{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T23:04:50Z","timestamp":1789513490867,"version":"build-2803163510"},"reference-count":53,"publisher":"Georg Thieme Verlag KG","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Drug Res (Stuttg)"],"abstract":"<jats:title>Purpose<\/jats:title>\n                  <jats:p>Enhanced glycolytic activity drives vascular smooth muscle cell proliferation and\n                    migration. Pyruvate kinase M2, a key glycolytic enzyme, modulates cancer cell\n                    proliferation. Shikonin, an inhibitor of pyruvate kinase M2, exerts\n                    anti-proliferative effects on cancer cells; still, its involvement in vascular\n                    smooth muscle cell proliferation and neointimal hyperplasia is not established.\n                    We investigated the effects of shikonin on platelet-derived growth\n                    factor-BB\u2013induced changes in vascular smooth muscle cell function and neointimal\n                    hyperplasia. Methods: Murine aortic vascular smooth muscle cells were pretreated\n                    with shikonin and stimulated with platelet-derived growth factor-BB. Wire injury\n                    of the carotid artery was performed in C57Bl\/J6 mice to induce neointimal\n                    hyperplasia. Results: Our study observes a marked upregulation of pyruvate\n                    kinase M2 in platelet-derived growth factor-BB stimulated vascular smooth muscle\n                    cells. Shikonin inhibited pyruvate kinase M2 expression and effectively reduced\n                    platelet-derived growth factor-BB\u2013induced vascular smooth muscle cell\n                    proliferation and migration and also favoured the contractile vascular smooth\n                    muscle cell phenotype. Expression of matrix metalloproteinase-2 and\n                    interleukin-6 messenger RNAs was significantly lower in shikonin-treated\n                    vascular smooth muscle cells as compared to platelet-derived growth\n                    factor-BB\u2013treated control. Pyruvate kinase M2 translocated to the mitochondria\n                    and pyruvate kinase M2 inhibition via shikonin promoted mitochondrial reactive\n                    oxygen species levels, increased oxidative stress and induced vascular smooth\n                    muscle cell apoptosis. Perivascular application of shikonin suppressed\n                    neointimal hyperplasia. Conclusion: Our findings indicate that shikonin\n                    suppresses vascular smooth muscle cell proliferation and migration, thereby\n                    limiting neointimal hyperplasia and potentially serving as a novel therapeutic\n                    strategy for atherosclerosis and restenosis.<\/jats:p>","DOI":"10.1055\/a-2945-2736","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T22:57:27Z","timestamp":1789513047000},"source":"Crossref","is-referenced-by-count":0,"title":["Shikonin inhibits Vascular Smooth Muscle Cell Phenotypic Modulation\n                    and attenuates Neointimal Hyperplasia"],"prefix":"10.1055","author":[{"given":"Ankan","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Panjab University, Chandigarh, India","place":["Chandigarh"],"department":["University Institute of Pharmaceutical Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakeel","family":"Ahmed","sequence":"additional","affiliation":[{"name":"National Institute of Pharmaceutical Education and\n                    Research, PB, India","place":["Sahibzada Ajit Singh Nagar"],"department":["Department of Pharmacology and Toxicology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Singh","sequence":"additional","affiliation":[{"name":"Panjab University, Chandigarh, India","place":["Chandigarh"],"department":["University Institute of Pharmaceutical Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyam Sunder","family":"Sharma","sequence":"additional","affiliation":[{"name":"National Institute of Pharmaceutical Education and\n                    Research, PB, India","place":["Sahibzada Ajit Singh Nagar"],"department":["Department of Pharmacology and Toxicology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanwaljit","family":"Chopra","sequence":"additional","affiliation":[{"name":"Panjab University, Chandigarh, India","place":["Chandigarh"],"department":["University Institute of Pharmaceutical Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7263-9829","authenticated-orcid":false,"given":"Manish","family":"Jain","sequence":"additional","affiliation":[{"name":"Panjab University, Chandigarh, India","place":["Chandigarh"],"department":["University Institute of Pharmaceutical Sciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s12872-016-0445-6","article-title":"Effect of diabetes mellitus on long-term outcomes after repeat drug-eluting\n                    stent implantation for in-stent 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Jain","year":"2021","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"926945","DOI":"10.3389\/fphar.2022.926945","article-title":"Shikonin ameliorated mice colitis by inhibiting dimerization and tetramerization\n                    of PKM2 in macrophages","volume":"13","author":"B Huang","year":"2022","journal-title":"Front Pharmacol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13020-021-00426-1","article-title":"Shikonin promotes ubiquitination and degradation of cIAP1\/2-mediated apoptosis\n                    and necrosis in triple negative breast cancer cells","volume":"16","author":"A Wang","year":"2021","journal-title":"Chin Med"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"156590","DOI":"10.1016\/j.phymed.2025.156590","article-title":"Deoxyshikonin from Arnebiae Radix promotes hair growth by targeting the\n                    Wnt\/\u03b2-catenin signaling 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Chen","year":"2011","journal-title":"Oncogene"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"3085","DOI":"10.3390\/nu17193085","article-title":"Shikonin as a dietary phytochemical with multi-target anti-cancer activities:\n                    From molecular mechanisms to translational applications","volume":"17","author":"C Y Lew","year":"2025","journal-title":"Nutrients"},{"key":"ref36","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2024.1416781","article-title":"Research progress in mechanism of anticancer action of shikonin targeting\n                    reactive oxygen species","volume":"15","author":"K Qi","year":"2024","journal-title":"Front Pharmacol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"905755","DOI":"10.3389\/fphar.2022.905755","article-title":"Review of shikonin and derivatives: isolation, chemistry, biosynthesis,\n                    pharmacology and toxicology","volume":"13","author":"S Yadav","year":"2022","journal-title":"Front 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