{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T08:18:27Z","timestamp":1783153107873,"version":"3.54.6"},"reference-count":30,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82274433"],"award-info":[{"award-number":["82274433"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ethnopharmacology"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1016\/j.jep.2026.121884","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T06:56:40Z","timestamp":1779865000000},"page":"121884","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Xijiao Dihuang decoction ameliorates sepsis by regulating macrophage polarization via activation of the itaconate-mediated Nrf2\/HO-1 pathway"],"prefix":"10.1016","volume":"369","author":[{"given":"Fan","family":"Ge","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeyan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linyi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinguo","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dacheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0692-9069","authenticated-orcid":false,"given":"Fang","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1937-2539","authenticated-orcid":false,"given":"Luyao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2678-2923","authenticated-orcid":false,"given":"Jun","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jep.2026.121884_bib1","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2024.155761","article-title":"Quercetin induces itaconic acid-mediated M1\/M2 alveolar macrophages polarization in respiratory syncytial virus infection","volume":"130","author":"An","year":"2024","journal-title":"Phytomedicine"},{"issue":"8","key":"10.1016\/j.jep.2026.121884_bib2","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2024.114570","article-title":"Endogenously produced itaconate negatively regulates innate-driven cytokine production and drives global ubiquitination in human macrophages","volume":"43","author":"Bourner","year":"2024","journal-title":"Cell Rep."},{"issue":"3","key":"10.1016\/j.jep.2026.121884_bib3","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1097\/CCM.0000000000004224","article-title":"Sepsis among medicare beneficiaries: 1. The burdens of sepsis, 2012-2018","volume":"48","author":"Buchman","year":"2020","journal-title":"Crit. Care Med."},{"issue":"3","key":"10.1016\/j.jep.2026.121884_bib4","doi-asserted-by":"crossref","first-page":"902","DOI":"10.4049\/jimmunol.2001251","article-title":"Macrophage-derived MicroRNA-21 drives overwhelming glycolytic and inflammatory response during sepsis via repression of the PGE(2)\/IL-10 axis","volume":"207","author":"De Melo","year":"2021","journal-title":"J. Immunol."},{"key":"10.1016\/j.jep.2026.121884_bib5","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2024.155446","article-title":"Xijiao Dihuang decoction combined with Yinqiao powder promotes autophagy-dependent ROS decrease to inhibit ROS\/NLRP3\/pyroptosis regulation axis in influenza virus infection","volume":"128","author":"Deng","year":"2024","journal-title":"Phytomedicine"},{"issue":"11","key":"10.1016\/j.jep.2026.121884_bib6","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1007\/s00134-021-06506-y","article-title":"Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021","volume":"47","author":"Evans","year":"2021","journal-title":"Intensive Care Med."},{"key":"10.1016\/j.jep.2026.121884_bib7","doi-asserted-by":"crossref","first-page":"5989","DOI":"10.2147\/JIR.S421232","article-title":"Synergistic enhancement of isoforskolin and dexamethasone against sepsis and acute lung injury mouse models","volume":"16","author":"Fang","year":"2023","journal-title":"J. Inflamm. Res."},{"issue":"8","key":"10.1016\/j.jep.2026.121884_bib8","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1007\/s00134-020-06151-x","article-title":"Incidence and mortality of hospital- and ICU-treated sepsis: results from an updated and expanded systematic review and meta-analysis","volume":"46","author":"Fleischmann-Struzek","year":"2020","journal-title":"Intensive Care Med."},{"issue":"1","key":"10.1016\/j.jep.2026.121884_bib9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BST20190029","article-title":"Biomarkers of inflammation and the etiology of sepsis","volume":"48","author":"Grondman","year":"2020","journal-title":"Biochem. Soc. Trans."},{"issue":"6","key":"10.1016\/j.jep.2026.121884_bib10","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1002\/ddr.21793","article-title":"Paeonol protects melanocytes against hydrogen peroxide-induced oxidative stress through activation of Nrf2 signaling pathway","volume":"82","author":"Guo","year":"2021","journal-title":"Drug Dev. Res."},{"issue":"1","key":"10.1016\/j.jep.2026.121884_bib11","article-title":"Antimicrobial peptide 2K4L inhibits the inflammatory response in macrophages and Caenorhabditis elegans and protects against LPS-induced septic shock in mice","volume":"14","author":"Ji","year":"2024","journal-title":"Sci. Rep."},{"key":"10.1016\/j.jep.2026.121884_bib12","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2021.735530","article-title":"Paeoniflorin suppresses TBHP-induced oxidative stress and apoptosis in human umbilical vein endothelial cells via the Nrf2\/HO-1 signaling pathway and improves skin flap survival","volume":"12","author":"Jiang","year":"2021","journal-title":"Front. Pharmacol."},{"issue":"15","key":"10.1016\/j.jep.2026.121884_bib13","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1089\/ars.2021.0027","article-title":"Oxidative stress and endothelial dysfunction in sepsis and acute inflammation","volume":"35","author":"Joffre","year":"2021","journal-title":"Antioxidants Redox Signal."},{"issue":"1","key":"10.1016\/j.jep.2026.121884_bib14","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.cmet.2016.06.004","article-title":"Itaconate links inhibition of succinate dehydrogenase with macrophage metabolic remodeling and regulation of inflammation","volume":"24","author":"Lampropoulou","year":"2016","journal-title":"Cell Metab."},{"key":"10.1016\/j.jep.2026.121884_bib15","doi-asserted-by":"crossref","first-page":"853","DOI":"10.2147\/JIR.S428305","article-title":"Xijiao dihuang decoction protects against murine sepsis-induced cardiac inflammation and apoptosis via suppressing TLR4\/NF-\u03baB and activating PI3K\/AKT pathway","volume":"17","author":"Li","year":"2024","journal-title":"J. Inflamm. Res."},{"key":"10.1016\/j.jep.2026.121884_bib16","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2022.115802","article-title":"Wutou decoction attenuates the synovial inflammation of collagen-induced arthritis rats via regulating macrophage M1\/M2 type polarization","volume":"301","author":"Lin","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2026.121884_bib17","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2020.110501","article-title":"Xijiao Dihuang decoction improves prognosis of sepsis via inhibition of aerobic glycolysis","volume":"129","author":"Lu","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.jep.2026.121884_bib18","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1007\/s40820-021-00598-3","article-title":"Nanoplatforms for sepsis management: rapid detection\/warning, pathogen elimination and restoring immune homeostasis","volume":"13","author":"Luo","year":"2021","journal-title":"Nano-Micro Lett."},{"issue":"7699","key":"10.1016\/j.jep.2026.121884_bib19","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/nature25986","article-title":"Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1","volume":"556","author":"Mills","year":"2018","journal-title":"Nature"},{"key":"10.1016\/j.jep.2026.121884_bib20","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2024.155694","article-title":"Modified Zhenwu decoction suppresses chronic colitis via targeting macrophage CCR2\/Fyn\/p38 MAPK signaling axis","volume":"129","author":"Mok","year":"2024","journal-title":"Phytomedicine"},{"issue":"19","key":"10.1016\/j.jep.2026.121884_bib21","doi-asserted-by":"crossref","first-page":"10031","DOI":"10.18632\/aging.204989","article-title":"Huangqi Guizhi Wuwu decoction promotes M2 microglia polarization and synaptic plasticity via Sirt1\/NF-\u03baB\/NLRP3 pathway in MCAO rats","volume":"15","author":"Ou","year":"2023","journal-title":"Aging (Albany NY)"},{"issue":"2","key":"10.1016\/j.jep.2026.121884_bib22","doi-asserted-by":"crossref","DOI":"10.1172\/JCI148548","article-title":"The role of itaconate in host defense and inflammation","volume":"132","author":"Peace","year":"2022","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.jep.2026.121884_bib23","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1146\/annurev-immunol-081619-104850","article-title":"Krebs cycle reborn in macrophage immunometabolism","volume":"38","author":"Ryan","year":"2020","journal-title":"Annu. Rev. Immunol."},{"issue":"1","key":"10.1016\/j.jep.2026.121884_bib24","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/s13062-024-00521-x","article-title":"Immune-response gene 1 deficiency aggravates inflammation-triggered cardiac dysfunction by inducing M1 macrophage polarization and aggravating Ly6C(high) monocyte recruitment","volume":"19","author":"Shen","year":"2024","journal-title":"Biol. Direct"},{"key":"10.1016\/j.jep.2026.121884_bib25","doi-asserted-by":"crossref","DOI":"10.1016\/j.redox.2022.102553","article-title":"The signaling pathways and therapeutic potential of itaconate to alleviate inflammation and oxidative stress in inflammatory diseases","volume":"58","author":"Shi","year":"2022","journal-title":"Redox Biol."},{"issue":"8","key":"10.1016\/j.jep.2026.121884_bib26","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The third international consensus definitions for sepsis and septic shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"issue":"Pt A","key":"10.1016\/j.jep.2026.121884_bib27","article-title":"Paeoniflorin-loaded pH-sensitive liposomes alleviate synovial inflammation by altering macrophage polarity via STAT signaling","volume":"101","author":"Wang","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.jep.2026.121884_bib28","article-title":"Therapeutic effects and molecular mechanisms of bioactive compounds against respiratory diseases: traditional Chinese medicine theory and high-frequency use","volume":"12","author":"Wang","year":"2021","journal-title":"Front. Pharmacol."},{"issue":"1","key":"10.1016\/j.jep.2026.121884_bib29","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1186\/s13046-023-02832-9","article-title":"Functional polarization of tumor-associated macrophages dictated by metabolic reprogramming","volume":"42","author":"Zeng","year":"2023","journal-title":"J. Exp. Clin. Cancer Res."},{"issue":"4","key":"10.1016\/j.jep.2026.121884_bib30","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1002\/pros.24652","article-title":"4-Octyl itaconate alleviates experimental autoimmune prostatitis by inhibiting the NLRP3 inflammasome-induced pyroptosis through activating Nrf2\/HO-1 pathway","volume":"84","author":"Zhao","year":"2024","journal-title":"Prostate"}],"container-title":["Journal of Ethnopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378874126007361?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378874126007361?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T07:45:01Z","timestamp":1783151101000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0378874126007361"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":30,"alternative-id":["S0378874126007361"],"URL":"https:\/\/doi.org\/10.1016\/j.jep.2026.121884","relation":{},"ISSN":["0378-8741"],"issn-type":[{"value":"0378-8741","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Xijiao Dihuang decoction ameliorates sepsis by regulating macrophage polarization via activation of the itaconate-mediated Nrf2\/HO-1 pathway","name":"articletitle","label":"Article Title"},{"value":"Journal of Ethnopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jep.2026.121884","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"121884"}}