{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T19:07:06Z","timestamp":1785179226605,"version":"3.55.0"},"reference-count":34,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["International Immunopharmacology"],"published-print":{"date-parts":[[2015,9]]},"DOI":"10.1016\/j.intimp.2015.08.008","type":"journal-article","created":{"date-parts":[[2015,8,26]],"date-time":"2015-08-26T00:45:09Z","timestamp":1440549909000},"page":"802-807","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":50,"title":["Total glucosides of paeony can reduce the hepatotoxicity caused by Methotrexate and Leflunomide combination treatment of active rheumatoid arthritis"],"prefix":"10.1016","volume":"28","author":[{"given":"Nan","family":"Xiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Mei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao-Jia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Bao","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Xia","family":"Zuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhan-Guo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang-Pei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.intimp.2015.08.008_bb0005","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1196\/annals.1361.116","article-title":"Pathogenesis of rheumatoid arthritis: targeting cytokines","volume":"1051","author":"Zwerina","year":"2005","journal-title":"Ann. N. Y. Acad. Sci."},{"issue":"Suppl. 3","key":"10.1016\/j.intimp.2015.08.008_bb0010","doi-asserted-by":"crossref","first-page":"S265","DOI":"10.1186\/ar578","article-title":"Epidemiology and genetics of rheumatoid arthritis","volume":"4","author":"Silman","year":"2002","journal-title":"Arthritis Res."},{"issue":"6","key":"10.1016\/j.intimp.2015.08.008_bb0015","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1002\/art.23721","article-title":"American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis","volume":"59","author":"Saag","year":"2008","journal-title":"Arthritis Rheum."},{"issue":"3","key":"10.1016\/j.intimp.2015.08.008_bb0020","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1136\/annrheumdis-2013-204573","article-title":"EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update","volume":"73","author":"Smolen","year":"2014","journal-title":"Ann. Rheum. Dis."},{"issue":"9","key":"10.1016\/j.intimp.2015.08.008_bb0025","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1002\/acr.21997","article-title":"Changes in use of disease-modifying antirheumatic drugs for rheumatoid arthritis in the United States during 1983\u20132009","volume":"65","author":"Kim","year":"2013","journal-title":"Arthritis Care Res. (Hoboken)"},{"issue":"1","key":"10.1016\/j.intimp.2015.08.008_bb0030","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1002\/art.1780330116","article-title":"The use of combinations of disease-modifying antirheumatic agents in rheumatoid arthritis","volume":"33","author":"Paulus","year":"1990","journal-title":"Arthritis Rheum."},{"issue":"6","key":"10.1016\/j.intimp.2015.08.008_bb0035","first-page":"591","article-title":"\u201cNo evidence of disease\u201d in rheumatoid arthritis using methotrexate in combination with other drugs: a contemporary goal for rheumatology care?","volume":"15","author":"Pincus","year":"1997","journal-title":"Clin. Exp. Rheumatol."},{"issue":"9164","key":"10.1016\/j.intimp.2015.08.008_bb0040","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1016\/S0140-6736(98)08513-4","article-title":"Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial. FIN-RACo trial group","volume":"353","author":"M\u00f6tt\u00f6nen","year":"1999","journal-title":"Lancet"},{"issue":"9149","key":"10.1016\/j.intimp.2015.08.008_bb0045","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/S0140-6736(98)09403-3","article-title":"Efficacy and safety of leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomised, multicentre trial. European Leflunomide Study Group","volume":"353","author":"Smolen","year":"1999","journal-title":"Lancet"},{"issue":"8","key":"10.1016\/j.intimp.2015.08.008_bb0050","first-page":"1521","article-title":"Combination leflunomide and methotrexate (MTX) therapy for patients with active rheumatoid arthritis failing MTX monotherapy: open-label extension of a randomized, double-blind, placebo controlled trial","volume":"31","author":"Kremer","year":"2004","journal-title":"J. Rheumatol."},{"issue":"7","key":"10.1016\/j.intimp.2015.08.008_bb0055","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1002\/1529-0131(199907)42:7<1322::AID-ANR4>3.0.CO;2-P","article-title":"Pharmacokinetics safety, and efficacy of combination treatment with methotrexate and leflunomide in patients with active rheumatoid arthritis","volume":"42","author":"Weinblatt","year":"1999","journal-title":"Arthritis Rheum."},{"issue":"9","key":"10.1016\/j.intimp.2015.08.008_bb0060","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1002\/1529-0131(200109)44:9<1984::AID-ART346>3.0.CO;2-B","article-title":"Two-year, blinded, randomized, controlled trial of treatment of active rheumatoid arthritis with leflunomide compared with methotrexate. Utilization of leflunomide in the treatment of rheumatoid arthritis trial investigator group","volume":"44","author":"Cohen","year":"2001","journal-title":"Arthritis Rheum."},{"issue":"9","key":"10.1016\/j.intimp.2015.08.008_bb0180","doi-asserted-by":"crossref","first-page":"726","DOI":"10.7326\/0003-4819-137-9-200211050-00007","article-title":"Concomitant leflunomide therapy in patients with active rheumatoid arthritis despite stable doses of methotrexate. A randomized, double-blind, placebocontrolled trial","volume":"137","author":"Kremer","year":"2002","journal-title":"Ann. Intern. Med."},{"key":"10.1016\/j.intimp.2015.08.008_bb0065","first-page":"117","article-title":"Effect of total glucoside of paeony on rheumatoid arthritis patients","volume":"10","author":"Wang","year":"1994","journal-title":"Chin. Pharmacol. Bull."},{"key":"10.1016\/j.intimp.2015.08.008_bb0070","first-page":"211","article-title":"Protective effects of total glucosides of paeony on joint damage in adjuvant arthritis rats","volume":"10","author":"Wang","year":"1996","journal-title":"Chin. J. Pharmacol. Toxicol."},{"issue":"8","key":"10.1016\/j.intimp.2015.08.008_bb0075","first-page":"487","article-title":"A clinical study of total gluosides palony in the treatment of rheumatoid arthritis: a multi-enter trial","volume":"9","author":"Min","year":"2005","journal-title":"Chin. J. Rheumatol."},{"issue":"14","key":"10.1016\/j.intimp.2015.08.008_bb0080","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.3748\/wjg.v11.i14.2124","article-title":"Effects of total glucosides of peony on immunological hepatic fibrosis in rats","volume":"11","author":"Wang","year":"2005","journal-title":"World J. Gastroenterol."},{"issue":"4","key":"10.1016\/j.intimp.2015.08.008_bb0085","doi-asserted-by":"crossref","first-page":"604","DOI":"10.5114\/aoms.2011.24129","article-title":"Protective effects of total glucosides of paeony and the underlying mechanisms in carbon tetrachloride-induced experimental liver injury","volume":"7","author":"Qin","year":"2011","journal-title":"Arch. Med. Sci."},{"issue":"3","key":"10.1016\/j.intimp.2015.08.008_bb0090","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.intimp.2013.01.021","article-title":"Reduced hepatotoxicity by total glucosides of paeony in combination treatment with leflunomide and methotrexate for patients with active rheumatoid arthritis","volume":"15","author":"Chen","year":"2013","journal-title":"Int. Immunopharmacol."},{"issue":"3","key":"10.1016\/j.intimp.2015.08.008_bb0095","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1002\/art.1780310302","article-title":"The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis","volume":"31","author":"Arnett","year":"1988","journal-title":"Arthritis Rheum."},{"issue":"1","key":"10.1016\/j.intimp.2015.08.008_bb0100","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/art.1780380107","article-title":"Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis","volume":"38","author":"Prevoo","year":"1995","journal-title":"Arthritis Rheum."},{"issue":"1","key":"10.1016\/j.intimp.2015.08.008_bb0105","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1002\/art.1780390105","volume":"39","author":"van Gestel","year":"1996","journal-title":"Arthritis Rheum."},{"issue":"1","key":"10.1016\/j.intimp.2015.08.008_bb0110","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.jep.2008.09.028","article-title":"Effects and mechanisms of total glucosides of paeony on synoviocytes activities in rat collagen-induced arthritis","volume":"121","author":"Chang","year":"2009","journal-title":"J. Ethnopharmacol."},{"issue":"5","key":"10.1016\/j.intimp.2015.08.008_bb0115","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1002\/acr.21641","article-title":"2012 Update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis","volume":"64","author":"Singh","year":"2012","journal-title":"Arthritis Care Res. (Hoboken)"},{"issue":"3","key":"10.1016\/j.intimp.2015.08.008_bb0120","doi-asserted-by":"crossref","first-page":"228","DOI":"10.3899\/jrheum.120922","article-title":"The SMILE study\u2014Safety of methotrexate in combination with leflunomide in rheumatoid arthritis","volume":"40","author":"Bird","year":"2013","journal-title":"J. Rheumatol."},{"issue":"1","key":"10.1016\/j.intimp.2015.08.008_bb0125","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1136\/ard.2008.101378","article-title":"Elevated liver enzyme tests among rheumatoid arthritis and psoriatic arthritis patients treated with methotrexate and\/or leflunomide","volume":"69","author":"Curtis","year":"2010","journal-title":"Ann. Rheum. Dis."},{"issue":"1","key":"10.1016\/j.intimp.2015.08.008_bb0135","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.intimp.2012.06.001","article-title":"Mechanisms involved in the therapeutic effects of Paeonia lactiflora Pallas in rheumatoid arthritis","volume":"14","author":"Zhang","year":"2012","journal-title":"Int. Immunopharmacol."},{"issue":"10","key":"10.1016\/j.intimp.2015.08.008_bb0140","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1016\/j.intimp.2005.03.010","article-title":"Total glucosides of paeony suppressed adjuvant arthritis in rats and intervening cytokine-signaling between different types of synoviocytes","volume":"5","author":"Zheng","year":"2005","journal-title":"Int. Immunopharmacol."},{"issue":"5","key":"10.1016\/j.intimp.2015.08.008_bb0150","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s00011-005-1345-x","article-title":"Effects and mechanisms of total glucosides of paeony on joint damage in rat collagen-induced arthritis","volume":"54","author":"Zhu","year":"2005","journal-title":"Inflamm. Res."},{"issue":"3","key":"10.1016\/j.intimp.2015.08.008_bb0155","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.jep.2006.08.019","article-title":"Effects and mechanisms of total glucosides of paeony on adjuvant arthritis in rats","volume":"109","author":"Xu","year":"2007","journal-title":"J. Ethnopharmacol."},{"issue":"6","key":"10.1016\/j.intimp.2015.08.008_bb0160","first-page":"540","article-title":"Comparative study on clinical efficacy of using methotrexate singly or combined with total glucosides of paeony in treating rheumatoid arthritis","volume":"25","author":"Du","year":"2005","journal-title":"Zhongguo Zhong Xi Yi Jie He Za Zhi"},{"issue":"4","key":"10.1016\/j.intimp.2015.08.008_bb0165","first-page":"355","article-title":"Clinical observation on effects of leflunomid and total glucosides of paeony on rheumatoid arthritis","volume":"26","author":"Zhao","year":"2006","journal-title":"Zhongguo Zhong Xi Yi Jie He Za Zhi"},{"issue":"4","key":"10.1016\/j.intimp.2015.08.008_bb0170","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1111\/j.1440-1681.2006.04371.x","article-title":"Protective effect of paeoniflorin on immunological liver injury induced by bacillus Calmette\u2013Guerin plus lipopolysaccharide: modulation of tumour necrosis factor-alpha and interleukin-6 MRNA","volume":"33","author":"Liu","year":"2006","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"issue":"6","key":"10.1016\/j.intimp.2015.08.008_bb0175","first-page":"653","article-title":"Meta-analysis of total glucosides of paeony combined with methotrexate in treatment for rheumatoid arthritis","volume":"19","author":"Wi","year":"2010","journal-title":"Mod. J. Integr. Tradit. Chin. West. Med."}],"container-title":["International Immunopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1567576915300667?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1567576915300667?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:43:48Z","timestamp":1755650628000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1567576915300667"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9]]},"references-count":34,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,9]]}},"alternative-id":["S1567576915300667"],"URL":"https:\/\/doi.org\/10.1016\/j.intimp.2015.08.008","relation":{},"ISSN":["1567-5769"],"issn-type":[{"value":"1567-5769","type":"print"}],"subject":[],"published":{"date-parts":[[2015,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Total glucosides of paeony can reduce the hepatotoxicity caused by Methotrexate and Leflunomide combination treatment of active rheumatoid arthritis","name":"articletitle","label":"Article Title"},{"value":"International Immunopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.intimp.2015.08.008","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2015 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}]}}