{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T07:19:59Z","timestamp":1784272799961,"version":"3.55.0"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T00:00:00Z","timestamp":1612224000000},"content-version":"vor","delay-in-days":32,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing Municipality","doi-asserted-by":"publisher","award":["cstc2020jcyj-msxm3187"],"award-info":[{"award-number":["cstc2020jcyj-msxm3187"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012246","name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81703205"],"award-info":[{"award-number":["81703205"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>Nonalcoholic fatty liver disease is the most common liver disease worldwide. Hepatic steatosis and oxidative stress are the main characteristics of NAFLD (nonalcoholic fatty liver disease), which also affect its prognosis. Bixin acts as novel Nrf2 (NF\u2010E2 p45\u2010related factor 2) activator with the cytoprotection against oxidative stress and inflammation; this study mainly focused on the mechanism of Nrf2 activation by bixin and explored its potential feasibilities in long\u2010term high\u2010fat diet\u2010 (HFD\u2010) caused hepatic steatosis and inflammatory response <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Bixin was found to activate Nrf2 signals by the modification of critical Keap1 (Kelch\u2010like ECH\u2010associated protein 1) cystine and competitive interaction with Keap1 with upregulating P62 mRNA and protein expression. In human liver cells exposed to FFA (free fatty acid), bixin displayed a pronounced cytoprotective activity with upregulation of Nrf2\u2010mediated gene expression, such as PPAR<jats:italic>\u03b1<\/jats:italic> and its targets related with fatty acid oxidation. In HFD\u2010fed mice, systemic administration of bixin attenuated lipid accumulation, decreased oxidant inflammatory damage in the liver, and reduced circulating lipid levels through Nrf2. Different from most of other established inducers, bixin activated Nrf2 signals through two different mechanisms with safe administration for protection of oxidant inflammatory damage and attenuation of lipid accumulation in the <jats:italic>in vivo<\/jats:italic> long\u2010term HFD\u2010fed mice. Bixin represents a prototype Nrf2 activator that displays cytoprotective activity upon system administration targeting hepatic steatosis and oxidant inflammation originating from long\u2010term HFD\u2010fed mice. And bixin\u2010based Nrf2\u2010directed systemic intervention may also provide therapeutic benefit in protecting other organs in the process of metabolic syndrome.<\/jats:p>","DOI":"10.1155\/2021\/6610124","type":"journal-article","created":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T03:22:43Z","timestamp":1612322563000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Bixin Attenuates High\u2010Fat Diet\u2010Caused Liver Steatosis and Inflammatory Injury through Nrf2\/PPAR<i>\u03b1<\/i> Signals"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6765-3829","authenticated-orcid":false,"given":"Shasha","family":"Tao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1517-6119","authenticated-orcid":false,"given":"Youjing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8100-975X","authenticated-orcid":false,"given":"Jianzhong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3362-6347","authenticated-orcid":false,"given":"Hongyan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2175-3346","authenticated-orcid":false,"given":"Yu","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,2]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2015.3"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2016.05.003"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2016.3"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.09.003"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-017-0436-0"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.11.013"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0104-9"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu11102536"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2016.12.022"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.12.059"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20030285"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2004.11.040"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/8165458"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.00435"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2017.05.015"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2012.08.028"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2017.05.019"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.5117"},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.1039\/C7FO01051F"},{"key":"e_1_2_10_20_2","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.12101"},{"key":"e_1_2_10_21_2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20030326"},{"key":"e_1_2_10_22_2","doi-asserted-by":"publisher","DOI":"10.1039\/C7TX00304H"},{"key":"e_1_2_10_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0095228"},{"key":"e_1_2_10_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02742-14"},{"key":"e_1_2_10_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.02.052"},{"key":"e_1_2_10_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep18760"},{"key":"e_1_2_10_27_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.0c03674"},{"key":"e_1_2_10_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2015.08.028"},{"key":"e_1_2_10_29_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.225680.113"},{"key":"e_1_2_10_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2019.100942"},{"key":"e_1_2_10_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2018.03.022"},{"key":"e_1_2_10_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1305687110"},{"key":"e_1_2_10_33_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.096545"},{"key":"e_1_2_10_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2008.03.003"},{"key":"e_1_2_10_35_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-1439"},{"key":"e_1_2_10_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2018.07.002"},{"key":"e_1_2_10_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-017-1415-1"},{"key":"e_1_2_10_38_2","doi-asserted-by":"publisher","DOI":"10.1021\/jf303639f"},{"key":"e_1_2_10_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01748-12"},{"key":"e_1_2_10_40_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2018.00210"},{"key":"e_1_2_10_41_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28251"},{"key":"e_1_2_10_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2021"},{"key":"e_1_2_10_43_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2018.00188"},{"key":"e_1_2_10_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.12.012"},{"key":"e_1_2_10_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/bs.acr.2018.05.002"},{"key":"e_1_2_10_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.32"}],"container-title":["Oxidative Medicine and Cellular Longevity"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2021\/6610124.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2021\/6610124.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/2021\/6610124","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T18:26:09Z","timestamp":1723055169000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/2021\/6610124"}},"subtitle":[],"editor":[{"given":"Si","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":46,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1155\/2021\/6610124"],"URL":"https:\/\/doi.org\/10.1155\/2021\/6610124","archive":["Portico"],"relation":{},"ISSN":["1942-0900","1942-0994"],"issn-type":[{"value":"1942-0900","type":"print"},{"value":"1942-0994","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"2020-10-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"6610124"}}