{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:03:19Z","timestamp":1792008199725,"version":"4.4.0"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,2,1]],"date-time":"2014-02-01T00:00:00Z","timestamp":1391212800000},"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":"crossref","award":["81374040"],"award-info":[{"award-number":["81374040"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81301447"],"award-info":[{"award-number":["81301447"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31170852"],"award-info":[{"award-number":["31170852"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81001322"],"award-info":[{"award-number":["81001322"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Oral submucous fibrosis (<jats:styled-content style=\"fixed-case\">OSF<\/jats:styled-content>) is a premalignant and fibrosing disease, which is closely associated with the habit of chewing areca\u00a0nut. <jats:italic>Panax notoginseng<\/jats:italic> Buck F. H. Chen is an often used antifibrotic and antitumor agent. To treat areca\u00a0nut\u2010induced <jats:styled-content style=\"fixed-case\">OSF<\/jats:styled-content>, we have developed a chewable tablet, in which one of the major medicines is total <jats:italic>Panax notoginseng<\/jats:italic> saponins (<jats:styled-content style=\"fixed-case\">PNS<\/jats:styled-content>). In this study, we have investigated the antifibrotic effect and mechanism of <jats:styled-content style=\"fixed-case\">PNS<\/jats:styled-content> on areca\u00a0nut\u2010induced <jats:styled-content style=\"fixed-case\">OSF <\/jats:styled-content><jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Through human procollagen gene promoter luciferase reporter plasmid, hydroxyproline assay, gelatin zymography, <jats:styled-content style=\"fixed-case\">qRT<\/jats:styled-content>\u2010PCR, ELISA, and Western blot, the influences of PNS on areca nut extract (ANE)\u2010induced cell growth, collagen accumulation, procollagen gene transcription, MMP\u20102\/\u20109 activity, MMP\u20101\/\u201013 and TIMP\u20101\/\u20102 expression, cytokine secretion, and the activation of PI3K\/AKT, ERK\/JNK\/p38 MAPK, and TGF\u03b2\/Smads pathways were detected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>Panax notoginseng<\/jats:italic> saponins could inhibit the <jats:styled-content style=\"fixed-case\">ANE<\/jats:styled-content>\u2010induced abnormal growth and collagen accumulation of oral mucosal fibroblasts in a concentration\u2010dependent manner. <jats:styled-content style=\"fixed-case\">PNS<\/jats:styled-content> (25\u00a0\u03bcg\/ml) could significantly inhibit the <jats:styled-content style=\"fixed-case\">ANE<\/jats:styled-content>\u2010induced expression of Col1A1 and Col3A1, augment the <jats:styled-content style=\"fixed-case\">ANE<\/jats:styled-content>\u2010induced decrease of <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u20102\/\u20109 activity, inhibit the <jats:styled-content style=\"fixed-case\">ANE<\/jats:styled-content>\u2010induced increase of <jats:styled-content style=\"fixed-case\">TIMP<\/jats:styled-content>\u20101\/\u20102 expression, and decrease the <jats:styled-content style=\"fixed-case\">ANE<\/jats:styled-content>\u2010induced transcription and release of <jats:styled-content style=\"fixed-case\">CTGF<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> TGF<\/jats:styled-content>\u03b21, <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106, and <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u03b1. <jats:styled-content style=\"fixed-case\">PNS<\/jats:styled-content> (25\u00a0\u03bcg\/ml) also significantly inhibited the <jats:styled-content style=\"fixed-case\">ANE<\/jats:styled-content>\u2010induced activation of <jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">JNK<\/jats:styled-content>\/p38 <jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content> pathways in oral mucosal fibroblasts and the <jats:styled-content style=\"fixed-case\">ANE<\/jats:styled-content>\u2010induced activation of <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u03b2\/smad pathway in HaCaT cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>Panax notoginseng<\/jats:italic> saponins possess excellent anti\u2010<jats:styled-content style=\"fixed-case\">OSF<\/jats:styled-content> activity, and its mechanism may be related to its ability to inhibit the <jats:styled-content style=\"fixed-case\">ANE<\/jats:styled-content>\u2010induced activation of <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K\/<jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> ERK<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">JNK<\/jats:styled-content>\/p38 <jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content>, and <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u03b2\/smad pathways.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jop.12158","type":"journal-article","created":{"date-parts":[[2014,2,1]],"date-time":"2014-02-01T06:47:15Z","timestamp":1391237235000},"page":"464-470","source":"Crossref","is-referenced-by-count":19,"title":["<i>Panax notoginseng<\/i> saponins inhibit areca nut extract\u2010induced oral submucous fibrosis <i>in vitro<\/i>"],"prefix":"10.1111","volume":"43","author":[{"given":"Jian\u2010Ping","family":"Dai","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology Shantou University Medical College Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Xuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Shantou University Medical College Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan\u2010Xia","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Shantou University Medical College Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian\u2010Ying","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Shantou University Medical College Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Shantou University Medical College Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge\u2010Fei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Shantou University Medical College Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Zhong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine University of Maryland College Park MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang\u2010Sheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Shantou University Medical College Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,2]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.567"},{"key":"e_1_2_5_3_1","first-page":"121","article-title":"Induction of apoptosis in human lung carcinoma cells by the water extract of Panax notoginseng is associated with the activation of caspase\u20103 through downregulation of Akt","volume":"35","author":"Park SC","year":"2009","journal-title":"Int J Oncol"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.07.099"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000315061"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2011.05.010"},{"key":"e_1_2_5_7_1","first-page":"1443","article-title":"Effects of Panax notoginseng flower extract on the TGF\u2010beta\/Smad signal transduction pathway in heart remodeling of human chymase transgenic mice","volume":"5","author":"Wang Y","year":"2012","journal-title":"Mol Med Rep"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.2008.00659.x"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.2008.00695.x"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.2010.00998.x"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2006.08.003"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M404465200"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0051806"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/154405910808701111"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.2008.00738.x"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/1087057111435236"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00759-13"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042706"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0061026"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1368-8375(01)00045-8"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2008.01185.x"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.21.022404.142018"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00966.2011"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.076505"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2013.06.028"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2007.04.005"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2008.11.020"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2010.02.022"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2005.12.002"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0b013e3181ceede4"}],"container-title":["Journal of Oral Pathology &amp; Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjop.12158","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjop.12158","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jop.12158","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T09:14:17Z","timestamp":1696238057000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jop.12158"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,2]]},"references-count":29,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2014,7]]}},"alternative-id":["10.1111\/jop.12158"],"URL":"https:\/\/doi.org\/10.1111\/jop.12158","archive":["Portico"],"relation":{},"ISSN":["0904-2512","1600-0714"],"issn-type":[{"value":"0904-2512","type":"print"},{"value":"1600-0714","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,2]]}}}