{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T19:10:13Z","timestamp":1789585813137,"version":"build-2803163510"},"reference-count":54,"publisher":"Cambridge University Press (CUP)","issue":"1","license":[{"start":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T00:00:00Z","timestamp":1614902400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Br J Nutr"],"published-print":{"date-parts":[[2022,1,14]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chronic tubulointerstitial nephropathy (CTIN) is one of the most common kidney diseases. However, treatment for CTIN has multiple limits. Adjuvant therapy through nutritional regulation has become a hot research topic at present. Icariin (ICA), an extraction of Chinese herbal medicine epimedium, has many pharmacological functions including anti-inflammation and tonifying kidney. Selenomethionine (SeMet) possesses the effects of antioxidant and lightening nephrotoxicity. However, little is known about the combined nephroprotection of them. This study was investigated to evaluate the joint effects of ICA and SeMet on CTIN and explore the mechanism. Based on a novel CTIN model developed in our previous study, mice were randomly divided into five groups (a: control; b: model; c: model + ICA; d: model + SeMet; e: model + ICA + SeMet). Renal tubule epithelial cells were treated with cyclosporine A and ochratoxin A without\/with ICA or\/and SeMet. The results showed that ICA or\/and SeMet ameliorated CTIN by inhibiting the uptrends of blood urine nitrogen, serum creatinine, urine protein, urine gravity, histopathological damage degree and collagen I deposition. ICA or\/and SeMet also increased cell proliferation and decreased apoptosis and the expression of transforming growth factor-beta 1 and <jats:italic>\u03b1<\/jats:italic>-smooth muscle actin. Emphatically, ICA and SeMet joint had better nephroprotection than alone in most indexes including fibrosis. Furthermore, ICA and SeMet joint decreased the activation of toll-like receptor 4 (TLR4)\/NF\u03baB pathway induced by CTIN. TLR4 overexpression counteracted the joint protection of ICA and SeMet. Therefore, ICA and SeMet in combination could protect against CTIN through blocking TLR4\/NF\u03baB pathway. The study will provide novel insights to explore an adjuvant therapeutic orientation.<\/jats:p>","DOI":"10.1017\/s0007114521000787","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T09:49:40Z","timestamp":1614937780000},"page":"12-22","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":12,"title":["Combined protective effects of icariin and selenomethionine on novel chronic tubulointerstitial nephropathy models <i>in vivo<\/i> and <i>in vitro<\/i>"],"prefix":"10.1017","volume":"127","author":[{"given":"Lili","family":"Hou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziman","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anyuan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guannan","family":"Le","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuiping","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azhar","family":"Muhmood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Gan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4132-3052","authenticated-orcid":false,"given":"Kehe","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2021,3,5]]},"reference":[{"key":"S0007114521000787_ref30","first-page":"10","article-title":"Ochratoxin A and ochratoxin-producing fungi on cereal grain in China: a review","volume":"32","author":"Liang","year":"2015","journal-title":"Food Addit Contam Part A Chem Anal Control Expo Risk Assess"},{"key":"S0007114521000787_ref53","doi-asserted-by":"publisher","DOI":"10.1038\/nri3523"},{"key":"S0007114521000787_ref46","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2019.152917"},{"key":"S0007114521000787_ref31","first-page":"102","article-title":"Ochratoxin A in meat and meat products","volume":"51","author":"Gareis","year":"2000","journal-title":"Archiv F\u00fcr Lebensmittelhygiene"},{"key":"S0007114521000787_ref36","doi-asserted-by":"publisher","DOI":"10.1186\/s13568-018-0641-0"},{"key":"S0007114521000787_ref34","doi-asserted-by":"publisher","DOI":"10.1248\/yakushi.17-00150"},{"key":"S0007114521000787_ref9","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9051284"},{"key":"S0007114521000787_ref11","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2019.152917"},{"key":"S0007114521000787_ref8","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2016.08.016"},{"key":"S0007114521000787_ref2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfh485"},{"key":"S0007114521000787_ref54","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2011.10.015"},{"key":"S0007114521000787_ref44","first-page":"1826","article-title":"D-Pinitol alleviates cyclosporine A-induced renal tubulointerstitial fibrosis via activating Sirt1 and Nrf2 antioxidant pathways","volume":"41","author":"Koh","year":"2018","journal-title":"Int J Mol Med"},{"key":"S0007114521000787_ref3","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.060002804.x"},{"key":"S0007114521000787_ref43","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2010.88"},{"key":"S0007114521000787_ref33","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.15483"},{"key":"S0007114521000787_ref52","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.12558"},{"key":"S0007114521000787_ref28","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.25425"},{"key":"S0007114521000787_ref10","first-page":"2105","article-title":"Protective effects of icariin on cisplatin-induced acute renal injury in mice","volume":"7","author":"Pei Ma","year":"2015","journal-title":"Am J Transl Res"},{"key":"S0007114521000787_ref41","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e32833e4149"},{"key":"S0007114521000787_ref29","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2019.07.014"},{"key":"S0007114521000787_ref27","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1995.311"},{"key":"S0007114521000787_ref37","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2011.10.015"},{"key":"S0007114521000787_ref49","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2017.05.016"},{"key":"S0007114521000787_ref42","doi-asserted-by":"publisher","DOI":"10.2741\/3389"},{"key":"S0007114521000787_ref19","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-020-02279-5"},{"key":"S0007114521000787_ref18","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10010009"},{"key":"S0007114521000787_ref4","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2010.71"},{"key":"S0007114521000787_ref32","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2353-z"},{"key":"S0007114521000787_ref13","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-019-1307-6"},{"key":"S0007114521000787_ref20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0119808"},{"key":"S0007114521000787_ref5","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2010.475"},{"key":"S0007114521000787_ref26","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2005.09.004"},{"key":"S0007114521000787_ref40","doi-asserted-by":"publisher","DOI":"10.1186\/s12882-018-0867-8"},{"key":"S0007114521000787_ref24","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-198808000-00019"},{"key":"S0007114521000787_ref51","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2017.11.047"},{"key":"S0007114521000787_ref17","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24071298"},{"key":"S0007114521000787_ref12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2011.10.015"},{"key":"S0007114521000787_ref25","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199403150-00029"},{"key":"S0007114521000787_ref6","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-016-3394-5"},{"key":"S0007114521000787_ref23","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(00)70348-9"},{"key":"S0007114521000787_ref47","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.7513"},{"key":"S0007114521000787_ref50","doi-asserted-by":"publisher","DOI":"10.1038\/nm1663"},{"key":"S0007114521000787_ref38","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1021\/tx200085n","article-title":"Reduction of cisplatin-induced nephrotoxicity in vivo by selenomethionine: the effect on cisplatin-DNA adducts","volume":"24","author":"Sar","year":"2011","journal-title":"Chem Res Toxicol"},{"key":"S0007114521000787_ref21","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-020-02279-5"},{"key":"S0007114521000787_ref14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10068-013-0230-6","article-title":"Icariin supplementation protects mice from exercise-induced oxidant stress in liver","volume":"22","author":"Chen","year":"2013","journal-title":"Food Sci Biotechnol"},{"key":"S0007114521000787_ref39","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-009-8535-2"},{"key":"S0007114521000787_ref7","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2015.01.006"},{"key":"S0007114521000787_ref45","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-016-2930-8"},{"key":"S0007114521000787_ref22","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198409133111103"},{"key":"S0007114521000787_ref1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfg464"},{"key":"S0007114521000787_ref15","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/7464872"},{"key":"S0007114521000787_ref16","doi-asserted-by":"publisher","DOI":"10.1002\/2211-5463.12161"},{"key":"S0007114521000787_ref35","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2019.152917"},{"key":"S0007114521000787_ref48","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20031023"}],"container-title":["British Journal of Nutrition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S0007114521000787","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T06:40:14Z","timestamp":1683873614000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0007114521000787\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,5]]},"references-count":54,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1,14]]}},"alternative-id":["S0007114521000787"],"URL":"https:\/\/doi.org\/10.1017\/s0007114521000787","relation":{},"ISSN":["0007-1145","1475-2662"],"issn-type":[{"value":"0007-1145","type":"print"},{"value":"1475-2662","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,5]]},"assertion":[{"value":"\u00a9 The Author(s), 2021. Published by Cambridge University Press on behalf of The Nutrition Society","name":"copyright","label":"Copyright","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}}]}}