{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T10:36:57Z","timestamp":1783420617911,"version":"3.54.6"},"reference-count":48,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Chemico-Biological Interactions"],"published-print":{"date-parts":[[2025,2]]},"DOI":"10.1016\/j.cbi.2025.111406","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T16:51:12Z","timestamp":1738774272000},"page":"111406","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":11,"special_numbering":"C","title":["Fraxetin inhibits IKK\u03b2, blocks NF-\u03baB pathway and NLRP3 inflammasome activation, and alleviates spleen injury in sepsis"],"prefix":"10.1016","volume":"408","author":[{"given":"Liwei","family":"Huangfu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyang","family":"Fei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingquan","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.cbi.2025.111406_bib1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms25169010","article-title":"Sepsis biomarkers: advancements and clinical applications-A narrative review","volume":"25","author":"He","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.cbi.2025.111406_bib2","article-title":"Mortality in sepsis and septic shock in Europe, North America and Australia between 2009 and 2019- results from a systematic review and meta-analysis","volume":"24","author":"Michael","year":"2020","journal-title":"Crit. Care"},{"key":"10.1016\/j.cbi.2025.111406_bib3","article-title":"Respiratory viral sepsis: epidemiology, pathophysiology, diagnosis and treatment","volume":"29","author":"Xiaoying","year":"2020","journal-title":"Eur. Respir. Rev."},{"key":"10.1016\/j.cbi.2025.111406_bib4","article-title":"Current sepsis therapeutics","volume":"86","author":"Jean-Louis","year":"2022","journal-title":"EBioMedicine"},{"key":"10.1016\/j.cbi.2025.111406_bib5","article-title":"The role of phytochemicals in sepsis: a mechanistic and therapeutic perspective","volume":"47","author":"Babak","year":"2020","journal-title":"Biofactors"},{"key":"10.1016\/j.cbi.2025.111406_bib6","article-title":"Organ dysfunction in sepsis: an ominous trajectory from infection to death","volume":"92","author":"C\u00e9sar","year":"2019","journal-title":"Yale J. Biol. Med."},{"key":"10.1016\/j.cbi.2025.111406_bib7","article-title":"Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy","volume":"13","author":"Richard","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.cbi.2025.111406_bib8","article-title":"Immunosuppression in patients who die of sepsis and multiple organ failure","volume":"306","author":"Jonathan","year":"2011","journal-title":"JAMA"},{"key":"10.1016\/j.cbi.2025.111406_bib9","article-title":"Sepsis promotes splenic production of a protective platelet pool with high CD40 ligand expression","volume":"132","author":"Colin","year":"2022","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.cbi.2025.111406_bib10","article-title":"Liensinine attenuates inflammation and oxidative stress in spleen tissue in an LPS-induced mouse sepsis model","volume":"24","author":"Hanyu","year":"2023","journal-title":"J. Zhejiang Univ. - Sci. B"},{"key":"10.1016\/j.cbi.2025.111406_bib11","article-title":"Ameliorative effect of malvidin on spleen injury in LPS-induced sepsis","volume":"20","author":"Jinfeng","year":"2023","journal-title":"Chem. Biodivers."},{"key":"10.1016\/j.cbi.2025.111406_bib12","article-title":"The role of thioredoxin-1 in suppression sepsis through inhibiting mitochondrial-induced apoptosis in spleen","volume":"47","author":"Guobing","year":"2017","journal-title":"Shock"},{"key":"10.1016\/j.cbi.2025.111406_bib13","article-title":"Targeting NF-\u03baB pathway for the therapy of diseases: mechanism and clinical study","volume":"5","author":"Hui","year":"2020","journal-title":"Signal Transduct. Targeted Ther."},{"key":"10.1016\/j.cbi.2025.111406_bib14","article-title":"Losartan attenuates sepsis-induced cardiomyopathy by regulating macrophage polarization via TLR4-mediated NF-\u03baB and MAPK signaling","volume":"185","author":"Xin-Sen","year":"2022","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.cbi.2025.111406_bib15","article-title":"I\u03baB kinase \u03b2 (IKK\u03b2): structure, transduction mechanism, biological function, and discovery of its inhibitors","volume":"19","author":"Juan","year":"2023","journal-title":"Int. J. Biol. Sci."},{"key":"10.1016\/j.cbi.2025.111406_bib16","article-title":"Thiazolidine-2,4-dione-based irreversible allosteric IKK-\u03b2 kinase inhibitors: optimization into in vivo active anti-inflammatory agents","volume":"188","author":"Ahmed","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.cbi.2025.111406_bib17","article-title":"IKK\u03b2 primes inflammasome formation by recruiting NLRP3 to the trans-Golgi network","volume":"55","author":"Niklas","year":"2022","journal-title":"Immunity"},{"key":"10.1016\/j.cbi.2025.111406_bib18","article-title":"Fraxetin inhibits interleukin-1\u03b2-induced apoptosis, inflammation, and matrix degradation in chondrocytes and protects rat cartilage in vivo","volume":"28","author":"Qing","year":"2021","journal-title":"Saudi Pharm. J."},{"key":"10.1016\/j.cbi.2025.111406_bib19","article-title":"Antifibrotic effects of Fraxetin on carbon tetrachloride-induced liver fibrosis by targeting NF-\u03baB\/I\u03baB\u03b1, MAPKs and Bcl-2\/Bax pathways","volume":"71","author":"Bin","year":"2019","journal-title":"Pharmacol. Rep."},{"key":"10.1016\/j.cbi.2025.111406_bib20","article-title":"Effect of Fraxetin on oxidative damage caused by isoproterenol-induced myocardial infarction in rats","volume":"194","author":"Yu","year":"2022","journal-title":"Appl. Biochem. Biotechnol."},{"key":"10.1016\/j.cbi.2025.111406_bib21","article-title":"Targeting oxidative stress, NLRP3 inflammasome, and autophagy by Fraxetin to combat doxorubicin-induced cardiotoxicity","volume":"14","author":"Ahmed","year":"2021","journal-title":"Pharmaceuticals"},{"key":"10.1016\/j.cbi.2025.111406_bib22","article-title":"Fraxetin ameliorates symptoms of dextran sulphate sodium-induced colitis in mice","volume":"10","author":"Xiuxiu","year":"2024","journal-title":"Heliyon"},{"key":"10.1016\/j.cbi.2025.111406_bib23","article-title":"Deciphering the pharmacological mechanisms of Fraxini Cortex for ulcerative colitis treatment based on network pharmacology and in vivo studies","volume":"23","author":"Tianming","year":"2023","journal-title":"BMC Complement Med Ther."},{"key":"10.1016\/j.cbi.2025.111406_bib24","article-title":"A robust scoring system to evaluate sepsis severity in an animal model","volume":"7","author":"Bradly","year":"2014","journal-title":"BMC Res. Notes"},{"key":"10.1016\/j.cbi.2025.111406_bib25","article-title":"Fraxetin alleviates BLM-induced idiopathic pulmonary fibrosis by inhibiting NCOA4-mediated epithelial cell ferroptosis","volume":"72","author":"Xiaorun","year":"2023","journal-title":"Inflamm. Res."},{"key":"10.1016\/j.cbi.2025.111406_bib26","article-title":"Ferroptotic MSCs protect mice against sepsis via promoting macrophage efferocytosis","volume":"13","author":"Yuchen","year":"2022","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.cbi.2025.111406_bib27","article-title":"A designed self-microemulsifying delivery system: stability and Anti-inflammation in vivo enhancement of dihydromyricetin","volume":"118","author":"Yimei","year":"2024","journal-title":"J. Funct.Foods"},{"key":"10.1016\/j.cbi.2025.111406_bib28","doi-asserted-by":"crossref","DOI":"10.3390\/ijms231911029","article-title":"Iron deposition and ferroptosis in the spleen in a murine model of acute radiation syndrome","volume":"23","author":"Rittase","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.cbi.2025.111406_bib29","doi-asserted-by":"crossref","DOI":"10.26508\/lsa.202402760","article-title":"Mass spectrometry-based proteomic exploration of diverse murine macrophage cellular models","volume":"8","author":"Gudgeon","year":"2025","journal-title":"Life Sci. Alliance"},{"key":"10.1016\/j.cbi.2025.111406_bib30","doi-asserted-by":"crossref","DOI":"10.1002\/ctm2.1449","article-title":"Dracorhodin targeting CMPK2 attenuates inflammation: a novel approach to sepsis therapy","volume":"13","author":"Zhang","year":"2023","journal-title":"Clin. Transl. Med."},{"key":"10.1016\/j.cbi.2025.111406_bib31","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.1001\/jama.2011.1829","article-title":"Immunosuppression in patients who die of sepsis and multiple organ failure","volume":"306","author":"Boomer","year":"2011","journal-title":"JAMA"},{"key":"10.1016\/j.cbi.2025.111406_bib32","doi-asserted-by":"crossref","DOI":"10.1172\/JCI153920","article-title":"Sepsis promotes splenic production of a protective platelet pool with high CD40 ligand expression","volume":"132","author":"Valet","year":"2022","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.cbi.2025.111406_bib33","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.1172\/JCI96832","article-title":"Transcription factor Fra-1 targets arginase-1 to enhance macrophage-mediated inflammation in arthritis","volume":"129","author":"Hannemann","year":"2019","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.cbi.2025.111406_bib34","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1084\/jem.185.10.1759","article-title":"Spermine inhibits proinflammatory cytokine synthesis in human mononuclear cells: a counterregulatory mechanism that restrains the immune response","volume":"185","author":"Zhang","year":"1997","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.cbi.2025.111406_bib35","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.4049\/jimmunol.166.4.2173","article-title":"Cutting edge: stat6-dependent substrate depletion regulates nitric oxide production","volume":"166","author":"Rutschman","year":"2001","journal-title":"J. Immunol."},{"key":"10.1016\/j.cbi.2025.111406_bib36","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1016\/j.celrep.2016.04.001","article-title":"TNF-mediated restriction of arginase 1 expression in myeloid cells triggers type 2 NO synthase activity at the site of infection","volume":"15","author":"Schleicher","year":"2016","journal-title":"Cell Rep."},{"key":"10.1016\/j.cbi.2025.111406_bib37","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1000371","article-title":"Arginase-1-expressing macrophages suppress Th2 cytokine-driven inflammation and fibrosis","volume":"5","author":"Pesce","year":"2009","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.cbi.2025.111406_bib38","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1002\/eji.200839041","article-title":"L-arginine deprivation impairs Leishmania major-specific T-cell responses","volume":"39","author":"Munder","year":"2009","journal-title":"Eur. J. Immunol."},{"key":"10.1016\/j.cbi.2025.111406_bib39","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.00786-2018","article-title":"Neutrophils disturb pulmonary microcirculation in sepsis-induced acute lung injury","volume":"53","author":"Park","year":"2019","journal-title":"Eur. Respir. J."},{"key":"10.1016\/j.cbi.2025.111406_bib40","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/s41419-023-06407-6","article-title":"METTL14 contributes to acute lung injury by stabilizing NLRP3 expression in an IGF2BP2-dependent manner","volume":"15","author":"Cao","year":"2024","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.cbi.2025.111406_bib41","doi-asserted-by":"crossref","DOI":"10.3390\/ph14111188","article-title":"Targeting oxidative stress, NLRP3 inflammasome, and autophagy by Fraxetin to combat doxorubicin-induced cardiotoxicity","volume":"14","author":"Kabel","year":"2021","journal-title":"Pharmaceuticals"},{"key":"10.1016\/j.cbi.2025.111406_bib42","article-title":"Galangin prevents against ethanol-induced intestinal barrier dysfunction and NLRP3 inflammasome activation via NF-\u03baB\/MAPK signaling pathways in mice and caco-2 cells","author":"Zhao","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"10.1016\/j.cbi.2025.111406_bib43","first-page":"1499","article-title":"In vivoFraxetin inhibits interleukin-1\u03b2-induced apoptosis, inflammation, and matrix degradation in chondrocytes and protects rat cartilage","volume":"vol. 28","author":"Wang","year":"2020"},{"key":"10.1016\/j.cbi.2025.111406_bib44","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.pharep.2019.01.008","article-title":"Antifibrotic effects of Fraxetin on carbon tetrachloride-induced liver fibrosis by targeting NF-\u03baB\/I\u03baB\u03b1, MAPKs and Bcl-2\/Bax pathways","volume":"71","author":"Wu","year":"2019","journal-title":"Pharmacol. Rep. : PR."},{"key":"10.1016\/j.cbi.2025.111406_bib45","doi-asserted-by":"crossref","first-page":"4181","DOI":"10.7150\/ijbs.85158","article-title":"I\u03baB kinase \u03b2 (IKK\u03b2): structure, transduction mechanism, biological function, and discovery of its inhibitors","volume":"19","author":"Zhang","year":"2023","journal-title":"Int. J. Biol. Sci."},{"key":"10.1016\/j.cbi.2025.111406_bib46","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.tcb.2020.12.003","article-title":"Expanding the view of IKK: new substrates and new biology","volume":"31","author":"Antonia","year":"2021","journal-title":"Trends Cell Biol."},{"key":"10.1016\/j.cbi.2025.111406_bib47","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1146\/annurev.immunol.18.1.621","article-title":"Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity","volume":"18","author":"Karin","year":"2000","journal-title":"Annu. Rev. Immunol."},{"key":"10.1016\/j.cbi.2025.111406_bib48","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13578-020-00397-0","article-title":"Quercetin and cancer: new insights into its therapeutic effects on ovarian cancer cells","volume":"10","author":"Vafadar","year":"2020","journal-title":"Cell Biosci."}],"container-title":["Chemico-Biological Interactions"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0009279725000365?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0009279725000365?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T12:57:26Z","timestamp":1740488246000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0009279725000365"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":48,"alternative-id":["S0009279725000365"],"URL":"https:\/\/doi.org\/10.1016\/j.cbi.2025.111406","relation":{},"ISSN":["0009-2797"],"issn-type":[{"value":"0009-2797","type":"print"}],"subject":[],"published":{"date-parts":[[2025,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Fraxetin inhibits IKK\u03b2, blocks NF-\u03baB pathway and NLRP3 inflammasome activation, and alleviates spleen injury in sepsis","name":"articletitle","label":"Article Title"},{"value":"Chemico-Biological Interactions","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.cbi.2025.111406","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"111406"}}