{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:55:05Z","timestamp":1790085305683,"version":"4.0.1"},"reference-count":44,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100004858","name":"Sichuan University of Science and Engineering","doi-asserted-by":"publisher","award":["2017RCL66"],"award-info":[{"award-number":["2017RCL66"]}],"id":[{"id":"10.13039\/501100004858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31972942"],"award-info":[{"award-number":["31972942"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["International Immunopharmacology"],"published-print":{"date-parts":[[2021,1]]},"DOI":"10.1016\/j.intimp.2020.107117","type":"journal-article","created":{"date-parts":[[2020,11,6]],"date-time":"2020-11-06T03:34:28Z","timestamp":1604633668000},"page":"107117","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":54,"special_numbering":"C","title":["Bixin attenuates carbon tetrachloride induced oxidative stress, inflammation and fibrosis in kidney by regulating the Nrf2\/TLR4\/MyD88 and PPAR-\u03b3\/TGF-\u03b21\/Smad3 pathway"],"prefix":"10.1016","volume":"90","author":[{"given":"Jie-Qiong","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Jia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Kai","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan-Min","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.intimp.2020.107117_b0005","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.freeradbiomed.2018.08.015","article-title":"Therapeutic potential of bixin in PM2.5 particles-induced lung injury in an Nrf2-dependent manner","volume":"126","author":"Zhang","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.intimp.2020.107117_b0010","doi-asserted-by":"crossref","first-page":"103316","DOI":"10.1016\/j.resp.2019.103316","article-title":"Targeting oxidative stress, proinflammatory cytokines, apoptosis and toll like receptor 4 by empagliflozin to ameliorate bleomycin-induced lung fibrosis","volume":"273","author":"Kabel","year":"2020","journal-title":"Respir. Physiol. Neurobiol."},{"issue":"5","key":"10.1016\/j.intimp.2020.107117_b0015","doi-asserted-by":"crossref","first-page":"4615","DOI":"10.1039\/D0FO00711K","article-title":"Effects of gastrodin against carbon tetrachloride induced kidney inflammation and fibrosis in mice associated with the AMPK\/Nrf2\/HMGB1 pathway","volume":"11","author":"Ma","year":"2020","journal-title":"Food Funct."},{"key":"10.1016\/j.intimp.2020.107117_b0020","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/j.biopha.2017.02.052","article-title":"Bixin ameliorates high fat diet-induced cardiac injury in mice through inflammation and oxidative stress suppression","volume":"89","author":"Xu","year":"2017","journal-title":"Biomed. Pharmacotherapy"},{"key":"10.1016\/j.intimp.2020.107117_b0025","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.freeradbiomed.2018.04.557","article-title":"Nrf2 protects against acute lung injury and inflammation by modulating TLR4 and Akt signaling","volume":"121","author":"Yan","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.intimp.2020.107117_b0030","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.tox.2012.10.025","article-title":"Chlorogenic acid reduces liver inflammation and fibrosis through inhibition of toll-like receptor 4 signaling pathway","volume":"303","author":"Shi","year":"2013","journal-title":"Toxicology"},{"key":"10.1016\/j.intimp.2020.107117_b0035","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/s00210-016-1210-1","article-title":"Gingerol protects against experimental liver fibrosis in rats via suppression of pro-inflammatory and profibrogenic mediators","volume":"389","author":"Algandaby","year":"2016","journal-title":"Naunyn-Schmiedeberg's Arch. Pharmacol."},{"key":"10.1016\/j.intimp.2020.107117_b0040","doi-asserted-by":"crossref","first-page":"7808656","DOI":"10.1155\/2018\/7808656","article-title":"Andrographolide ameliorates liver fibrosis in mice: involvement of TLR4\/NF- \u03ba B and TGF- \u03b2 1\/Smad2 signaling pathways","author":"Lin","year":"2018","journal-title":"Oxid. Med. Cell Longev."},{"key":"10.1016\/j.intimp.2020.107117_b0045","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1016\/j.bbrc.2009.10.162","article-title":"Bixin regulates mRNA expression involved in adipogenesis and enhances insulin sensitivity in 3T3-L1 adipocytes through PPAR\u03b3 activation","volume":"390","author":"Takahashi","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.intimp.2020.107117_b0050","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.fct.2013.02.051","article-title":"Anti-fibrotic effects of puerarin on CCl4-induced hepatic fibrosis in rats possibly through the regulation of PPAR-\u03b3 expression and inhibition of PI3K\/Akt pathway","volume":"56","author":"Guo","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.intimp.2020.107117_b0055","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1093\/ajh\/hpt268","article-title":"L-carnitine attenuates the development of kidney fibrosis in hypertensive rats by upregulating PPAR-\u03b3","volume":"27","author":"Zambrano","year":"2014","journal-title":"Am. J. Hypertens."},{"key":"10.1016\/j.intimp.2020.107117_b0060","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.intimp.2017.09.013","article-title":"Docosahexaenoic acid attenuates carbon tetrachloride-induced hepatic fibrosis in rats","volume":"53","author":"He","year":"2017","journal-title":"Int. Immunopharmacol."},{"issue":"3","key":"10.1016\/j.intimp.2020.107117_b0065","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.bbrc.2015.08.012","article-title":"MicroRNA-130a and -130b enhance activation of hepatic stellate cells by suppressing PPAR\u03b3 expression: a rat fibrosis model study","volume":"465","author":"Lu","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.intimp.2020.107117_b0070","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/0717-6287-47-49","article-title":"Protective effect of bixin on carbon tetrachloride-induced hepatotoxicity in rats","volume":"47","author":"Moreira","year":"2014","journal-title":"Biol. Res."},{"key":"10.1016\/j.intimp.2020.107117_b0075","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.3390\/nu9121371","article-title":"Targeting NRF2 for improved skin barrier function and photoprotection: focus on the achiote-derived apocarotenoid Bixin","volume":"9","author":"de la Vega","year":"2017","journal-title":"Nutrients"},{"key":"10.1016\/j.intimp.2020.107117_b0080","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.fct.2019.02.013","article-title":"Bixin, an apocarotenoid isolated from Bixa orellana L., sensitizes human melanoma cells to dacarbazine-induced apoptosis through ROS-mediated cytotoxicity","volume":"125","author":"de Oliveira J\u00fanior","year":"2019","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.intimp.2020.107117_b0085","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.jare.2015.11.002","article-title":"Phytochemistry biological activities and potential of annatto in natural colorant production for industrial applications-A review","volume":"7","author":"Shahid-Ul-Islam","year":"2016","journal-title":"J. Adv. Res."},{"key":"10.1016\/j.intimp.2020.107117_b0090","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1055\/a-1008-1238","article-title":"Antinociceptive and Anti-Inflammatory Effects of Bixin, a Carotenoid Extracted from the Seeds of Bixa orellana","volume":"85","author":"Pacheco","year":"2019","journal-title":"Planta Med"},{"key":"10.1016\/j.intimp.2020.107117_b0095","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.foodres.2017.08.005","article-title":"Annatto carotenoids attenuate oxidative stress and inflammatory response after high-calorie meal in healthy subjects","volume":"100","author":"Roehrs","year":"2017","journal-title":"Food Res. Int."},{"key":"10.1016\/j.intimp.2020.107117_b0100","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/j.freeradbiomed.2015.08.028","article-title":"Systemic administration of the apocarotenoid bixin protects skin against solar UV-induced damage through activation of NRF2","volume":"89","author":"Tao","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.intimp.2020.107117_b0105","doi-asserted-by":"crossref","first-page":"18760","DOI":"10.1038\/srep18760","article-title":"Bixin protects mice against ventilation-induced lung injury in an NRF2-dependent manner","volume":"6","author":"Tao","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.intimp.2020.107117_b0110","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1039\/C7TX00304H","article-title":"Bixin protects against particle-induced long-term lung injury in an NRF2-dependent manner","volume":"7","author":"Xue","year":"2018","journal-title":"Toxicol. Res. (Camb)"},{"issue":"2","key":"10.1016\/j.intimp.2020.107117_b0115","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.jep.2004.11.019","article-title":"Caffeic acid phenethyl ester protects kidneys against carbon tetrachloride toxicity in rats","volume":"97","author":"Ogeturk","year":"2005","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.intimp.2020.107117_b0120","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.etp.2016.08.005","article-title":"In vivo protective effect of phosphatidylcholine on carbon tetrachloride induced nephrotoxicity","volume":"68","author":"Kim","year":"2016","journal-title":"Exp. Toxicol. Pathol."},{"key":"10.1016\/j.intimp.2020.107117_b0125","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.taap.2016.09.011","article-title":"A mouse model of alcoholic liver fibrosis-associated acute kidney injury identifies key molecular pathways","volume":"310","author":"Furuya","year":"2016","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"10.1016\/j.intimp.2020.107117_b0130","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.fct.2018.10.024","article-title":"Role of AMPK pathway in lead-induced endoplasmic reticulum stress in kidney and in paeonol-induced protection in mice","volume":"122","author":"Liu","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.intimp.2020.107117_b0135","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1016\/j.neuro.2007.03.002","article-title":"Differential induction of oxidative impairments in brain regions of male mice following subchronic consumption of Khesari dhal (Lathyrus sativus) and detoxified Khesari dhal","volume":"28","author":"Shinomol","year":"2007","journal-title":"Neurotoxicology"},{"key":"10.1016\/j.intimp.2020.107117_b0140","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.cbi.2018.03.003","article-title":"Protective effect of rutin against carbon tetrachloride-induced oxidative stress, inflammation and apoptosis in mouse kidney associated with the ceramide, MAPKs, p53 and calpain activities","volume":"286","author":"Ma","year":"2018","journal-title":"Chem. Biol. Interact."},{"key":"10.1016\/j.intimp.2020.107117_b0145","doi-asserted-by":"crossref","first-page":"105984","DOI":"10.1016\/j.intimp.2019.105984","article-title":"Paeonol attenuates carbon tetrachloride-induced mouse liver fibrosis and hepatic stellate cell activation associated with the SIRT1\/TGF-\u03b21\/Smad3 and autophagy pathway","volume":"77","author":"Ma","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.intimp.2020.107117_b0150","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1007\/s00204-016-1830-8","article-title":"TLR4-mediated inflammation is a key pathogenic event leading to kidney damage and fibrosis in cyclosporine nephrotoxicity","volume":"91","author":"Gonz\u00e1lez-Guerrero","year":"2017","journal-title":"Arch. Toxicol."},{"key":"10.1016\/j.intimp.2020.107117_b0155","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.2147\/DDDT.S137507","article-title":"Schisandrin B attenuates CCl4-induced liver fibrosis in rats by regulation of Nrf2-ARE and TGF-\u03b2\/Smad signaling pathways","volume":"11","author":"Chen","year":"2017","journal-title":"Drug Des. Devel. Ther."},{"key":"10.1016\/j.intimp.2020.107117_b0160","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.cbi.2013.06.016","article-title":"Protective effects of naringenin on carbon tetrachloride-induced acute nephrotoxicity in mouse kidney","volume":"205","author":"Hermenean","year":"2013","journal-title":"Chem. Biol. Interact."},{"key":"10.1016\/j.intimp.2020.107117_b0165","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.cbi.2019.02.022","article-title":"Protective effects of anthocyanins from bilberry extract in rats exposed to nephrotoxic effects of carbon tetrachloride","volume":"304","author":"Popovi\u0107","year":"2019","journal-title":"Chem. Biol. Interact."},{"key":"10.1016\/j.intimp.2020.107117_b0170","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.ejphar.2016.04.042","article-title":"Isorhamnetin attenuates liver fibrosis by inhibiting TGF-\u03b2\/Smad signaling and relieving oxidative stress","volume":"783","author":"Yang","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.intimp.2020.107117_b0175","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.intimp.2016.04.040","article-title":"Oxymatrine attenuates CCl4-induced hepatic fibrosis via modulation of TLR4-dependent inflammatory and TGF-\u03b21 signaling pathways","volume":"36","author":"Zhao","year":"2016","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.intimp.2020.107117_b0180","doi-asserted-by":"crossref","first-page":"172422","DOI":"10.1016\/j.ejphar.2019.172422","article-title":"Tetramethylpyrazine guards against cisplatin-induced nephrotoxicity in rats through inhibiting HMGB1\/TLR4\/NF-\u03baB and activating Nrf2 and PPAR-\u03b3 signaling pathways","volume":"857","author":"Michel","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.intimp.2020.107117_b0185","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.7150\/ijbs.7.1056","article-title":"Diverse Roles of TGF-\u03b2\/Smads in Renal Fibrosis and Inflammation","volume":"7","author":"Lan","year":"2011","journal-title":"Int. J. Biol. Sci."},{"key":"10.1016\/j.intimp.2020.107117_b0190","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s12291-016-0564-y","article-title":"Transforming growth factor-\u03b21\/Smad3 signaling and redox status in experimentally induced nephrotoxicity: impact of carnosine","volume":"32","author":"Keshk","year":"2017","journal-title":"Indian J. Clin. Biochem."},{"key":"10.1016\/j.intimp.2020.107117_b0195","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/labinvest.2008.104","article-title":"PPAR-gamma agonist attenuates renal interstitial fibrosis and inflammation through reduction of TGF-beta","volume":"89","author":"Kawai","year":"2009","journal-title":"Lab. Invest."},{"key":"10.1016\/j.intimp.2020.107117_b0200","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.3389\/fphys.2018.01033","article-title":"Klotho and PPAR gamma activation mediate the renoprotective effect of losartan in the 5\/6 nephrectomy model","volume":"9","author":"Maquigussa","year":"2018","journal-title":"Front. Physiol."},{"key":"10.1016\/j.intimp.2020.107117_b0205","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1080\/0886022X.2020.1729188","article-title":"PPAR \u03b3\/TLR4\/TGF-\u03b21 axis mediates the protection effect of erythropoietin on cyclosporin A-induced chronic nephropathy in rat","volume":"42","author":"Liu","year":"2020","journal-title":"Ren. Fail."},{"key":"10.1016\/j.intimp.2020.107117_b0210","first-page":"179","article-title":"Effects of Dan-shao-hua-xian on expression of PPAR-gamma and NF-kappa B in rat liver fibrosis","volume":"7","author":"Wang","year":"2008","journal-title":"Hepatobiliary Pancreat. Dis. Int."},{"key":"10.1016\/j.intimp.2020.107117_b0215","doi-asserted-by":"crossref","first-page":"5115","DOI":"10.1039\/C9FO01010F","article-title":"Protective effects of trans-2,3,5,4'-tetrahydroxystilbene 2-O-\u03b2-d-glucopyranoside on liver fibrosis and renal injury induced by CCl4 via down-regulating p-ERK1\/2 and p-Smad1\/2","volume":"10","author":"Long","year":"2019","journal-title":"Food Funct."},{"key":"10.1016\/j.intimp.2020.107117_b0220","first-page":"1","article-title":"Assessment of the hypoglycemic effect of Bixin in alloxan-induced diabetic rats: in vivo and in silico studies","volume":"13","author":"Keita","year":"2020","journal-title":"J. Biomol. Struct. Dyn."}],"container-title":["International Immunopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1567576920335840?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1567576920335840?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T21:44:38Z","timestamp":1762551878000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1567576920335840"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":44,"alternative-id":["S1567576920335840"],"URL":"https:\/\/doi.org\/10.1016\/j.intimp.2020.107117","relation":{},"ISSN":["1567-5769"],"issn-type":[{"value":"1567-5769","type":"print"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Bixin attenuates carbon tetrachloride induced oxidative stress, inflammation and fibrosis in kidney by regulating the Nrf2\/TLR4\/MyD88 and PPAR-\u03b3\/TGF-\u03b21\/Smad3 pathway","name":"articletitle","label":"Article Title"},{"value":"International Immunopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.intimp.2020.107117","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"107117"}}