{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T22:51:58Z","timestamp":1787611918375,"version":"build-2736575974"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,10,23]],"date-time":"2019-10-23T00:00:00Z","timestamp":1571788800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,10,23]],"date-time":"2019-10-23T00:00:00Z","timestamp":1571788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Subject Construction Program of Shanghai Pudong New District Health and Family Planning Commission","award":["PWZz2017-24"],"award-info":[{"award-number":["PWZz2017-24"]}]},{"name":"Pudong New Area Science and Technology Development Fund","award":["PKJ2017-Y40"],"award-info":[{"award-number":["PKJ2017-Y40"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Complement Altern Med"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Peritoneal fibrosis (PF) remains a serious complication of long-term peritoneal dialysis (PD). The goal of this study was to investigate the anti-fibrotic effects of curcumin on the PF response to PD and its\u2019 mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male Sprague\u2013Dawley rats were infused with 20\u2009mL of 4.25% glucose-based standard PD fluid for 8 consecutive weeks to establish PF model and then divided into five groups: Control, received sham operation and 0.9% physiological saline; PD, received 4.25% standard PD fluid; Curcumin, PD rats injected intraperitoeally with curcumin for 8\u2009weeks at doses of 10, 20 or 40\u2009mg\/kg. Masson\u2019s staining was performed to evaluate the extent of PF. Peritoneal Equilibration Test (PET) was conducted to assess ultrafiltration volume (UFV) and mass transfer of glucose (MTG), quantitative RT-PCR, and immunohistochemistry or western blotting were performed to measure the expression levels of inflammation and fibrosis-associated factors. We also detected the TGF-\u03b21 in peritoneal fluid by ELISA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with the control group, the PD rats showed decreased UFV (2.54\u2009\u00b1\u20090.48 to 9.87\u2009\u00b1\u20090.78\u2009mL,<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05] and increased MTG (18.99\u2009\u00b1\u20090.86 to 10.85\u2009\u00b1\u20090.65\u2009mmol\/kg,<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) as well as obvious fibroproliferative response, with markedly increased peritoneal thickness (178.33\u2009\u00b1\u20094.42 to 25.26\u2009\u00b1\u20090.32um,<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) and higher expression of a-SMA, collagen I and TGF-\u03b21. Treatment with curcumin significantly increased UFV, reduced MTG and peritoneal thickness of PD rats. The elevated TGF-\u03b21 in peritoneal fluid of PD rats was significantly decreased by curcumin. It attenuated the increase in protein and mRNA of TGF-\u03b21, \u03b1-SMA and collagen I in peritoneum of PD rats. The mRNA expressions of TAK1, JNK and p38, as well as the protein expressions of p-TAK1, p-JNK and p-p38 in peritoneum of PD rats were reduced by curcumin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Present results demonstrate that curcumin showed a protective effect on PD-related PF and suggest an implication of TAK1, p38 and JNK pathway in mediating the benefical effects of curcumin.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12906-019-2702-6","type":"journal-article","created":{"date-parts":[[2019,10,23]],"date-time":"2019-10-23T17:03:41Z","timestamp":1571850221000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Curcumin ameliorates peritoneal fibrosis via inhibition of transforming growth factor-activated kinase 1 (TAK1) pathway in a rat model of peritoneal dialysis"],"prefix":"10.1186","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3527-0978","authenticated-orcid":false,"given":"Jun-Li","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Jun","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Zi","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,10,23]]},"reference":[{"key":"2702_CR1","volume":"10","author":"H Htay","year":"2018","unstructured":"Htay H, Johnson DW, Wiggins KJ, Badve SV, Craig JC, Strippoli GF, et al. Biocompatible dialysis fluids for peritoneal dialysis. Cochrane Database Syst Rev. 2018;10:CD007554.","journal-title":"Cochrane Database Syst Rev"},{"key":"2702_CR2","first-page":"472","volume":"29","author":"P Lei","year":"2012","unstructured":"Lei P, Jiang Z, Zhu H, Li X, Su N, Yu X. Poly (ADP-ribose) polymerase-1 in high glucose-induced epithelial-mesenchymal transition during peritoneal fibrosis. Int J Mol Med. 2012;29:472\u20138.","journal-title":"Int J Mol Med"},{"key":"2702_CR3","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1046\/j.1523-1755.2001.059002463.x","volume":"59","author":"H Ha","year":"2001","unstructured":"Ha H, Yu MR, Lee HB. High glucose-induced PKC activation mediates TGF-beta 1 and fibronectin synthesis by peritoneal mesothelial cells. Kidney Int. 2001;59:463\u201370.","journal-title":"Kidney Int"},{"key":"2702_CR4","doi-asserted-by":"publisher","first-page":"2273","DOI":"10.3892\/mmr.2017.6276","volume":"15","author":"L Yang","year":"2017","unstructured":"Yang L, Wu L, Zhang X, Hu Y, Fan Y, Ma J. 1,25(OH)2D3\/VDR attenuates high glucose induced epithelial mesenchymal transition in human peritoneal mesothelial cells via the TGF\u03b2\/Smad3 pathway. Mol Med Rep. 2017;15:2273\u20139.","journal-title":"Mol Med Rep"},{"key":"2702_CR5","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1056\/NEJMoa020809","volume":"348","author":"M Y\u00e1\u00f1ez-M\u00f3","year":"2003","unstructured":"Y\u00e1\u00f1ez-M\u00f3 M, Lara-Pezzi E, Selgas R, Ram\u00edrez-Huesca M, Dom\u00ednguez-Jim\u00e9nez C, Jim\u00e9nez-Heffernan JA, et al. Peritoneal dialysis and epithelial tomesenchymal transition of mesothelial cells. N Engl J Med. 2003;348:403\u201313.","journal-title":"N Engl J Med"},{"key":"2702_CR6","doi-asserted-by":"publisher","unstructured":"Strippoli R, Moreno Vicente R, Battistelli C, Cicchini C, Noce V, Amicone L, et al. Molecular mechanisms underlying peritoneal EMT and fibrosis. Stem Cells Int. 2016. https:\/\/doi.org\/10.1155\/2016\/3543678 .","DOI":"10.1155\/2016\/3543678"},{"key":"2702_CR7","first-page":"58","volume":"27","author":"JN Diao","year":"2011","unstructured":"Diao JN, Sheng MX, Zhu XX, Wang NJ, Zhu CL, He WM. Huangqi (Astragalus membranaceus) injections could improve the dialysis efficiency and reduce peritoneal fibrosis in high permeable peritoneal dialysis treated rats. Nan Jing Zhong Yi Yao Da Xue Xue Bao. 2011;27:58\u201362.","journal-title":"Nan Jing Zhong Yi Yao Da Xue Xue Bao"},{"key":"2702_CR8","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1159\/000430332","volume":"37","author":"L Zhang","year":"2015","unstructured":"Zhang L, Li ZH, He WM, Xu LD, Wang J, Shi J, et al. Effects of Astragaloside IV against the TGF-\u03b21-induced epithelial-to-mesenchymal transition in peritoneal mesothelial cells by promoting smad 7 expression. Cell Physiol Biochem. 2015;37:43\u201354.","journal-title":"Cell Physiol Biochem"},{"key":"2702_CR9","doi-asserted-by":"publisher","first-page":"2006","DOI":"10.1111\/1750-3841.13793","volume":"82","author":"A Shehzad","year":"2017","unstructured":"Shehzad A, Qureshi M, Anwar MN, Lee YS. Multifunctional Curcumin mediate multitherapeutic effects. J Food Sci. 2017;82:2006\u201315.","journal-title":"J Food Sci"},{"key":"2702_CR10","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1007\/s10753-016-0475-3","volume":"40","author":"PS Chauhan","year":"2017","unstructured":"Chauhan PS, Dash D, Singh R. Intranasal Curcumin inhibits pulmonary fibrosis by modulating matrix Metalloproteinase-9 (MMP-9) in ovalbumin-induced chronic asthma. Inflammation. 2017;40:248\u201358.","journal-title":"Inflammation."},{"key":"2702_CR11","first-page":"447","volume":"21","author":"R Huang","year":"2016","unstructured":"Huang R, Liu Y, Xiong Y, Wu H, Wang G, Sun Z, et al. Curcumin protects against liver fibrosis by attenuating infiltration of Gr1hi monocytes through inhibition of monocyte chemoattractant protein-1. Discov Med. 2016;21:447\u201357.","journal-title":"Discov Med"},{"key":"2702_CR12","doi-asserted-by":"publisher","first-page":"1672","DOI":"10.1111\/bph.12131","volume":"169","author":"BB Aggarwal","year":"2013","unstructured":"Aggarwal BB, Gupta SC, Sung B. Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers. Br J Pharmacol. 2013;169:1672\u201392.","journal-title":"Br J Pharmacol"},{"key":"2702_CR13","doi-asserted-by":"publisher","unstructured":"Sun X, Liu Y, Li C, Wang X, Zhu R, Liu C, et al. Recent advances of curcumin in the prevention and treatment of renal fibrosis. Biomed Res Int. 2017. https:\/\/doi.org\/10.1155\/2017\/2418671 .","DOI":"10.1155\/2017\/2418671"},{"key":"2702_CR14","doi-asserted-by":"crossref","unstructured":"Massague' J, Seoane J, Wotton D. Smad transcription factors. Genes Dev. 2005; 19:2783\u20132810.","DOI":"10.1101\/gad.1350705"},{"key":"2702_CR15","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1093\/ndt\/gfp618","volume":"25","author":"J Loureiro","year":"2010","unstructured":"Loureiro J, Schilte M, Aguilera A, Albar-Vizcaino P, Ramirez-Huesca M, et al. BMP-7 blocks mesenchymal conversion of mesothelial cells and prevents peritoneal damage induced by dialysis fluid exposure. Nephrol Dial Transplant. 2010;25:1098\u2013108.","journal-title":"Nephrol Dial Transplant"},{"key":"2702_CR16","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1038\/cr.2009.5","volume":"19","author":"J Xu","year":"2009","unstructured":"Xu J, Lamouille S, Derynck R. TGF-beta-induced epithelial to mesenchymal transition. Cell Res. 2009;19:156\u201372.","journal-title":"Cell Res"},{"key":"2702_CR17","doi-asserted-by":"publisher","first-page":"4321","DOI":"10.1242\/jcs.071647","volume":"123","author":"R Strippoli","year":"2010","unstructured":"Strippoli R, Benedicto I, Foronda M, Perez-Lozano ML, S\u00e1nchez-Perales S, L\u00f3pez-Cabrera M, et al. p38 maintains E-cadherin expression by modulating TAK1-NF-{kappa} B during epithelial-to-mesenchymal transition. J Cell Sci. 2010;123:4321\u201331.","journal-title":"J Cell Sci"},{"key":"2702_CR18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0031492","volume":"7","author":"R Strippoli","year":"2012","unstructured":"Strippoli R, Benedicto I, Perez Lozano ML, Pellinen T, Sandoval P, Lopez-Cabrera M, et al. Inhibition of transforming growth factor-activated kinase 1 (TAK1) blocks and reverses epithelial to mesenchymal transition of mesothelial cells. PLoS One. 2012;7:e31492.","journal-title":"PLoS One"},{"key":"2702_CR19","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1007\/s11684-017-0571-2","volume":"11","author":"Z Zhang","year":"2017","unstructured":"Zhang Z, Jiang N, Ni Z. Strategies for preventing peritoneal fibrosis in peritoneal dialysis patients: new insights based on peritoneal inflammation and angiogenesis. Front Med. 2017;11:349\u201358.","journal-title":"Front Med"},{"key":"2702_CR20","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.phrs.2016.11.017","volume":"115","author":"D Lelli","year":"2017","unstructured":"Lelli D, Sahebkar A, Johnston TP, Pedone C. Curcumin use in pulmonary diseases: state of the art and future perspectives. Pharmacol Res. 2017;115:133\u201348.","journal-title":"Pharmacol Res"},{"key":"2702_CR21","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/j.amjms.2015.12.017","volume":"351","author":"C Ho","year":"2016","unstructured":"Ho C, Hsu YC, Lei CC, Mau SC, Shih YH, Lin CL. Curcumin rescues diabetic renal fibrosis by targeting superoxide-mediated Wnt signaling pathways. Am J Med Sci. 2016;351:286\u201395.","journal-title":"Am J Med Sci"},{"key":"2702_CR22","doi-asserted-by":"publisher","unstructured":"Chaudhary K. Peritoneal dialysis drop-out: causes and prevention strategies. Int J Nephrol. 2011. https:\/\/doi.org\/10.4061\/2011\/434608 .","DOI":"10.4061\/2011\/434608"},{"key":"2702_CR23","doi-asserted-by":"crossref","first-page":"157","DOI":"10.33549\/physiolres.931990","volume":"60","author":"YM Peng","year":"2011","unstructured":"Peng YM, Shu ZJ, Xiao L, Sun L, Tang WB, Huang Y, et al. A new non-uremic rat model of long-term peritoneal dialysis. Physiol Res. 2011;60:157\u201364.","journal-title":"Physiol Res"},{"key":"2702_CR24","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1177\/089686080302300505","volume":"23","author":"CJ Von Ruhland","year":"2003","unstructured":"Von Ruhland CJ, Newman GR, Topley N, Williams JD. Can artifact mimic the pathology of the peritoneal mesothelium? Perit Dial Int. 2003;23:428\u201333.","journal-title":"Perit Dial Int"},{"key":"2702_CR25","doi-asserted-by":"publisher","first-page":"12959","DOI":"10.3390\/ijms150712959","volume":"15","author":"Z Li","year":"2014","unstructured":"Li Z, Zhang L, He W, Zhu C, Yang J, Sheng M. Astragalus membranaceus inhibits peritoneal fibrosis via monocyte chemoattractant protein (MCP)-1 and the transforming growth factor-\u03b21 (TGF-\u03b21) pathway in rats submitted to peritoneal dialysis. Int J Mol Sci. 2014;15:12959\u201371.","journal-title":"Int J Mol Sci"},{"key":"2702_CR26","doi-asserted-by":"publisher","first-page":"1530","DOI":"10.1046\/j.1523-1755.2003.00861.x","volume":"63","author":"AH Yang","year":"2003","unstructured":"Yang AH, Chen JY, Lin JK. Myofibroblastic conversion of mesothelial cells. Kidney Int. 2003;63:1530\u20139.","journal-title":"Kidney Int"},{"key":"2702_CR27","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1681\/ASN.2004060436","volume":"16","author":"PJ Margetts","year":"2005","unstructured":"Margetts PJ, Bonniaud P, Liu L, Hoff CM, Holmes CJ, West-Mays JA, et al. Transient overexpression of TGF-{beta}1 induces epithelial mesenchymal transition in the rodent peritoneum. J Am Soc Nephrol. 2005;16:425\u201336.","journal-title":"J Am Soc Nephrol"},{"key":"2702_CR28","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1038\/gt.2014.116","volume":"22","author":"H Yoshizawa","year":"2015","unstructured":"Yoshizawa H, Morishita Y, Watanabe M, Ishibashi K, Muto S, Kusano E, et al. TGF-\u03b21-siRNA delivery with nanoparticles inhibits peritoneal fibrosis. Gene Ther. 2015;22:333\u201340.","journal-title":"Gene Ther"},{"key":"2702_CR29","doi-asserted-by":"publisher","first-page":"2309","DOI":"10.1111\/febs.13740","volume":"283","author":"S Xiang","year":"2016","unstructured":"Xiang S, Li M, Xie X, Xie Z, Zhou Q, Tian Y, et al. Rapamycin inhibits epithelial-to-mesenchymal transition of peritoneal mesothelium cells through regulation of rho GTPases. FEBS J. 2016;283:2309\u201325.","journal-title":"FEBS J"},{"key":"2702_CR30","doi-asserted-by":"publisher","unstructured":"Xu S, Jiang B, Wang H, Shen C, Chen H, Zeng L. Curcumin suppresses intestinal fibrosis by inhibition of PPAR\u03b3-mediated epithelial-Mesenchymal transition. Evid Based Complement Alternat Med. 2017. https:\/\/doi.org\/10.1155\/2017\/7876064 .","DOI":"10.1155\/2017\/7876064"},{"key":"2702_CR31","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1016\/j.biopha.2018.02.091","volume":"101","author":"L Qin","year":"2018","unstructured":"Qin L, Qin J, Zhen X, Yang Q, Huang L. Curcumin protects against hepatic stellate cells activation and migration by inhibiting the CXCL12\/CXCR4 biological axis in liver fibrosis: a study in vitro and in vivo. Biomed Pharmacother. 2018;101:599\u2013607.","journal-title":"Biomed Pharmacother"},{"key":"2702_CR32","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1007\/s11655-015-2159-5","volume":"23","author":"J Ma","year":"2017","unstructured":"Ma J, Ma SY, Ding CH. Curcumin reduces cardiac fibrosis by inhibiting myofibroblast differentiation and decreasing transforming growth factor \u03b21 and matrix metalloproteinase 9 \/ tissue inhibitor of metalloproteinase 1. Chin J Integr Med. 2017;23:362\u20139.","journal-title":"Chin J Integr Med"},{"key":"2702_CR33","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1007\/s00441-011-1201-y","volume":"347","author":"Y Mu","year":"2012","unstructured":"Mu Y, Gudey SK, Landstr\u00f6m M. Non-Smad signaling pathways. Cell Tissue Res. 2012;347:11\u201320.","journal-title":"Cell Tissue Res"},{"key":"2702_CR34","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1007\/s10753-013-9791-z","volume":"37","author":"X Su","year":"2014","unstructured":"Su X, Zhou G, Wang Y, Yang X, Li L, Yu R, et al. The PPAR\u03b2\/\u03b4 agonist GW501516 attenuates peritonitis in peritoneal fibrosis via inhibition of TAK1-NF\u03baB pathway in rats. Inflammation. 2014;37:729\u201337.","journal-title":"Inflammation."},{"key":"2702_CR35","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1254\/jphs.14173FP","volume":"126","author":"X Zhou","year":"2014","unstructured":"Zhou X, Zhang J, Xu C, Wang W. Curcumin ameliorates renal fibrosis by inhibiting local fibroblast proliferation and extracellular matrix deposition. J Pharmacol Sci. 2014;126:344\u201350.","journal-title":"J Pharmacol Sci"}],"container-title":["BMC Complementary and Alternative Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12906-019-2702-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12906-019-2702-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12906-019-2702-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T23:01:20Z","timestamp":1611615680000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmccomplementalternmed.biomedcentral.com\/articles\/10.1186\/s12906-019-2702-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,23]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["2702"],"URL":"https:\/\/doi.org\/10.1186\/s12906-019-2702-6","relation":{},"ISSN":["1472-6882"],"issn-type":[{"value":"1472-6882","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,23]]},"assertion":[{"value":"23 May 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 October 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 October 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This animal study was approved by animal ethical committee of Shanghai University of Medicine & Health Sciences affiliated Zhoupu Hospital.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"280"}}