{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T03:23:01Z","timestamp":1771125781200,"version":"3.50.1"},"reference-count":53,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"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":"crossref","award":["81073098"],"award-info":[{"award-number":["81073098"]}],"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":["81374012"],"award-info":[{"award-number":["81374012"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Academic and Technique Foregoer Foundation of Anhui province, China","award":["2012381"],"award-info":[{"award-number":["2012381"]}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ethnopharmacology"],"published-print":{"date-parts":[[2014,1]]},"DOI":"10.1016\/j.jep.2013.10.022","type":"journal-article","created":{"date-parts":[[2013,11,15]],"date-time":"2013-11-15T19:12:00Z","timestamp":1384542720000},"page":"198-209","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":33,"title":["Compound Astragalus and Salvia miltiorrhiza extract suppresses hepatocellular carcinoma progression by inhibiting fibrosis and PAI-1 mRNA transcription"],"prefix":"10.1016","volume":"151","author":[{"given":"Wenjuan","family":"Rui","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shufang","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoxiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linjie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.jep.2013.10.022_bib1","first-page":"879","article-title":"Expression of retinoid X receptor alpha is decreased in 3\u2032-methyl-4-dimethylaminoazobenzene-induced hepatocellular carcinoma in rats","volume":"18","author":"Ando","year":"2007","journal-title":"Oncol. Rep."},{"key":"10.1016\/j.jep.2013.10.022_bib2","first-page":"189","article-title":"Astragalus saponins induce apoptosis via an ERK-independent NF-\u03baB signaling pathway in the human hepatocellular HepG2 cell line","volume":"23","author":"Auyeung","year":"2009","journal-title":"Int. J. Mol. Med."},{"key":"10.1016\/j.jep.2013.10.022_bib3","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.dld.2008.02.007","article-title":"Effect of gonadectomy on HCC development in HBV transgenic mice","volume":"41","author":"Barone","year":"2009","journal-title":"Dig. Liver Dis."},{"key":"10.1016\/j.jep.2013.10.022_bib4","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1002\/ptr.1938","article-title":"The effect of Echinacea purpurea Astragalus membranaceus and Glycyrrhiza glabra on CD69 expression and immune cell activation in humans","volume":"20","author":"Brush","year":"2006","journal-title":"Phytother. Res."},{"key":"10.1016\/j.jep.2013.10.022_bib5","doi-asserted-by":"crossref","first-page":"285","DOI":"10.3892\/etm.2011.406","article-title":"Characterization of diethylnitrosamine-induced liver carcinogenesis in Syrian golden hamsters","volume":"3","author":"Chen","year":"2012","journal-title":"Exp. Ther. Med."},{"key":"10.1016\/j.jep.2013.10.022_bib6","first-page":"342","article-title":"Efficacy observation of compound sophora flavescens injection combined with Lamivudine on chronic hepatitis B cirrhosis","volume":"24","author":"Chen","year":"2013","journal-title":"Chin. Pharm."},{"key":"10.1016\/j.jep.2013.10.022_bib7","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.canlet.2006.12.001","article-title":"In vitro and in vivo anti-tumor effects of Astragalus membranaceus","volume":"252","author":"Cho","year":"2007","journal-title":"Cancer Lett."},{"key":"10.1016\/j.jep.2013.10.022_bib8","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1093\/carcin\/21.2.331","article-title":"Curcumin-containing diet inhibits diethylnitrosamine-induced murine hepatocarcinogenesis","volume":"21","author":"Chuang","year":"2000","journal-title":"Carcinogenesis"},{"key":"10.1016\/j.jep.2013.10.022_bib9","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.jhep.2009.10.035","article-title":"The hepatitis C virus core protein indirectly induces alpha-smooth muscle actin expression in hepatic stellate cells via interleukin-8","volume":"52","author":"Cl\u00e9ment","year":"2010","journal-title":"J. Hepatol."},{"key":"10.1016\/j.jep.2013.10.022_bib10","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s00280-002-0532-5","article-title":"Suppressive effect of Astragalus membranaceus Bunge on chemical hepatocarcinogenesis in rats","volume":"51","author":"Cui","year":"2003","journal-title":"Cancer Chemother. Pharmacol."},{"key":"10.1016\/j.jep.2013.10.022_bib11","first-page":"13","article-title":"The clinic research of huangqi injection combined with transcatheter arterial chemoembolization to treat primary hepatocellular carcinoma","volume":"27","author":"Du","year":"2008","journal-title":"Gansu Med. J."},{"key":"10.1016\/j.jep.2013.10.022_bib12","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1053\/j.gastro.2011.09.002","article-title":"Alcoholic liver disease: pathogenesis and new therapeutic targets","volume":"141","author":"Gao","year":"2011","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jep.2013.10.022_bib13","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.thromres.2009.11.034","article-title":"Plasminogen activator inhibitor-1 is an aggregate response factor with pleiotropic effects on cell signaling in vascular disease and the tumor microenvironment","volume":"125","author":"Gramling","year":"2010","journal-title":"Thromb. Res."},{"key":"10.1016\/j.jep.2013.10.022_bib14","first-page":"50","article-title":"Acute and chronic toxicity studies of Huangqi injection in mice and rats","volume":"23","author":"Han","year":"2004","journal-title":"Chin. Wild Plant Resour."},{"key":"10.1016\/j.jep.2013.10.022_bib15","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1111\/j.1365-2133.2009.09511.x","article-title":"Mechanisms of transforming growth factor\u03b21\/Smad signalling mediated by mitogen-activated protein kinase pathways in keloid fibroblasts","volume":"162","author":"He","year":"2010","journal-title":"Br. J. Dermatol."},{"key":"10.1016\/j.jep.2013.10.022_bib16","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1111\/j.1365-2133.2011.10674.x","article-title":"Compound Astragalus and Salvia miltiorrhiza extract inhibits cell proliferation, invasion and collagen synthesis in keloid fibroblasts by mediating TGF-beta\/Smad pathway","volume":"166","author":"He","year":"2012","journal-title":"Br. J. Dermatol."},{"key":"10.1016\/j.jep.2013.10.022_bib17","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1111\/j.1745-7254.2007.00606.x","article-title":"Antitumor effects of Chi-Shen extract from Salvia miltiorrhiza and Paeoniae radix on human hepatocellular carcinoma cells","volume":"28","author":"Hu","year":"2007","journal-title":"Acta Pharmacol. Sin."},{"key":"10.1016\/j.jep.2013.10.022_bib18","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1111\/j.2042-7158.2012.01549.x","article-title":"Reversal of p-glycoprotein-mediated multidrug resistance of human hepatic cancer cells by Astragaloside II","volume":"64","author":"Huang","year":"2012","journal-title":"J. Pharm. Pharmacol."},{"key":"10.1016\/j.jep.2013.10.022_bib19","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s11010-011-1043-7","article-title":"Potential preventive effect of carvacrol against diethylnitrosamine-induced hepatocellular carcinoma in rats","volume":"360","author":"Jayakumar","year":"2012","journal-title":"Mol. Cell Biochem."},{"key":"10.1016\/j.jep.2013.10.022_bib20","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1093\/carcin\/bgh093","article-title":"An acyclic retinoid, NIK-333, inhibits N-diethylnitrosamine-induced rat hepatocarcinogenesis through suppression of TGF-alpha expression and cell proliferation","volume":"25","author":"Kagawa","year":"2004","journal-title":"Carcinogenesis"},{"key":"10.1016\/j.jep.2013.10.022_bib21","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1248\/bpb.27.1946","article-title":"Immunomodulatory effect of Astragali Radix extract on murine TH1\/TH2 cell lineage development","volume":"27","author":"Kang","year":"2004","journal-title":"Biol. Pharm. Bull."},{"key":"10.1016\/j.jep.2013.10.022_bib22","doi-asserted-by":"crossref","first-page":"e41964","DOI":"10.1371\/journal.pone.0041964","article-title":"Prospective validation of ELF test in comparison with fibroscan and fibrotest to predict liver fibrosis in Asian subjects with chronic hepatitis B.","volume":"7","author":"Kim","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.jep.2013.10.022_bib23","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1002\/hep.20767","article-title":"Intrahepatic gene expression profiles and alpha-smooth muscle actin patterns in hepatitis C virus induced fibrosis","volume":"42","author":"Lau","year":"2005","journal-title":"Hepatology"},{"key":"10.1016\/j.jep.2013.10.022_bib24","first-page":"786","article-title":"Inhibiting effect of Astragalus polysaccharides on the functions of CD4+CD25 highTreg cells in the tumor microenvironment of human hepatocellular carcinoma","volume":"125","author":"Li","year":"2012","journal-title":"Chin. Med. J."},{"key":"10.1016\/j.jep.2013.10.022_bib25","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.jss.2009.10.028","article-title":"Lipid peroxidation in acute respiratory distress syndrome and liver failure","volume":"168","author":"Lichtenstern","year":"2011","journal-title":"J. Surg. Res."},{"key":"10.1016\/j.jep.2013.10.022_bib26","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.jep.2005.10.021","article-title":"In vitro protective effects of salvianolic acid B on primary hepatocytes and hepatic stellate cells","volume":"105","author":"Lin","year":"2006","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2013.10.022_bib27","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0304-3835(00)00391-8","article-title":"Salvia miltiorrhiza inhibits cell growth and induces apoptosis in human hepatoma HepG2 cells","volume":"153","author":"Liu","year":"2000","journal-title":"Cancer Lett."},{"key":"10.1016\/j.jep.2013.10.022_bib28","first-page":"553","article-title":"Research on tolerance of salvianolic acid capsule in phase I clinical trial","volume":"25","author":"Liu","year":"2004","journal-title":"Shanghai Med. Pharm. J."},{"key":"10.1016\/j.jep.2013.10.022_bib29","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1111\/j.1440-1746.2009.05981.x","article-title":"Compound Astragalus and Salvia miltiorrhiza extract inhibits cell invasion by modulating transforming growth factor-beta\/Smad in HepG2 cell","volume":"25","author":"Liu","year":"2010","journal-title":"J. Gastroenterol. Hepatol."},{"key":"10.1016\/j.jep.2013.10.022_bib30","first-page":"1429","article-title":"The protective effects of fish oil and artichoke on hepatocellular carcinoma in rats","volume":"15","author":"Metwally","year":"2011","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"10.1016\/j.jep.2013.10.022_bib31","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1093\/toxsci\/kfn174","article-title":"Role of Nrf2 and oxidative stress on fenofibrate-induced hepatocarcinogenesis in rats","volume":"106","author":"Nishimura","year":"2008","journal-title":"Toxicol. Sci."},{"key":"10.1016\/j.jep.2013.10.022_bib32","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.3892\/ijo_00000776","article-title":"Angiotensin II induces tumor progression and fibrosis in intrahepatic cholangiocarcinoma through an interaction with hepatic stellate cells","volume":"37","author":"Okamoto","year":"2010","journal-title":"Int. J. Oncol."},{"key":"10.1016\/j.jep.2013.10.022_bib33","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.bpg.2006.07.002","article-title":"Hepatocellular carcinoma development in cirrhosis","volume":"21","author":"Okuda","year":"2007","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"10.1016\/j.jep.2013.10.022_bib34","first-page":"1131","article-title":"Aut-i hepatic fibrosis ef fect of Huangqi injection and Danshen injection on 52 cases of liver fibrosis","volume":"30","author":"Peng","year":"2010","journal-title":"Chin. Hosp. Pharm. J."},{"key":"10.1016\/j.jep.2013.10.022_bib35","first-page":"39","article-title":"Effect of silymarin on N-nitrosodiethylamine induced hepatocarcinogenesis in rats","volume":"29","author":"Ramakrishnan","year":"2007","journal-title":"Exp. Oncol."},{"key":"10.1016\/j.jep.2013.10.022_bib36","first-page":"1393","article-title":"Expression of pSmad3L and PAI-1 during the process of DEN-induced hepatic fibrosis-carcinoma in rat","volume":"28","author":"Rui","year":"2012","journal-title":"Chin. Pharmacol. Bull. (Chin.)"},{"key":"10.1016\/j.jep.2013.10.022_bib37","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.mrrev.2011.12.004","article-title":"Mechanistic considerations for human relevance of cancer hazard of di(2-ethylhexyl) phthalate","volume":"750","author":"Rusyn","year":"2012","journal-title":"Mutat. Res."},{"key":"10.1016\/j.jep.2013.10.022_bib38","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1159\/000078001","article-title":"Dietary supplementation of the citrus antioxidant auraptene inhibits N,N-diethylnitrosamineinduced rat hepatocarcinogenesis","volume":"66","author":"Sakata","year":"2004","journal-title":"Oncology"},{"key":"10.1016\/j.jep.2013.10.022_bib39","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.cbi.2007.09.003","article-title":"Attenuation of N-nitrosodiethylamine-induced hepatocellular carcinoma by a novel flavonol-Morin","volume":"171","author":"Sivaramakrishnan","year":"2008","journal-title":"Chem. Biol. Interact."},{"key":"10.1016\/j.jep.2013.10.022_bib40","first-page":"491","article-title":"A standardized extract from Paeonia lactiflora and Astragalus membranaceus attenuates liver fibrosis induced by porcine serum in rats","volume":"29","author":"Sun","year":"2012","journal-title":"Int. J. Mol. Med."},{"key":"10.1016\/j.jep.2013.10.022_bib41","doi-asserted-by":"crossref","first-page":"249","DOI":"10.3892\/ijmm_00000459","article-title":"HCC develops even in the early stage of chronic liver disease in elderly patients with HCV infection","volume":"26","author":"Takata","year":"2010","journal-title":"Int. J. Mol. Med."},{"key":"10.1016\/j.jep.2013.10.022_bib42","first-page":"351","article-title":"Influence of Salvia miltiorrhizand and Astragalus membranaceus on hemodynamics and liver fibrosis indexes in liver cirrhotic patients with portal hypertention","volume":"21","author":"Tan","year":"2001","journal-title":"Chin. J. Integr. Tradit. West. Med."},{"key":"10.1016\/j.jep.2013.10.022_bib43","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1136\/gut.2003.026534","article-title":"Endothelin receptor antagonist TAK-044 arrests and reverses the development of carbon tetrachloride induced cirrhosis in rats","volume":"53","author":"Thirunavukkarasu","year":"2004","journal-title":"Gut"},{"key":"10.1016\/j.jep.2013.10.022_bib44","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.thromres.2012.06.023","article-title":"The biochemistry, physiology and pathological roles of PAI-1 and the requirements for PAI-1 inhibition in vivo","volume":"130","author":"Van De Craen","year":"2012","journal-title":"Thromb. Res."},{"key":"10.1016\/j.jep.2013.10.022_bib45","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1248\/bpb.32.132","article-title":"Anti-hepatitis B virus activities of astragaloside IV isolated from Radix Astragali","volume":"32","author":"Wang","year":"2009","journal-title":"Biol. Pharm. Bull."},{"key":"10.1016\/j.jep.2013.10.022_bib46","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1177\/0960327112444477","article-title":"Involvement of fatty acid metabolism in the hepatotoxicity induced by divalproex sodium","volume":"31","author":"Wang","year":"2012","journal-title":"Hum. Exp. Toxicol."},{"key":"10.1016\/j.jep.2013.10.022_bib47","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.cbi.2006.08.021","article-title":"Antiangiogenic effect of lygodium flexuosum against N-nitrosodiethylamine- induced hepatotoxicity in rats","volume":"164","author":"Wills","year":"2006","journal-title":"Chem.-Biol. Interact."},{"key":"10.1016\/j.jep.2013.10.022_bib48","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/1756-9966-28-112","article-title":"Traditional Chinese medicines in the treatment of hepatocellular cancers: a systematic review and meta-analysis","volume":"28","author":"Wu","year":"2009","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"10.1016\/j.jep.2013.10.022_bib49","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2013.05.004","article-title":"Pharmacokinetics and tolerance of toal astragalosides after intravenous infusion of astragalosides injection in healthy Chinese volunteers","author":"Xu","year":"2013","journal-title":"Phytomedicine"},{"key":"10.1016\/j.jep.2013.10.022_bib50","first-page":"8312","article-title":"Integrin alpha1beta1 and alpha2beta1 are the key regulators of hepatocarcinoma cell invasion across the fibrotic matrix microenvironment","volume":"63","author":"Yang","year":"2003","journal-title":"Cancer Res."},{"key":"10.1016\/j.jep.2013.10.022_bib51","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.jep.2008.04.012","article-title":"Compound Astragalus and Salvia miltiorrhiza extract exerts anti-fibrosis by mediating TGF-beta\/Smad signaling in myofibroblasts","volume":"118","author":"Yang","year":"2008","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2013.10.022_bib52","first-page":"564","article-title":"Abnormal expression of hepatoma- derived gamma-glutamyltransferase subtyping and its early alteration for carcinogenesis of hepatocytes","volume":"3","author":"Yao","year":"2004","journal-title":"Hepatobiliary Pancreat. Dis. Int."},{"key":"10.1016\/j.jep.2013.10.022_bib53","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.3892\/or.2012.2035","article-title":"Swainsonine inhibits growth and potentiates the cytotoxic effect of paclitaxel in hepatocellular carcinoma in vitro and in vivo","volume":"28","author":"You","year":"2012","journal-title":"Oncol. Rep."}],"container-title":["Journal of Ethnopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378874113007290?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378874113007290?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2019,8,2]],"date-time":"2019-08-02T00:54:26Z","timestamp":1564707266000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0378874113007290"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1]]},"references-count":53,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2014,1]]}},"alternative-id":["S0378874113007290"],"URL":"https:\/\/doi.org\/10.1016\/j.jep.2013.10.022","relation":{},"ISSN":["0378-8741"],"issn-type":[{"value":"0378-8741","type":"print"}],"subject":[],"published":{"date-parts":[[2014,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Compound Astragalus and Salvia miltiorrhiza extract suppresses hepatocellular carcinoma progression by inhibiting fibrosis and PAI-1 mRNA transcription","name":"articletitle","label":"Article Title"},{"value":"Journal of Ethnopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jep.2013.10.022","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2013 Elsevier Ireland Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}