{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T02:42:24Z","timestamp":1776825744944,"version":"3.51.2"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T00:00:00Z","timestamp":1480550400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81120108025"],"award-info":[{"award-number":["81120108025"]}],"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":["81473410"],"award-info":[{"award-number":["81473410"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science and Technology Project of Guangzhou City","award":["201509010004"],"award-info":[{"award-number":["201509010004"]}]},{"DOI":"10.13039\/501100003453","name":"Guangdong Natural Science Foundation","doi-asserted-by":"crossref","award":["2015A030312012"],"award-info":[{"award-number":["2015A030312012"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ethnopharmacology"],"published-print":{"date-parts":[[2016,12]]},"DOI":"10.1016\/j.jep.2016.07.021","type":"journal-article","created":{"date-parts":[[2016,7,15]],"date-time":"2016-07-15T19:07:55Z","timestamp":1468609675000},"page":"1-11","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":34,"special_numbering":"C","title":["Spica prunellae and its marker compound rosmarinic acid induced the expression of efflux transporters through activation of Nrf2-mediated signaling pathway in HepG2 cells"],"prefix":"10.1016","volume":"193","author":[{"given":"Jinjun","family":"Wu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanfeng","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangyuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guiyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rilan","family":"Ou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunli","family":"Tong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuting","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linlin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongqiu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.jep.2016.07.021_bib1","first-page":"335","article-title":"Nrf2-dependent and -independent induction of ABC transporters ABCC1, ABCC2, and ABCG2 in HepG2 cells under oxidative stress","volume":"6","author":"Adachi","year":"2007","journal-title":"J. Exp. Ther. Oncol."},{"key":"10.1016\/j.jep.2016.07.021_bib2","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.tiv.2011.01.014","article-title":"The effect of Nrf2 knockout on the constitutive expression of drug metabolizing enzymes and transporters in C57Bl\/6 mice livers","volume":"25","author":"Anwar-Mohamed","year":"2011","journal-title":"Toxicol. Vitro"},{"key":"10.1016\/j.jep.2016.07.021_bib3","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1054\/bjoc.2001.2165","article-title":"Mechanism of sensitization of MDR cancer cells by Pluronic block copolymers: selective energy depletion","volume":"85","author":"Batrakova","year":"2001","journal-title":"Br. J. Cancer"},{"key":"10.1016\/j.jep.2016.07.021_bib4","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1124\/dmd.105.009118","article-title":"Use of cryopreserved human hepatocytes in sandwich culture to measure hepatobiliary transport","volume":"34","author":"Bi","year":"2006","journal-title":"Drug Metab. Dispos."},{"key":"10.1016\/j.jep.2016.07.021_bib5","first-page":"59","article-title":"Polymorphisms in the ABC drug transporter gene MDR1","volume":"1","author":"Brinkmann","year":"2001","journal-title":"Pharm. J."},{"key":"10.1016\/j.jep.2016.07.021_bib6","doi-asserted-by":"crossref","first-page":"202","DOI":"10.3892\/ijo.2012.1703","article-title":"Ethyl acetate extraction from a Chinese herbal formula, Jiedu Xiaozheng Yin, inhibits the proliferation of hepatocellular carcinoma cells via induction of G0\/G1 phase arrest in vivo and in vitro","volume":"42","author":"Cao","year":"2013","journal-title":"Int. J. Oncol."},{"key":"10.1016\/j.jep.2016.07.021_bib7","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.3892\/or.2012.2202","article-title":"Jiedu Xiaozheng Yin, a Chinese herbal formula, inhibits tumor angiogenesis via downregulation of VEGF-A and VEGFR-2 expression in vivo and in vitro","volume":"29","author":"Cao","year":"2013","journal-title":"Oncol. Rep."},{"key":"10.1016\/j.jep.2016.07.021_bib8","doi-asserted-by":"crossref","first-page":"8477","DOI":"10.1128\/MCB.24.19.8477-8486.2004","article-title":"The Keap1-BTB protein is an adaptor that bridges Nrf2 to a Cul3-based E3 ligase: oxidative stress sensing by a Cul3-Keap1 ligase","volume":"24","author":"Cullinan","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"10.1016\/j.jep.2016.07.021_bib9","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/nrd3028","article-title":"Membrane transporters in drug development","volume":"9","author":"Giacomini","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.jep.2016.07.021_bib10","first-page":"3057","article-title":"Textual research on original plant and dietotherapy history of Prunella vulgaris","volume":"36","author":"Guo","year":"2011","journal-title":"China J. Chin. Mater. Med."},{"key":"10.1016\/j.jep.2016.07.021_bib11","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1016\/j.foodchem.2012.07.061","article-title":"Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP 3A","volume":"135","author":"Hou","year":"2012","journal-title":"Food Chem."},{"key":"10.1016\/j.jep.2016.07.021_bib12","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1016\/j.phymed.2014.06.013","article-title":"Reversal of P-glycoprotein (p-gp) mediated multidrug resistance in colon cancer cells by cryptotanshinone and dihydrotanshinone of Salvia miltiorrhiza","volume":"21","author":"Hu","year":"2014","journal-title":"Phytomedicine"},{"key":"10.1016\/j.jep.2016.07.021_bib13","first-page":"1083","article-title":"Research progress on effect and toxicology of Prunella vulgaris","volume":"29","author":"Huang","year":"2013","journal-title":"Chin. J. Public Health"},{"key":"10.1016\/j.jep.2016.07.021_bib14","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.canlet.2005.08.025","article-title":"Rosmarinic acid inhibits angiogenesis and its mechanism of action in vitro","volume":"239","author":"Huang","year":"2006","journal-title":"Cancer Lett."},{"key":"10.1016\/j.jep.2016.07.021_bib15","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1006\/bbrc.1997.6943","article-title":"An Nrf2\/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements","volume":"236","author":"Itoh","year":"1997","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.jep.2016.07.021_bib16","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/j.tiv.2015.03.013","article-title":"Regulation of the expression of renal drug transporters in KEAP1-knockdown human tubular cells","volume":"29","author":"Jeong","year":"2015","journal-title":"Toxicol. In Vitro."},{"key":"10.1016\/j.jep.2016.07.021_bib17","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s40262-013-0053-x","article-title":"Telaprevir: clinical pharmacokinetics, pharmacodynamics, and drug-drug interactions","volume":"52","author":"Kiang","year":"2013","journal-title":"Clin. Pharmacokinet."},{"key":"10.1016\/j.jep.2016.07.021_bib18","first-page":"7520","article-title":"Effects of glutathione on antioxidant response element-mediated gene expression and apoptosis elicited by sulforaphane","volume":"63","author":"Kim","year":"2003","journal-title":"Cancer Res."},{"key":"10.1016\/j.jep.2016.07.021_bib19","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.advenzreg.2006.01.007","article-title":"Nrf2-Keap1 regulation of cellular defense mechanisms against electrophiles and reactive oxygen species","volume":"46","author":"Kobayashi","year":"2006","journal-title":"Adv. Enzym. Regul."},{"key":"10.1016\/j.jep.2016.07.021_bib20","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.ejphar.2010.05.017","article-title":"Induction of CYP3A4 and MDR1 gene expression by baicalin, baicalein, chlorogenic acid, and ginsenoside Rf through constitutive androstane receptor- and pregnane X receptor-mediated pathways","volume":"640","author":"Li","year":"2010","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.jep.2016.07.021_bib21","first-page":"153","article-title":"Identification of the major chemical constituents of Prunella vulgaris L. by HPLC-ESI-MS\/MS","volume":"11","author":"Liang","year":"2013","journal-title":"Chin. Med. Mod. Distance Educ. China"},{"key":"10.1016\/j.jep.2016.07.021_bib22","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.3892\/ol.2013.1512","article-title":"Spica Prunellae extract inhibits the proliferation of human colon carcinoma cells via the regulation of the cell cycle","volume":"6","author":"Lin","year":"2013","journal-title":"Oncol. Lett."},{"key":"10.1016\/j.jep.2016.07.021_bib23","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/1472-6882-13-144","article-title":"Spica prunellae promotes cancer cell apoptosis, inhibits cell proliferation and tumor angiogenesis in a mouse model of colorectal cancer via suppression of stat3 pathway","volume":"13","author":"Lin","year":"2013","journal-title":"BMC Complement. Altern. Med."},{"key":"10.1016\/j.jep.2016.07.021_bib24","doi-asserted-by":"crossref","first-page":"242","DOI":"10.3390\/md10010242","article-title":"Fucoxanthin attenuates rifampin-induced cytochrome P450 3A4 (CYP3A4) and multiple drug resistance 1 (MDR1) gene expression through pregnane X receptor (PXR)-mediated pathways in human hepatoma HepG2 and colon adenocarcinoma LS174T cells","volume":"10","author":"Liu","year":"2012","journal-title":"Mar. Drugs"},{"key":"10.1016\/j.jep.2016.07.021_bib25","first-page":"95","article-title":"Research progress of Chinese herbal medical liangcha","volume":"18","author":"Luo","year":"2006","journal-title":"Strait Pharm. J."},{"key":"10.1016\/j.jep.2016.07.021_bib26","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1159\/000065457","article-title":"Suppressive effects of rosmarinic acid on mesangioproliferative glomerulonephritis in rats","volume":"92","author":"Makino","year":"2002","journal-title":"Nephron"},{"key":"10.1016\/j.jep.2016.07.021_bib27","first-page":"5","article-title":"Discussion of inhibitory of forsythoside A on efflux function and mechanism of P-glycoprotein in Caco-2 cell membrane","volume":"21","author":"Meng","year":"2015","journal-title":"Chin. J. Exp. Tradit. Med. Formula"},{"key":"10.1016\/j.jep.2016.07.021_bib28","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/BF02353473","article-title":"Overview of enzymes of drug metabolism","volume":"24","author":"Meyer","year":"1996","journal-title":"J. Pharmacokinet. Biopharm."},{"key":"10.1016\/j.jep.2016.07.021_bib29","first-page":"2703","article-title":"Effects of flavonoids from Glycyrrhizae Radix on function and expression of P-glycoprotein in Caco-2 cells","volume":"44","author":"Peng","year":"2013","journal-title":"Chin. Tradit. Herb. Drugs"},{"key":"10.1016\/j.jep.2016.07.021_bib30","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1007\/s11095-007-9370-9","article-title":"Structural influence of isothiocyanates on the antioxidant response element (ARE)-mediated heme oxygenase-1 (HO-1) expression","volume":"25","author":"Prawan","year":"2008","journal-title":"Pharm. Res."},{"key":"10.1016\/j.jep.2016.07.021_bib31","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1007\/s12031-009-9182-y","article-title":"Rosmarinic acid inhibits 6-OHDA-induced neurotoxicity by anti-oxidation in MES23.5 cells","volume":"39","author":"Ren","year":"2009","journal-title":"J. Mol. Neurosci."},{"key":"10.1016\/j.jep.2016.07.021_bib32","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.tox.2011.03.015","article-title":"Pregnane X receptor mediates the induction of P-glycoprotein by spironolactone in HepG2 cells","volume":"285","author":"Rigalli","year":"2011","journal-title":"Toxicology"},{"key":"10.1016\/j.jep.2016.07.021_bib33","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1124\/dmd.114.057216","article-title":"Zinc finger nuclease-mediated gene knockout results in loss of transport activity for P-glycoprotein, BCRP, and MRP2 in Caco-2 cells","volume":"43","author":"Sampson","year":"2015","journal-title":"Drug Metab. Dispos."},{"key":"10.1016\/j.jep.2016.07.021_bib34","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/bdd.759","article-title":"Pharmacodynamics of dietary phytochemical indoles I3C and DIM: Induction of Nrf2-mediated phase II drug metabolizing and antioxidant genes and synergism with isothiocyanates","volume":"32","author":"Saw","year":"2011","journal-title":"Biopharm. Drug Dispos."},{"key":"10.1016\/j.jep.2016.07.021_bib35","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1021\/jf9036062","article-title":"Dehydroglyasperin C isolated from licorice caused Nrf2-mediated induction of detoxifying enzymes","volume":"58","author":"Seo","year":"2010","journal-title":"J. Agric. Food Chem."},{"key":"10.1016\/j.jep.2016.07.021_bib36","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.ejpb.2008.08.010","article-title":"A Caco-2 cell based screening method for compounds interacting with MRP2 efflux protein","volume":"71","author":"Siissalo","year":"2009","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"10.1016\/j.jep.2016.07.021_bib37","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jep.2005.03.023","article-title":"In vitro and in vivo immunosuppressive activity of Spica Prunellae ethanol extract on the immune responses in mice","volume":"101","author":"Sun","year":"2005","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2016.07.021_bib38","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/nrd1984","article-title":"Targeting multidrug resistance in cancer","volume":"5","author":"Szakacs","year":"2006","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.jep.2016.07.021_bib39","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1006\/phrs.1999.0535","article-title":"P-glycoprotein system as a determinant of drug interactions: the case of digoxin-verapamil","volume":"40","author":"Verschraagen","year":"1999","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.jep.2016.07.021_bib40","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1042\/BJ20051518","article-title":"Role of Nrf2 in the regulation of the Mrp2 (ABCC2) gene","volume":"395","author":"Vollrath","year":"2006","journal-title":"Biochem. J."},{"key":"10.1016\/j.jep.2016.07.021_bib41","doi-asserted-by":"crossref","first-page":"8585","DOI":"10.1523\/JNEUROSCI.2935-13.2014","article-title":"Nrf2 upregulates ATP binding cassette transporter expression and activity at the blood-brain and blood-spinal cord barriers","volume":"34","author":"Wang","year":"2014","journal-title":"J. Neurosci."},{"key":"10.1016\/j.jep.2016.07.021_bib42","doi-asserted-by":"crossref","first-page":"734867","DOI":"10.1155\/2014\/734867","article-title":"Coadministration of Pinellia ternata can significantly reduce Aconitum carmichaelii to inhibit CYP3A activity in rats","volume":"2014","author":"Wu","year":"2014","journal-title":"Evid.-based Complement. Altern. Med."},{"key":"10.1016\/j.jep.2016.07.021_bib43","doi-asserted-by":"crossref","first-page":"688","DOI":"10.2174\/1389200211314060005","article-title":"Pharmacogenetics, pharmacogenomics and epigenetics of Nrf2-regulated xenobiotic-metabolizing enzymes and transporters by dietary phytochemical and cancer chemoprevention","volume":"14","author":"Wu","year":"2013","journal-title":"Curr. Drug Metab."},{"key":"10.1016\/j.jep.2016.07.021_bib44","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1158\/1535-7163.MCT-10-0874","article-title":"Novel acrylonitrile derivatives, YHO-13177 and YHO-13351, reverse BCRP\/ABCG2-mediated drug resistance in vitro and in vivo","volume":"10","author":"Yamazaki","year":"2011","journal-title":"Mol. Cancer Ther."},{"key":"10.1016\/j.jep.2016.07.021_bib45","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2016.01.031","article-title":"Regulation of drug-metabolizing enzymes and efflux transporters by Astragali radix decoction and its main bioactive compounds: Implication for clinical drug-drug interactions","author":"Zhang","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2016.07.021_bib46","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1080\/00498250701867889","article-title":"Structure, function and regulation of P-glycoprotein and its clinical relevance in drug disposition","volume":"38","author":"Zhou","year":"2008","journal-title":"Xenobiotica"}],"container-title":["Journal of Ethnopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378874116304470?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378874116304470?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2019,9,11]],"date-time":"2019-09-11T02:47:39Z","timestamp":1568170059000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0378874116304470"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12]]},"references-count":46,"alternative-id":["S0378874116304470"],"URL":"https:\/\/doi.org\/10.1016\/j.jep.2016.07.021","relation":{},"ISSN":["0378-8741"],"issn-type":[{"value":"0378-8741","type":"print"}],"subject":[],"published":{"date-parts":[[2016,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Spica prunellae and its marker compound rosmarinic acid induced the expression of efflux transporters through activation of Nrf2-mediated signaling pathway in HepG2 cells","name":"articletitle","label":"Article Title"},{"value":"Journal of Ethnopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jep.2016.07.021","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2016 Elsevier Ireland Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}