{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T21:07:41Z","timestamp":1788815261091,"version":"build-2803163510"},"reference-count":49,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82570889"],"award-info":[{"award-number":["82570889"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biochemical Pharmacology"],"published-print":{"date-parts":[[2026,11]]},"DOI":"10.1016\/j.bcp.2026.118373","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T15:18:35Z","timestamp":1787152715000},"page":"118373","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"P2","title":["Rhein alleviates lethal renal ischemia\u2013reperfusion injury via inhibition of NLRP3 inflammasomes by targeting PPAR\u03b3"],"prefix":"10.1016","volume":"253","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9748-4114","authenticated-orcid":false,"given":"Cheng","family":"Fu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyi","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangli","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahui","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0574-9785","authenticated-orcid":false,"given":"Gang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bcp.2026.118373_b0005","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1016\/S0140-6736(15)00344-X","article-title":"Acute kidney injury in China: a cross-sectional survey","volume":"386","author":"Yang","year":"2015","journal-title":"Lancet"},{"key":"10.1016\/j.bcp.2026.118373_b0010","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1016\/j.kint.2020.04.048","article-title":"Intestinal microbiota control acute kidney injury severity by immune modulation","volume":"98","author":"Yang","year":"2020","journal-title":"Kidney Int."},{"key":"10.1016\/j.bcp.2026.118373_b0015","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/nrneph.2011.16","article-title":"Pathophysiology of ischemic acute kidney injury","volume":"7","author":"Asif","year":"2011","journal-title":"Nat. Rev. Nephrol."},{"key":"10.1016\/j.bcp.2026.118373_b0020","doi-asserted-by":"crossref","first-page":"52","DOI":"10.5500\/wjt.v5.i2.52","article-title":"Update on ischemia-reperfusion injury in kidney transplantation: Pathogenesis and treatment","volume":"5","author":"Maurizio","year":"2015","journal-title":"World J. Transplant."},{"key":"10.1016\/j.bcp.2026.118373_b0025","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.3389\/fimmu.2020.01346","article-title":"Metabolic Flexibility and Innate Immunity in Renal Ischemia Reperfusion Injury: the Fine Balance between Adaptive Repair and Tissue Degeneration","volume":"11","author":"Alessandra","year":"2020","journal-title":"Front. Immunol."},{"key":"10.1016\/j.bcp.2026.118373_b0030","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1038\/nm.2507","article-title":"Ischemia and reperfusion\u2014from mechanism to translation","volume":"17","author":"Holger","year":"2011","journal-title":"Nat. Med."},{"key":"10.1016\/j.bcp.2026.118373_b0035","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/s41572-021-00284-z","article-title":"Acute kidney injury","volume":"7","author":"John","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"10.1016\/j.bcp.2026.118373_b0040","doi-asserted-by":"crossref","first-page":"15029","DOI":"10.1096\/fj.202000261RRR","article-title":"BAY61-3606 protects kidney from acute ischemia\/reperfusion injury through inhibiting spleen tyrosine kinase and suppressing inflammatory macrophage response","volume":"34","author":"Tan","year":"2020","journal-title":"FASEB J."},{"key":"10.1016\/j.bcp.2026.118373_b0045","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1089\/ars.2016.6665","article-title":"Oxidant Mechanisms in Renal Injury and Disease","volume":"25","author":"Brian","year":"2016","journal-title":"Antioxid. Redox Signal."},{"key":"10.1016\/j.bcp.2026.118373_b0050","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.7150\/thno.50905","article-title":"Mitochondrial ROS promote mitochondrial dysfunction and inflammation in ischemic acute kidney injury by disrupting TFAM-mediated mtDNA maintenance","volume":"11","author":"Meng","year":"2021","journal-title":"Theranostics"},{"key":"10.1016\/j.bcp.2026.118373_b0055","doi-asserted-by":"crossref","DOI":"10.1016\/j.redox.2020.101504","article-title":"Oral high dose vitamin B12 decreases renal superoxide and post-ischemia\/reperfusion injury in mice","volume":"32","author":"Li","year":"2020","journal-title":"Redox Biol."},{"key":"10.1016\/j.bcp.2026.118373_b0060","doi-asserted-by":"crossref","DOI":"10.1016\/j.biomaterials.2022.121686","article-title":"Ceria nanoparticles prophylactic used for renal ischemia-reperfusion injury treatment by attenuating oxidative stress and inflammatory response","volume":"287","author":"Zhou","year":"2022","journal-title":"Biomaterials"},{"key":"10.1016\/j.bcp.2026.118373_b0065","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s11658-023-00457-6","article-title":"Empagliflozin improves renal ischemia-reperfusion injury by reducing inflammation and enhancing mitochondrial fusion through AMPK-OPA1 pathway promotion","volume":"28","author":"Yang","year":"2023","journal-title":"Cell. Mol. Biol. Lett."},{"key":"10.1016\/j.bcp.2026.118373_b0070","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1038\/nri.2016.151","article-title":"Homeostasis-altering molecular processes as mechanisms of inflammasome activation","volume":"17","author":"Liston","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.bcp.2026.118373_b0075","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.cmet.2017.06.018","article-title":"Inflammasomes on the Crossroads of Innate Immune Recognition and Metabolic Control","volume":"26","author":"Tomasz","year":"2017","journal-title":"Cell Metab."},{"key":"10.1016\/j.bcp.2026.118373_b0080","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/s41573-023-00822-2","article-title":"Drugging the NLRP3 inflammasome: from signalling mechanisms to therapeutic targets","volume":"23","author":"Lieselotte Vande","year":"2023","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.bcp.2026.118373_b0085","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/s41581-019-0158-z","article-title":"The role of inflammasomes in kidney disease","volume":"15","author":"Komada","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"10.1016\/j.bcp.2026.118373_b0090","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/s41420-021-00719-2","article-title":"NLRP3 associated with chronic kidney disease progression after ischemia\/reperfusion-induced acute kidney injury","volume":"7","author":"Zheng","year":"2021","journal-title":"Cell Death Discov."},{"key":"10.1016\/j.bcp.2026.118373_b0095","doi-asserted-by":"crossref","first-page":"20388","DOI":"10.1073\/pnas.0908698106","article-title":"Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome","volume":"106","author":"Shankar","year":"2009","journal-title":"PNAS"},{"key":"10.1016\/j.bcp.2026.118373_b0100","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1007\/s00109-023-02330-7","article-title":"Acid-sensing ion channel 1a exacerbates renal ischemia\u2013reperfusion injury through the NF-\u03baB\/NLRP3 inflammasome pathway","volume":"101","author":"Yan","year":"2023","journal-title":"J. Mol. Med."},{"key":"10.1016\/j.bcp.2026.118373_b0105","article-title":"Variants inALDH1A2reveal an anti-inflammatory role for retinoic acid and a new class of disease-modifying drugs in osteoarthritis","volume":"14","author":"Longji","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.bcp.2026.118373_b0110","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.envint.2023.108345","article-title":"Combined exposure to deoxynivalenol facilitates lipid metabolism disorder in high-fat-diet-induced obesity mice","volume":"182","author":"Jin","year":"2023","journal-title":"Environ. Int."},{"key":"10.1016\/j.bcp.2026.118373_b0115","doi-asserted-by":"crossref","unstructured":"Ching Chun, Y.;Chih Hsing, W.;Tzu Chen, L.;Yi, C.;Chin Sung, C.;Kuo Ting, L.;Pei Jane, T.; Yau Sheng, T. Inhibitory effect of PPAR\u03b3 on NLRP3 inflammasome activation. Theranostics 2021, 11, 2424-2441.","DOI":"10.7150\/thno.46873"},{"key":"10.1016\/j.bcp.2026.118373_b0120","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s11010-015-2569-x","article-title":"The wnt\/\u03b2-catenin signaling pathway participates in rhein ameliorating kidney injury in DN mice","volume":"411","author":"Duan","year":"2016","journal-title":"Mol. Cell. Biochem."},{"key":"10.1016\/j.bcp.2026.118373_b0125","first-page":"1743","article-title":"Rhein attenuates obesity-related glomerulopathy by inhibiting the P2X7R\/NLRP3 inflammasome pathway and protecting podocytes","volume":"28","author":"Wei","year":"2025","journal-title":"Iran. J. Basic Med. Sci."},{"key":"10.1016\/j.bcp.2026.118373_b0130","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.phymed.2018.06.029","article-title":"Rhein protects the myocardiac cells against hypoxia\/reoxygention-induced injury by suppressing GSK3\u03b2 activity","volume":"51","author":"Liu","year":"2018","journal-title":"Phytomedicine"},{"key":"10.1016\/j.bcp.2026.118373_b0135","article-title":"Retinal Microenvironment-Protected Rhein-GFFYE Nanofibers Attenuate Retinal Ischemia-Reperfusion Injury via Inhibiting Oxidative stress and Regulating Microglial\/Macrophage M1\/M2 Polarization","volume":"10","author":"Zhang","year":"2023","journal-title":"Adv. Sci."},{"key":"10.1016\/j.bcp.2026.118373_b0140","first-page":"13","article-title":"Rhein attenuates cerebral ischemia-reperfusion injury via inhibition of ferroptosis through NRF2\/SLC7A11\/GPX4 pathway","volume":"369","author":"Hua","year":"2023","journal-title":"Exp. Neurol."},{"key":"10.1016\/j.bcp.2026.118373_b0145","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1093\/ndt\/gfq466","article-title":"Neutralization of the extracellular HMGB1 released by ischaemic-damaged renal cells protects against renal ischaemia-reperfusion injury","volume":"26","author":"Li","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"10.1016\/j.bcp.2026.118373_b0150","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2021.105867","article-title":"Liraglutide protects against lethal renal ischemia-reperfusion injury by inhibiting high-mobility group box 1 nuclear-cytoplasmic translocation and release","volume":"173","author":"Li","year":"2021","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.bcp.2026.118373_b0155","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1016\/j.immuni.2023.10.004","article-title":"Gasdermin D permeabilization of mitochondrial inner and outer membranes accelerates and enhances pyroptosis","volume":"56","author":"Miao","year":"2023","journal-title":"Immunity"},{"key":"10.1016\/j.bcp.2026.118373_b0160","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2021.106021","article-title":"Histone demethylase UTX aggravates acetaminophen overdose induced hepatotoxicity through dual mechanisms","volume":"175","author":"Huang","year":"2022","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.bcp.2026.118373_b0165","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nri3452","article-title":"Activation and regulation of the inflammasomes","volume":"13","author":"Latz","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.bcp.2026.118373_b0170","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/s41590-021-00869-6","article-title":"Inflammasomes and adaptive immune responses","volume":"22","author":"Deets","year":"2021","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.bcp.2026.118373_b0175","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1002\/mco2.70660","article-title":"The NLRP3 Inflammasome: Mechanisms of Activation, Regulation, and Therapeutic Opportunities","volume":"7","author":"Zou","year":"2026","journal-title":"MedComm"},{"key":"10.1016\/j.bcp.2026.118373_b0180","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1038\/nm.2507","article-title":"Ischemia and reperfusion-from mechanism to translation","volume":"17","author":"Eltzschig","year":"2011","journal-title":"Nat. Med."},{"key":"10.1016\/j.bcp.2026.118373_b0185","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/j.rcl.2023.04.004","article-title":"Renal Transplantation Immediate and late Complications","volume":"61","author":"Kim","year":"2023","journal-title":"Radiol. Clin. n. Am."},{"key":"10.1016\/j.bcp.2026.118373_b0190","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.lfs.2021.119466","article-title":"Hydrogen sulfide reduces pyroptosis and alleviates ischemia-reperfusion-induced acute kidney injury by inhibiting NLRP3 inflammasome","volume":"284","author":"Ni","year":"2021","journal-title":"Life Sci."},{"key":"10.1016\/j.bcp.2026.118373_b0195","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.ejphar.2023.176187","article-title":"Gypenoside XVII attenuates renal ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress and NLRP3 inflammasome-triggered pyroptosis","volume":"962","author":"Wang","year":"2024","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.bcp.2026.118373_b0200","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1007\/s10495-024-02001-z","article-title":"CD8+CD103+iTregs protect against ischemia-reperfusion-induced acute kidney Injury by inhibiting pyroptosis","volume":"29","author":"Chen","year":"2024","journal-title":"Apoptosis"},{"key":"10.1016\/j.bcp.2026.118373_b0205","doi-asserted-by":"crossref","unstructured":"Fidelix, T. S. A.;Soares, B.; Trevisani, V. F. M. Diacerein for osteoarthritis - art. no. CD005117. Cochrane Database of Systematic Reviews 2006, 10.1002\/14651858.CD005117.pub2, 59.","DOI":"10.1002\/14651858.CD005117.pub2"},{"key":"10.1016\/j.bcp.2026.118373_b0210","first-page":"431","article-title":"The Efficacy of Diacerein in Hand Osteoarthritis: a Double-blind, Randomized","volume":"35","author":"Shin","year":"2013","journal-title":"Placebo-Controlled Study. Clin. Ther."},{"key":"10.1016\/j.bcp.2026.118373_b0215","doi-asserted-by":"crossref","DOI":"10.1016\/j.expneurol.2023.114541","article-title":"Rhein attenuates cerebral ischemia-reperfusion injury via inhibition of ferroptosis through NRF2\/SLC7A11\/GPX4 pathway","volume":"369","author":"Liu","year":"2023","journal-title":"Exp. Neurol."},{"key":"10.1016\/j.bcp.2026.118373_b0220","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1142\/S0192415X13500341","article-title":"Rhein Inhibits the Expression of Vascular Cell Adhesion Molecule 1 in Human Umbilical Vein Endothelial Cells with or without Lipopolysaccharide Stimulation","volume":"41","author":"Hu","year":"2013","journal-title":"Am. J. Chin. Med."},{"key":"10.1016\/j.bcp.2026.118373_b0225","first-page":"1261","article-title":"Protective effect of rhein against oxidative stress-related endothelial cell injury","volume":"5","author":"Zhong","year":"2012","journal-title":"Mol. Med. Rep."},{"key":"10.1016\/j.bcp.2026.118373_b0230","first-page":"13","article-title":"An integrated network pharmacology and cell metabolomics approach to reveal the role of rhein, a novel PPAR\u03b1 agonist, against renal fibrosis by activating the PPAR\u03b1\u2013CPT1A axis","volume":"102","author":"Qiming","year":"2022","journal-title":"Phytomedicine"},{"key":"10.1016\/j.bcp.2026.118373_b0235","doi-asserted-by":"crossref","first-page":"4287","DOI":"10.1210\/en.2009-0462","article-title":"Rosiglitazone increases the Expression of Peroxisome Proliferator-Activated Receptor-\u03b3 Target Genes in Adipose Tissue, Liver, and Skeletal Muscle in the Sheep Fetus in late Gestation","volume":"150","author":"Muhlhausler","year":"2009","journal-title":"Endocrinology"},{"key":"10.1016\/j.bcp.2026.118373_b0240","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1111\/apha.12665","article-title":"Peroxisome proliferator-activated receptor activation favours selective subcutaneous lipid deposition by coordinately regulating lipoprotein lipase modulators, fatty acid transporters and lipogenic enzymes","volume":"217","author":"Blanchard","year":"2016","journal-title":"Acta Physiol."},{"key":"10.1016\/j.bcp.2026.118373_b0245","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.freeradbiomed.2025.04.031","article-title":"Secoiridoid-enriched extra virgin olive oil extracts enhance mitochondrial activity and antioxidant response in colorectal cancer cells: the role of Oleacein and Oleocanthal in PPAR\u03b3 interaction","volume":"235","author":"Leo","year":"2025","journal-title":"Free Radic. Biol. Med."}],"container-title":["Biochemical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006295226007124?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006295226007124?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T20:13:11Z","timestamp":1788811991000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0006295226007124"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,11]]},"references-count":49,"alternative-id":["S0006295226007124"],"URL":"https:\/\/doi.org\/10.1016\/j.bcp.2026.118373","relation":{},"ISSN":["0006-2952"],"issn-type":[{"value":"0006-2952","type":"print"}],"subject":[],"published":{"date-parts":[[2026,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Rhein alleviates lethal renal ischemia\u2013reperfusion injury via inhibition of NLRP3 inflammasomes by targeting PPAR\u03b3","name":"articletitle","label":"Article Title"},{"value":"Biochemical Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bcp.2026.118373","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"118373"}}