{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:46:12Z","timestamp":1788871572796,"version":"build-2803163510"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2014,10,1]],"date-time":"2014-10-01T00:00:00Z","timestamp":1412121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Doctor Scientific Research Foundation in Guangdong Medical College","award":["10201B01202"],"award-info":[{"award-number":["10201B01202"]}]},{"name":"Doctor Scientific Research Foundation in Guangdong Medical College","award":["XB1322"],"award-info":[{"award-number":["XB1322"]}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["S2013040012115"],"award-info":[{"award-number":["S2013040012115"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81270212"],"award-info":[{"award-number":["81270212"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81300035"],"award-info":[{"award-number":["81300035"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Baicalin, a natural flavone, has antithrombotic, antihyperlipidemic and antiinflammortory activity. It can also inhibit cancer cell proliferation and reduce brain cell apoptosis. This study aimed to elucidate the effect of baicalin on the excessive proliferation of human pulmonary arterial smooth muscle cells (HPASMCs) induced by transforming growth factor-\u03b21 (TGF-\u03b21) and to investigate the roles of hypoxia inducible factor-1\u03b1 (HIF-1\u03b1) and aryl hydrocarbon receptor (AhR) in mediating this TGF-\u03b21-induced excessive proliferation of HPASMCs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>TGF-\u03b21-induced proliferation of HPASMCs was assayed using the CCK8 method. The cellular phenotype was identified by immunocytochemical staining. Expression of HIF-1\u03b1 and AhR mRNA was determined by real-time quantitative PCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key findings<\/jats:title>\n                    <jats:p>TGF-\u03b21 promoted significantly HPASMC proliferation (P &amp;lt; 0.05) and induced a phenotypic switch from the contractile to synthetic type. Baicalin inhibited this TGF-\u03b21-induced phenotypic switch and consequently the excessive growth of HPASMCs in a time-dependent and dose-dependent manner (P &amp;lt; 0.05). Furthermore, baicalin attenuated the abnormal proliferation of HPASMCs through suppression of the HIF-1\u03b1 and AhR pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study shows that baicalin has the potential to be used as a novel drug in the treatment of pulmonary arterial hypertension pathology by antagonizing HIF-1\u03b1 and AhR expression and subsequently decreasing HPASMC proliferation and the phenotypic switch.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jphp.12273","type":"journal-article","created":{"date-parts":[[2014,5,18]],"date-time":"2014-05-18T23:36:44Z","timestamp":1400456204000},"page":"1469-1477","source":"Crossref","is-referenced-by-count":46,"title":["Baicalin attenuates transforming growth factor-\u03b21-induced human pulmonary artery smooth muscle cell proliferation and phenotypic switch by inhibiting hypoxia inducible factor-1\u03b1 and aryl hydrocarbon receptor expression"],"prefix":"10.1093","volume":"66","author":[{"given":"Shian","family":"Huang","sequence":"first","affiliation":[{"name":"Laboratory of Cardiovascular Remodeling and Pharmaceutical Biotechnology, Department of Cardiovascular, The Affiliated Hospital, Guangdong Medical College , Zhanjiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puwen","family":"Chen","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Remodeling and Pharmaceutical Biotechnology, Department of Cardiovascular, The Affiliated Hospital, Guangdong Medical College , Zhanjiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaorong","family":"Shui","sequence":"additional","affiliation":[{"name":"Vascular Surgery Laboratory, The Affiliated Hospital, Guangdong Medical College , Zhanjiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"He","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Remodeling and Pharmaceutical Biotechnology, Department of Cardiovascular, The Affiliated Hospital, Guangdong Medical College , Zhanjiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heyong","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Pulmonary Hospital, Tongji University School of Medicine , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zheng","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Remodeling and Pharmaceutical Biotechnology, Department of Cardiovascular, The Affiliated Hospital, Guangdong Medical College , Zhanjiang,","place":["China"]},{"name":"Department of Obstetrics and Gynecology, University of Wisconsin\u2013Madison , Madison, WI,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Remodeling and Pharmaceutical Biotechnology, Department of Cardiovascular, The Affiliated Hospital, Guangdong Medical College , Zhanjiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianwen","family":"Li","sequence":"additional","affiliation":[{"name":"Vascular Surgery Laboratory, The Affiliated Hospital, Guangdong Medical College , Zhanjiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqiang","family":"Xue","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Remodeling and Pharmaceutical Biotechnology, Department of Cardiovascular, The Affiliated Hospital, Guangdong Medical College , Zhanjiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Chen","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Remodeling and Pharmaceutical Biotechnology, Department of Cardiovascular, The Affiliated Hospital, Guangdong Medical College , Zhanjiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Lei","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Remodeling and Pharmaceutical Biotechnology, Department of Cardiovascular, The Affiliated Hospital, Guangdong Medical College , Zhanjiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,10,1]]},"reference":[{"key":"2024103109164137400_jphp12273-cit-0001","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1164\/rccm.201207-1290OC","article-title":"Lower socioeconomic status is associated with worse outcomes in pulmonary arterial hypertension","volume":"187","author":"Wu","year":"2013","journal-title":"Am J Respir Crit Care Med"},{"key":"2024103109164137400_jphp12273-cit-0002","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3006674","article-title":"Blocking macrophage leukotriene b4 prevents endothelial injury and reverses pulmonary hypertension","volume":"5","author":"Tian","year":"2013","journal-title":"Sci Transl Med"},{"key":"2024103109164137400_jphp12273-cit-0003","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1042\/BJ20121344","article-title":"PDGF-mediated autophagy regulates vascular smooth muscle cell phenotype and resistance to oxidative stress","volume":"451","author":"Salabei","year":"2013","journal-title":"Biochem J"},{"key":"2024103109164137400_jphp12273-cit-0004","doi-asserted-by":"crossref","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":"2024103109164137400_jphp12273-cit-0005","doi-asserted-by":"crossref","first-page":"C1541","DOI":"10.1152\/ajpcell.00068.2010","article-title":"Hypoxic upregulation of arginase II in human lung endothelial cells","volume":"299","author":"Krotova","year":"2010","journal-title":"Am J Physiol Cell Physiol"},{"key":"2024103109164137400_jphp12273-cit-0006","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1007\/s00277-010-0954-9","article-title":"Arginase levels and their association with Th17-related cytokines, soluble adhesion molecules (sICAM-1 and sVCAM-1) and hemolysis markers among steady-state sickle cell anemia patients","volume":"89","author":"Vilas-Boas","year":"2010","journal-title":"Ann Hematol"},{"key":"2024103109164137400_jphp12273-cit-0007","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1291\/hypres.25.911","article-title":"Transforming growth factor-beta expression in cardiovascular organs in stroke-prone spontaneously hypertensive rats with the development of hypertension","volume":"25","author":"Tahira","year":"2002","journal-title":"Hypertens Res"},{"key":"2024103109164137400_jphp12273-cit-0008","doi-asserted-by":"crossref","first-page":"L717","DOI":"10.1152\/ajplung.00070.2002","article-title":"Effect of bradykinin, TGF-beta1, IL-1beta, and hypoxia on COX-2 expression in pulmonary artery smooth muscle cells","volume":"283","author":"Bradbury","year":"2002","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2024103109164137400_jphp12273-cit-0009","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1006\/bbrc.1998.8543","article-title":"Hypoxia regulates expression of the endothelin-1 gene through a proximal hypoxia-inducible factor-1 binding site on the antisense strand","volume":"245","author":"Hu","year":"1998","journal-title":"Biochem Biophys Res Commun"},{"key":"2024103109164137400_jphp12273-cit-0010","doi-asserted-by":"crossref","first-page":"2585","DOI":"10.1161\/01.ATV.0000250932.24151.50","article-title":"Coupling eNOS uncoupling to the innate immune response","volume":"26","author":"Rabelink","year":"2006","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2024103109164137400_jphp12273-cit-0011","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1093\/cvr\/cvq152","article-title":"HIF-1 inhibition decreases systemic vascular remodelling diseases by promoting apoptosis through a hexokinase 2-dependent mechanism","volume":"88","author":"Lambert","year":"2010","journal-title":"Cardiovasc Res"},{"key":"2024103109164137400_jphp12273-cit-0012","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1093\/oxfordjournals.jbchem.a003289","article-title":"Overexpression of the aryl hydrocarbon receptor (AhR) accelerates the cell proliferation of A549 cells","volume":"132","author":"Shimba","year":"2002","journal-title":"J Biochem"},{"key":"2024103109164137400_jphp12273-cit-0013","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/S0939-4753(03)80026-1","article-title":"The aryl hydrocarbon receptor and its xenobiotic ligands: a fundamental trigger for cardiovascular diseases","volume":"13","author":"Savouret","year":"2003","journal-title":"Nutr Metab Cardiovasc Dis"},{"key":"2024103109164137400_jphp12273-cit-0014","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1111\/exd.12148","article-title":"Role of the aryl hydrocarbon receptor in tobacco smoke extract-induced matrix metalloproteinase-1 expression","volume":"22","author":"Ono","year":"2013","journal-title":"Exp Dermatol"},{"key":"2024103109164137400_jphp12273-cit-0015","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1124\/mol.107.040204","article-title":"Repression of aryl hydrocarbon receptor (AHR) signaling by AHR repressor: role of DNA binding and competition for AHR nuclear translocator","volume":"73","author":"Evans","year":"2008","journal-title":"Mol Pharmacol"},{"key":"2024103109164137400_jphp12273-cit-0016","first-page":"282","article-title":"Pharmacopoeia of the People's Republic of China, the First Division","author":"China Pharmacopoeia Committee","year":"1999","edition":"2010 edn"},{"key":"2024103109164137400_jphp12273-cit-0017","doi-asserted-by":"crossref","first-page":"177","DOI":"10.2174\/1568006043586206","article-title":"Biological properties of baicalein in cardiovascular system","volume":"5","author":"Huang","year":"2005","journal-title":"Curr Drug Targets Cardiovasc Haematol Disord"},{"key":"2024103109164137400_jphp12273-cit-0018","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1271\/bbb.50698","article-title":"Antioxidative and anti-inflammatory activities of polyhydroxyflavonoids of Scutellaria baicalensis GEORGI","volume":"70","author":"Huang","year":"2006","journal-title":"Biosci Biotechnol Biochem"},{"key":"2024103109164137400_jphp12273-cit-0019","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/S0090-4295(01)01239-0","article-title":"In vitro mechanism of PC SPES","volume":"58","author":"Chenn","year":"2001","journal-title":"Urology"},{"key":"2024103109164137400_jphp12273-cit-0020","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.ejphar.2009.12.014","article-title":"Baicalin suppresses lung carcinoma and lung metastasis by SOD mimic and HIF-1alpha inhibition","volume":"630","author":"Du","year":"2010","journal-title":"Eur J Pharmacol"},{"key":"2024103109164137400_jphp12273-cit-0021","first-page":"1505","article-title":"The influences of baicalin on hypoxia-inducible factor-1\u03b1 gene expression following hypoxic-ischemic brain damage in neonatal rat","volume":"21","author":"Zheng","year":"2004","journal-title":"Chin J Exp Surg"},{"key":"2024103109164137400_jphp12273-cit-0022","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1248\/bpb.31.838","article-title":"Blockade of the dioxin pathway by herbal medicine Formula Bupleuri Minor: identification of active entities for suppression of AhR activation","volume":"31","author":"Kasai","year":"2008","journal-title":"Biol Pharm Bull"},{"key":"2024103109164137400_jphp12273-cit-0023","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1093\/abbs\/gmq129","article-title":"Texture analysis of liver fibrosis microscopic images: a study on the effect of biomarkers","volume":"43","author":"Amin","year":"2011","journal-title":"Acta Biochim Biophys Sin (Shanghai)"},{"key":"2024103109164137400_jphp12273-cit-0024","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1177\/2040622311420773","article-title":"Treating pulmonary arterial hypertension: current treatments and future prospects","volume":"2","author":"Raja","year":"2011","journal-title":"Ther Adv Chronic Dis"},{"key":"2024103109164137400_jphp12273-cit-0025","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.pupt.2011.09.003","article-title":"YC-1 attenuates hypoxia-induced pulmonary arterial hypertension in mice","volume":"24","author":"Huh","year":"2011","journal-title":"Pulm Pharmacol Ther"},{"key":"2024103109164137400_jphp12273-cit-0026","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1055\/s-0033-1350621","article-title":"Eupatilin, a major flavonoid of Artemisia, attenuates aortic smooth muscle cell proliferation and migration by inhibiting PI3K, MKK3\/6, and MKK4 activities","volume":"79","author":"Son","year":"2013","journal-title":"Planta Med"},{"key":"2024103109164137400_jphp12273-cit-0027","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1142\/S0192415X1100910X","article-title":"Botanical flavonoids on coronary heart disease","volume":"39","author":"Wang","year":"2011","journal-title":"Am J Chin Med"},{"key":"2024103109164137400_jphp12273-cit-0028","doi-asserted-by":"crossref","first-page":"e74826","DOI":"10.1371\/journal.pone.0074826","article-title":"Genipin inhibits TNF-\u03b1-induced vascular smooth muscle cell proliferation and migration via induction of HO-1","volume":"8","author":"Jiang","year":"2013","journal-title":"PLoS ONE"},{"key":"2024103109164137400_jphp12273-cit-0029","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1271\/bbb.120800","article-title":"Identification of a nitric oxide generation-stimulative principle in Scutellariae radix","volume":"77","author":"Chen","year":"2013","journal-title":"Biosci Biotechnol Biochem"},{"key":"2024103109164137400_jphp12273-cit-0030","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1038\/nrc1189","article-title":"Cancer chemoprevention with dietary phytochemicals","volume":"3","author":"Surh","year":"2003","journal-title":"Nat Rev Cancer"},{"key":"2024103109164137400_jphp12273-cit-0031","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/nrc3017","article-title":"Molecular targets of phytochemicals for cancer prevention","volume":"11","author":"Lee","year":"2011","journal-title":"Nat Rev Cancer"},{"key":"2024103109164137400_jphp12273-cit-0032","first-page":"1123","article-title":"Mechanism of action and development of selective aryl hydrocarbon receptor modulators for treatment of hormone-dependent cancers","volume":"20","author":"Safe","year":"2002","journal-title":"Int J Oncol"},{"key":"2024103109164137400_jphp12273-cit-0033","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.ctrv.2006.05.003","article-title":"Oncological implications of hypoxia inducible factor-1alpha (HIF-1alpha) expression","volume":"32","author":"O'Donnell","year":"2006","journal-title":"Cancer Treat Rev"},{"key":"2024103109164137400_jphp12273-cit-0034","doi-asserted-by":"crossref","first-page":"483","DOI":"10.4103\/2045-8932.105037","article-title":"Peroxisome proliferator-activated receptor gamma (PPAR\u03b3) regulates thrombospondin-1 and Nox4 expression in hypoxia-induced human pulmonary artery smooth muscle cell proliferation","volume":"2","author":"Green","year":"2012","journal-title":"Pulm Circ"},{"key":"2024103109164137400_jphp12273-cit-0035","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.bbrc.2011.06.018","article-title":"AhR deficiency impairs expression of LPS-induced inflammatory genes in mice","volume":"410","author":"Wu","year":"2011","journal-title":"Biochem Biophys Res Commun"},{"key":"2024103109164137400_jphp12273-cit-0036","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1093\/toxsci\/kfs024","article-title":"Aryl hydrocarbon receptor (AhR) regulates silica-induced inflammation but not fibrosis","volume":"126","author":"Beamer","year":"2012","journal-title":"Toxicol Sci"},{"key":"2024103109164137400_jphp12273-cit-0037","doi-asserted-by":"crossref","first-page":"184","DOI":"10.2174\/187152711794480384","article-title":"Flavones from root of Scutellaria baicalensis Georgi: drugs of the future in neurodegeneration?","volume":"10","author":"Gasiorowski","year":"2011","journal-title":"CNS Neurol Disord Drug Targets"},{"key":"2024103109164137400_jphp12273-cit-0038","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/j.1749-6632.2009.05125.x","article-title":"Dioxin and immune regulation: emerging role of aryl hydrocarbon receptor in the generation of regulatory T cells","volume":"1183","author":"Marshall","year":"2010","journal-title":"Ann N Y Acad Sci"},{"key":"2024103109164137400_jphp12273-cit-0039","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nature06881","article-title":"The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins","volume":"453","author":"Veldhoen","year":"2008","journal-title":"Nature"},{"key":"2024103109164137400_jphp12273-cit-0040","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.taap.2010.03.013","article-title":"Functional and phenotypic effects of AhR activation in inflammatory dendritic cells","volume":"246","author":"Bankoti","year":"2010","journal-title":"Toxicol Appl Pharmacol"}],"container-title":["Journal of Pharmacy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjphp.12273","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjphp.12273","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/66\/10\/1469\/60252808\/jphp12273.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/66\/10\/1469\/60252808\/jphp12273.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T05:24:42Z","timestamp":1730352282000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpp\/article\/66\/10\/1469\/6128030"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10,1]]},"references-count":40,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2014,10,1]]},"published-print":{"date-parts":[[2014,10,1]]}},"URL":"https:\/\/doi.org\/10.1111\/jphp.12273","relation":{},"ISSN":["2042-7158","0022-3573"],"issn-type":[{"value":"2042-7158","type":"electronic"},{"value":"0022-3573","type":"print"}],"subject":[],"published-other":{"date-parts":[[2014,10]]},"published":{"date-parts":[[2014,10,1]]}}}