{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T06:32:52Z","timestamp":1792477972737,"version":"4.5.0"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T00:00:00Z","timestamp":1652140800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p>Vascular smooth muscle cell (VSMC) phenotypic transformation, proliferation, and migration play a pivotal role in developing neointimal hyperplasia after vascular injury, including percutaneous transluminal angioplasty and other cardiovascular interventions. Anemoside B4 (B4) is a unique saponin identified from the Pulsatilla chinensis (Bge.) Regel, which has known anti-inflammatory activities. However, its role in modulating VSMC functions and neointima formation has not been evaluated. Herein, we demonstrate that B4 administration had a potent therapeutic effect in reducing neointima formation in a preclinical mouse femoral artery endothelium denudation model. Bromodeoxyuridine incorporation study showed that B4 attenuated neointimal VSMC proliferation<jats:italic>in vivo<\/jats:italic>. Consistent with the<jats:italic>in vivo<\/jats:italic>findings, B4 attenuated PDGF-BB-induced mouse VSMC proliferation and migration<jats:italic>in vitro<\/jats:italic>. Moreover, quantitative RT-PCR and Western blot analysis demonstrated that B4 suppressed PDGF-BB-induced reduction of SM22\u03b1, SMA, and Calponin, suggesting that B4 inhibited the transformation of VSMCs from contractile to the synthetic phenotype. Mechanistically, our data showed B4 dose-dependently inhibited the activation of the phosphatidylinositol 3-kinase (PI3K)\/AKT and p38 mitogen-activated protein kinase MAPK signaling pathways. Subsequently, we determined that B4 attenuated VSMC proliferation and migration in a p38 MAPK and AKT dependent manner using pharmacological inhibitors. Taken together, this study identified, for the first time, Anemoside B4 as a potential therapeutic agent in regulating VSMC plasticity and combating restenosis after the vascular intervention.<\/jats:p>","DOI":"10.3389\/fcvm.2022.907490","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T07:06:32Z","timestamp":1652166392000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["Anemoside B4 Inhibits Vascular Smooth Muscle Cell Proliferation, Migration, and Neointimal Hyperplasia"],"prefix":"10.3389","volume":"9","author":[{"given":"Dan","family":"Shan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luling","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingshan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoyue","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulin","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-feng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1161\/CIRCINTERVENTIONS.110.957332","article-title":"Vascular smooth muscle cell proliferation in restenosis","volume":"4","author":"Marx","year":"2011","journal-title":"Circ Cardiovasc Interv."},{"key":"B2","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1152\/physrev.00041.2003","article-title":"Molecular regulation of vascular smooth muscle cell differentiation in development and disease","volume":"84","author":"Owens","year":"2004","journal-title":"Physiol Rev."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1161\/CIRCRESAHA.118.314187","article-title":"TEAD1 (TEA Domain Transcription Factor 1) promotes smooth muscle cell proliferation through upregulating SLC1A5 (Solute Carrier Family 1 Member 5)-mediated glutamine uptake","volume":"124","author":"Osman","year":"2019","journal-title":"Circ Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1093\/icvts\/ivy101","article-title":"Saucy. 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