{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T23:56:34Z","timestamp":1789602994162,"version":"build-2803163510"},"reference-count":69,"publisher":"BMJ","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[2010,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background and aim<\/jats:title>\n                    <jats:p>Chronic cholangiopathies have limited therapeutic options and represent an important indication for liver transplantation. Curcumin, the yellow pigment of the spice turmeric, has pleiotropic actions and attenuates hepatic damage in animal models of chemically-induced liver injury. Whether curcumin has beneficial effects in cholangiopathies is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Potential anticholestatic, anti-inflammatory and antifibrotic mechanisms of curcumin were explored in vivo in Mdr2\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice as a murine model of chronic cholangiopathy; as well as in vitro in a cholangiocyte cell line (HuCCT1) and portal myofibroblasts (MFBs) isolated from Mdr2\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Liver damage, cholestasis and fibrosis were reduced in Mdr2\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice after curcumin feeding. Moreover, curcumin inhibited cholangiocyte proliferation and expression of activation marker vascular cell adhesion molecule-1 in Mdr2\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice. Curcumin\u2014similar to PPAR\u03b3 synthetic agonist troglitazone\u2014directly inhibited TNF-\u03b1-induced inflammatory activation of cholangiocytes in vitro, whereas these beneficial effects of curcumin were largely blocked by a PPAR\u03b3 synthetic antagonist. In addition, curcumin blocked proliferation and activation of portal MFBs by inhibiting ERK1\/2 phosphorylation, thus contributing to reduced fibrogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results show that curcumin may have multiple targets in liver including activation of PPAR\u03b3 in cholangiocytes and inhibition of ERK1\/2 signalling in MFBs, thereby modulating several central cellular events in a mouse model of cholangiopathy. Targeting these pathways may be a promising therapeutic approach to cholangiopathies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/gut.2009.186528","type":"journal-article","created":{"date-parts":[[2010,3,23]],"date-time":"2010-03-23T23:04:42Z","timestamp":1269385482000},"page":"521-530","source":"Crossref","is-referenced-by-count":82,"title":["Curcumin improves sclerosing cholangitis in Mdr2\n                    <sup>\u2212\/\u2212<\/sup>\n                    mice by inhibition of cholangiocyte inflammatory response and portal myofibroblast proliferation"],"prefix":"10.1136","volume":"59","author":[{"given":"Anna","family":"Baghdasaryan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Claudel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Kosters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Gumhold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"Silbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Th\u00fcringer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Leski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Fickert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saul J","family":"Karpen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Trauner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2010,3,23]]},"reference":[{"key":"2025120600350339000_59.4.521.1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.14.3338"},{"key":"2025120600350339000_59.4.521.2","first-page":"61","article-title":"The medical management of primary sclerosing cholangitis","volume":"10","author":"Michaels","year":"2008","journal-title":"Medscape J Med"},{"key":"2025120600350339000_59.4.521.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2007.09.007"},{"key":"2025120600350339000_59.4.521.4","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.07.023"},{"key":"2025120600350339000_59.4.521.5","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.08.006"},{"key":"2025120600350339000_59.4.521.6","unstructured":"Aggarwal BB Bhatt ID Ichikawa H . Curcumin \u2014 biological and medicinal properties. 2006:297\u2013368. http:\/\/www.indsaff.com\/10%20Curcumin%20biological.pdf (accessed 10 November 2008)."},{"key":"2025120600350339000_59.4.521.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2007.08.016"},{"key":"2025120600350339000_59.4.521.8","first-page":"153","article-title":"Ethnobotany and research on medicinal plants in India","volume":"185","author":"Jain","year":"1994","journal-title":"Ciba Found Symp"},{"key":"2025120600350339000_59.4.521.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2005.12.007"},{"key":"2025120600350339000_59.4.521.10","doi-asserted-by":"crossref","unstructured":"Oppenheimer A . Turmeric (curumin) in biliary diseases. Lancet 1937:619\u201321.","DOI":"10.1016\/S0140-6736(00)98193-5"},{"key":"2025120600350339000_59.4.521.11","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.1999.00464.x"},{"key":"2025120600350339000_59.4.521.12","doi-asserted-by":"publisher","DOI":"10.1124\/mol.107.039818"},{"key":"2025120600350339000_59.4.521.13","doi-asserted-by":"publisher","DOI":"10.1111\/j.1472-8206.2008.00611.x"},{"key":"2025120600350339000_59.4.521.14","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.bbagen.2007.02.004","article-title":"Curcumin protects against acute liver damage in the rat by inhibiting NF-kappaB, proinflammatory cytokines production and oxidative stress","volume":"1770","author":"Reyes-Gordillo","year":"2007","journal-title":"Biochim Biophys Acta"},{"key":"2025120600350339000_59.4.521.15","doi-asserted-by":"publisher","DOI":"10.1006\/taap.1996.0238"},{"key":"2025120600350339000_59.4.521.16","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204818200"},{"key":"2025120600350339000_59.4.521.17","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.04.009"},{"key":"2025120600350339000_59.4.521.18","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.10.018"},{"key":"2025120600350339000_59.4.521.19","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00027.2002"},{"key":"2025120600350339000_59.4.521.20","doi-asserted-by":"publisher","DOI":"10.1055\/s-2006-960172"},{"key":"2025120600350339000_59.4.521.21","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199810223391707"},{"key":"2025120600350339000_59.4.521.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2005.06.025"},{"key":"2025120600350339000_59.4.521.23","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(81)90261-X"},{"key":"2025120600350339000_59.4.521.24","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(97)70103-3"},{"key":"2025120600350339000_59.4.521.25","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.25542"},{"key":"2025120600350339000_59.4.521.26","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(03)00096-5"},{"key":"2025120600350339000_59.4.521.27","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(03)01068-0"},{"key":"2025120600350339000_59.4.521.28","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3780456"},{"key":"2025120600350339000_59.4.521.29","doi-asserted-by":"publisher","DOI":"10.1007\/s10354-008-0592-1"},{"key":"2025120600350339000_59.4.521.30","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707542"},{"key":"2025120600350339000_59.4.521.31","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M310284200"},{"key":"2025120600350339000_59.4.521.32","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510270514"},{"key":"2025120600350339000_59.4.521.33","first-page":"G269","article-title":"Cytokines induce NF-kappaB in activated but not in quiescent rat hepatic stellate cells","volume":"275","author":"Hellerbrand","year":"1998","journal-title":"Am J Physiol"},{"key":"2025120600350339000_59.4.521.34","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2000.9365"},{"key":"2025120600350339000_59.4.521.35","first-page":"423","article-title":"Increased expression of monocyte chemotactic protein-1 during active hepatic fibrogenesis: correlation with monocyte infiltration","volume":"152","author":"Marra","year":"1998","journal-title":"Am J Pathol"},{"key":"2025120600350339000_59.4.521.36","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90775-7"},{"key":"2025120600350339000_59.4.521.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2007.05.017"},{"key":"2025120600350339000_59.4.521.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2007.12.023"},{"key":"2025120600350339000_59.4.521.39","first-page":"1472","article-title":"Ursodeoxycholic acid does not improve the clinical course of primary sclerosing cholangitis over a 2-year period","volume":"43","author":"De Maria","year":"1996","journal-title":"Hepatogastroenterology"},{"key":"2025120600350339000_59.4.521.40","doi-asserted-by":"crossref","unstructured":"Gong Y Huang ZB Christensen E . Ursodeoxycholic acid for primary biliary cirrhosis. Cochrane Database Syst Rev 2008(3):CD000551. doi:10.1002\/14651858.CD000551.pub2","DOI":"10.1002\/14651858.CD000551.pub2"},{"key":"2025120600350339000_59.4.521.41","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2006.00634.x"},{"key":"2025120600350339000_59.4.521.42","first-page":"1894","article-title":"Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer","volume":"7","author":"Sharma","year":"2001","journal-title":"Clin Cancer Res"},{"key":"2025120600350339000_59.4.521.43","first-page":"1611","article-title":"Untersuchungen \u00fcber Resorption und Ausscheidung des Curcumins","volume":"42","author":"Henning NaK","year":"1934","journal-title":"M\u00fcnchener Medizinische Wochenschrift"},{"key":"2025120600350339000_59.4.521.44","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1097\/01.tp.0000232674.52951.ff","article-title":"Curcumin has potent liver preservation properties in an isolated perfusion model","volume":"82","author":"Chen","year":"2006","journal-title":"Transplantation"},{"key":"2025120600350339000_59.4.521.45","doi-asserted-by":"publisher","DOI":"10.1055\/s-1999-14033"},{"key":"2025120600350339000_59.4.521.46","first-page":"288","article-title":"Effect on curcumin on cholesterol gall-stone induction in mice","volume":"96","author":"Hussain","year":"1992","journal-title":"Indian J Med Res"},{"key":"2025120600350339000_59.4.521.47","doi-asserted-by":"crossref","first-page":"89369","DOI":"10.1155\/2007\/89369","article-title":"Mechanism of the anti-inflammatory effect of curcumin: ppar-gamma activation","volume":"2007","author":"Jacob","year":"2007","journal-title":"PPAR Res"},{"key":"2025120600350339000_59.4.521.48","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2008.20"},{"key":"2025120600350339000_59.4.521.49","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00474.2002"},{"key":"2025120600350339000_59.4.521.50","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20040928"},{"key":"2025120600350339000_59.4.521.51","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00200.2006"},{"key":"2025120600350339000_59.4.521.52","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700532"},{"key":"2025120600350339000_59.4.521.53","first-page":"4931","article-title":"Thiazolidinedione treatment inhibits bile duct proliferation and fibrosis in a rat model of chronic cholestasis","volume":"11","author":"Marra","year":"2005","journal-title":"World J Gastroenterol"},{"key":"2025120600350339000_59.4.521.54","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200524282"},{"key":"2025120600350339000_59.4.521.55","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.4.2247"},{"key":"2025120600350339000_59.4.521.56","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0168-8278(01)00260-4","article-title":"Hepatic stellate cell\/myofibroblast subpopulations in fibrotic human and rat livers","volume":"36","author":"Cassiman","year":"2002","journal-title":"J Hepatol"},{"key":"2025120600350339000_59.4.521.57","doi-asserted-by":"crossref","first-page":"G7","DOI":"10.1152\/ajpgi.2000.279.1.G7","article-title":"Fibrogenesis I. New insights into hepatic stellate cell activation: the simple becomes complex","volume":"279","author":"Eng","year":"2000","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"2025120600350339000_59.4.521.58","doi-asserted-by":"publisher","DOI":"10.1186\/1476-5926-2-S1-S7"},{"key":"2025120600350339000_59.4.521.59","doi-asserted-by":"publisher","DOI":"10.1136\/gut.50.6.891"},{"key":"2025120600350339000_59.4.521.60","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M006577200"},{"key":"2025120600350339000_59.4.521.61","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510310117"},{"key":"2025120600350339000_59.4.521.62","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.33666"},{"key":"2025120600350339000_59.4.521.63","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2008.03.009"},{"key":"2025120600350339000_59.4.521.64","first-page":"G847","article-title":"Rat hepatic stellate cells produce cytokine-induced neutrophil chemoattractant in culture and in vivo","volume":"275","author":"Maher","year":"1998","journal-title":"Am J Physiol"},{"key":"2025120600350339000_59.4.521.65","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1097\/00029330-200705010-00011","article-title":"Effects of curcumin on peroxisome proliferator-activated receptor gamma expression and nuclear translocation\/redistribution in culture-activated rat hepatic stellate cells","volume":"120","author":"Cheng","year":"2007","journal-title":"Chin Med J (Engl)"},{"key":"2025120600350339000_59.4.521.66","doi-asserted-by":"publisher","DOI":"10.1055\/s-2006-933559"},{"key":"2025120600350339000_59.4.521.67","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.14.3350"},{"key":"2025120600350339000_59.4.521.68","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.04.062"},{"key":"2025120600350339000_59.4.521.69","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2007.03353.x"}],"container-title":["Gut"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/gut.2009.186528","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T08:35:17Z","timestamp":1765010117000},"score":1,"resource":{"primary":{"URL":"https:\/\/gut.bmj.com\/lookup\/doi\/10.1136\/gut.2009.186528"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,3,23]]},"references-count":69,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2010,3,23]]},"published-print":{"date-parts":[[2010,4]]}},"alternative-id":["10.1136\/gut.2009.186528"],"URL":"https:\/\/doi.org\/10.1136\/gut.2009.186528","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.4105956.3884054","asserted-by":"object"}]},"ISSN":["0017-5749","1468-3288"],"issn-type":[{"value":"0017-5749","type":"print"},{"value":"1468-3288","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,3,23]]}}}