spice\u2010derived polyphenolics for vasoprotection.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.201700860","type":"journal-article","created":{"date-parts":[[2018,2,5]],"date-time":"2018-02-05T14:35:03Z","timestamp":1517841303000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Constituents of Mediterranean Spices Counteracting Vascular Smooth Muscle Cell Proliferation: Identification and Characterization of Rosmarinic Acid Methyl Ester as a Novel Inhibitor"],"prefix":"10.1002","volume":"62","author":[{"given":"Rongxia","family":"Liu","sequence":"first","affiliation":[{"name":"School of Pharmacy Key Laboratory of Molecular Pharmacology and Drug Evaluation Ministry of Education Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong University of Yantai  Yantai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke H.","family":"Heiss","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Waltenberger","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy\/Pharmacognosy and Center for Molecular Biosciences Innsbruck (CMBI) University of Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Bla\u017eevi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Schachner","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baohong","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Krystof","sequence":"additional","affiliation":[{"name":"Laboratory of Growth Regulators Palacky University &amp; Institute of Experimental Botany AS CR  Olomouc Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanhui","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy Key Laboratory of Molecular Pharmacology and Drug Evaluation Ministry of Education Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong University of Yantai  Yantai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Schwaiger","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy\/Pharmacognosy and Center for Molecular Biosciences Innsbruck (CMBI) University of Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis M.","family":"Pe\u00f1a\u2010Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Unidad de Biotecnolog\u00eda Centro de investigaci\u00f3n Cient\u00edfica de Yucat\u00e1n  M\u00e9rida M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes M.","family":"Breuss","sequence":"additional","affiliation":[{"name":"Center for Physiology and Pharmacology Institute for Vascular Biology and Thrombosis Research Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Stuppner","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy\/Pharmacognosy and Center for Molecular Biosciences Innsbruck (CMBI) University of Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena M.","family":"Dirsch","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2545-0967","authenticated-orcid":false,"given":"Atanas G.","family":"Atanasov","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy University of Vienna  Vienna Austria"},{"name":"Institute of Genetics and Animal Breeding of the Polish Academy of Sciences  Jastrzebiec Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,3,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/0267659112452316"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1042\/cs0870467"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01323"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2015.02.002"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.12466"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00394-015-1092-x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2013.805713"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf051513y"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2015.08.001"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E08-06-0569"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-011-0317-0"},{"key":"e_1_2_8_13_1","unstructured":"V.Pieri Ph.D. thesis University of Innsbruck (Innsbruck Austria)2011."},{"key":"e_1_2_8_14_1","first-page":"1319","volume":"9","author":"Zapata\u2010Estrella H. E.","year":"2014","journal-title":"Nat. Prod. Comm."},{"key":"e_1_2_8_15_1","first-page":"1473","volume":"12","author":"Escalante\u2010Erosa F.","year":"2017","journal-title":"Nat. Prod. Comm."},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02492002"},{"key":"e_1_2_8_17_1","unstructured":"M.H\u00e4user Ph.D. thesis University of Innsbruck (Innsbruck Austria)2001."},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/pca.917"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2005.03.002"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0035-1565286"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201400791"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.110.212654"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules201119703"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12558"},{"key":"e_1_2_8_25_1","volume":"61","author":"Wang L.","year":"2017","journal-title":"Mol. Nutr. Food Res."},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep20771"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jnatprod.7b00268"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2016.05.002"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2015.03.030"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-11-0366"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0168092"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5293.1672"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.10.5.488"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1278-3218(01)00087-7"},{"key":"e_1_2_8_35_1","first-page":"19","volume":"5","author":"Boehm M.","year":"2003","journal-title":"Prog. Cell Cycle Res."},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules21081083"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/604536"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2017.01.016"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1080\/09168451.2015.1010478"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6RA28237G"}],"container-title":["Molecular Nutrition &amp; Food Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmnfr.201700860","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mnfr.201700860","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T07:35:49Z","timestamp":1695540949000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mnfr.201700860"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,30]]},"references-count":39,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2018,4]]}},"alternative-id":["10.1002\/mnfr.201700860"],"URL":"https:\/\/doi.org\/10.1002\/mnfr.201700860","archive":["Portico"],"relation":{},"ISSN":["1613-4125","1613-4133"],"issn-type":[{"value":"1613-4125","type":"print"},{"value":"1613-4133","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,30]]},"assertion":[{"value":"2017-10-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"1700860"}}