{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T19:11:44Z","timestamp":1793128304299,"version":"4.5.0"},"reference-count":62,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:00:00Z","timestamp":1643328000000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009991","name":"Jilin Provincial Department of Finance","doi-asserted-by":"crossref","award":["JLSCZT2019-019"],"award-info":[{"award-number":["JLSCZT2019-019"]}],"id":[{"id":"10.13039\/501100009991","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100009991","name":"Jilin Provincial Department of Finance","doi-asserted-by":"crossref","award":["2017ZX10103004"],"award-info":[{"award-number":["2017ZX10103004"]}],"id":[{"id":"10.13039\/501100009991","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Projects of Major Infectious Disease Control and Prevention of China","award":["JLSCZT2019-019"],"award-info":[{"award-number":["JLSCZT2019-019"]}]},{"name":"National Projects of Major Infectious Disease Control and Prevention of China","award":["2017ZX10103004"],"award-info":[{"award-number":["2017ZX10103004"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:p>Neutrophils release chromatin and antimicrobial proteins to trap and kill microbes, which is termed as neutrophil extracellular trap (NET) formation. NETs play a pivotal role in host defense against infection. However, emerging evidence indicated that NETs also contribute to an exaggerated inflammatory response and organic injuries in sepsis. Zingerone, a natural compound extracted from <jats:italic>Zingiber officinale<\/jats:italic>, exerts antioxidant, anti\u2010inflammatory, and antioncogenic properties. In this study, we found that treatment with zingerone reduced organ injury and improved the outcome in a cecal ligation puncture\u2010 (CLP\u2010) induced polymicrobial sepsis model. Administration of zingerone also alleviates reactive oxygen species (ROS) accumulation and systematic inflammation in septic mice and inhibits neutrophil extracellular traps (NETs) formation <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. Furthermore, inhibition of nuclear factor erythroid 2\u2010related factor 2 (Nrf2) with its specific antagonist significantly counteracted the suppressive effects of zingerone on ROS and NETs and retarded the protective role of zingerone against sepsis\u2010associated organ injury. In addition, exposure to zingerone does not affect phagocytic activity of neutrophils in vitro and bacterial dissemination in vivo. Above all, our results indicate that zingerone treatment obviously attenuates NET formation and inflammatory response via Nrf2\u2010mediated ROS inhibition, thus providing a novel therapeutic strategy against sepsis\u2010induced injury.<\/jats:p>","DOI":"10.1155\/2022\/3990607","type":"journal-article","created":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T17:05:25Z","timestamp":1643389525000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Zingerone Inhibits the Neutrophil Extracellular Trap Formation and Protects against Sepsis via Nrf2\u2010Mediated ROS Inhibition"],"prefix":"10.1155","volume":"2022","author":[{"given":"Yingjie","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dexiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Jie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7940-4339","authenticated-orcid":false,"given":"Han","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1646-2491","authenticated-orcid":false,"given":"Liping","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6471-1819","authenticated-orcid":false,"given":"Xiaoxue","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3036-2374","authenticated-orcid":false,"given":"Dan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,28]]},"reference":[{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0287"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1204242"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13613-017-0319-9"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2013.130142"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12308"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.105"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000639"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019002329"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2847"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-07-587709"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40635-014-0021-2"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.05.015"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2987"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7673"},{"key":"e_1_2_9_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2020.119836"},{"key":"e_1_2_9_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00227"},{"key":"e_1_2_9_17_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200606027"},{"key":"e_1_2_9_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2020.165664"},{"key":"e_1_2_9_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2007.09.085"},{"key":"e_1_2_9_20_2","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/816364"},{"key":"e_1_2_9_21_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25215127"},{"key":"e_1_2_9_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0106536"},{"key":"e_1_2_9_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14540"},{"key":"e_1_2_9_24_2","doi-asserted-by":"publisher","DOI":"10.1039\/D0FO01583K"},{"key":"e_1_2_9_25_2","doi-asserted-by":"publisher","DOI":"10.3791\/51066"},{"key":"e_1_2_9_26_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005743"},{"key":"e_1_2_9_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.05.085"},{"key":"e_1_2_9_28_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21103503"},{"key":"e_1_2_9_29_2","doi-asserted-by":"publisher","DOI":"10.7150\/thno.33872"},{"key":"e_1_2_9_30_2","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8820651"},{"key":"e_1_2_9_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471142735.im0320s110"},{"key":"e_1_2_9_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-020-0524-1"},{"key":"e_1_2_9_33_2","first-page":"400","article-title":"Study of the protective effects of dexamethasone on multiple organ injury in rats with severe acute pancreatitis","volume":"8","author":"Zhang X. P.","year":"2007","journal-title":"Journal of the Pancreas: JOP"},{"key":"e_1_2_9_34_2","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/5985209"},{"key":"e_1_2_9_35_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092385"},{"key":"e_1_2_9_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2006.01.056"},{"key":"e_1_2_9_37_2","doi-asserted-by":"publisher","DOI":"10.1159\/000319909"},{"key":"e_1_2_9_38_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1242255"},{"key":"e_1_2_9_39_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-016-2798-7"},{"key":"e_1_2_9_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.118382"},{"key":"e_1_2_9_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2014.10.057"},{"key":"e_1_2_9_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2013.12.028"},{"key":"e_1_2_9_43_2","doi-asserted-by":"publisher","DOI":"10.1080\/13510002.2021.1907518"},{"key":"e_1_2_9_44_2","doi-asserted-by":"publisher","DOI":"10.1089\/sur.2016.021"},{"key":"e_1_2_9_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/ilar\/ilx007"},{"key":"e_1_2_9_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2011.01.001"},{"key":"e_1_2_9_47_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000151049.19253.54"},{"key":"e_1_2_9_48_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2011.1829"},{"key":"e_1_2_9_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01326"},{"key":"e_1_2_9_50_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000282072.56245.91"},{"key":"e_1_2_9_51_2","doi-asserted-by":"publisher","DOI":"10.1097\/MEJ.0000000000000589"},{"key":"e_1_2_9_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-018-0039-z"},{"key":"e_1_2_9_53_2","doi-asserted-by":"publisher","DOI":"10.1159\/000489829"},{"key":"e_1_2_9_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.183"},{"key":"e_1_2_9_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep37252"},{"key":"e_1_2_9_56_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-019-2407-8"},{"key":"e_1_2_9_57_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00325"},{"key":"e_1_2_9_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-021-00491-3"},{"key":"e_1_2_9_59_2","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.3660"},{"key":"e_1_2_9_60_2","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/8678267"},{"key":"e_1_2_9_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.107117"},{"key":"e_1_2_9_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2515"}],"container-title":["Oxidative Medicine and Cellular Longevity"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2022\/3990607.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/omcl\/2022\/3990607.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/2022\/3990607","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:44:42Z","timestamp":1748911482000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/2022\/3990607"}},"subtitle":[],"editor":[{"given":"Abdur","family":"Rauf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,1]]},"references-count":62,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1155\/2022\/3990607"],"URL":"https:\/\/doi.org\/10.1155\/2022\/3990607","archive":["Portico"],"relation":{},"ISSN":["1942-0900","1942-0994"],"issn-type":[{"value":"1942-0900","type":"print"},{"value":"1942-0994","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1]]},"assertion":[{"value":"2021-10-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"3990607"}}