{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:01:40Z","timestamp":1789984900809,"version":"4.0.1"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by intestinal barrier dysfunction and epithelial cell death. Necroptosis of intestinal epithelial cells (IECs) mediated by the RIPK1\/RIPK3\/MLKL pathway has emerged as a key driver of UC progression. Celastrol, a bioactive compound from Celastrus wilfordii, has shown anti-inflammatory potential, but its effect on necroptosis in UC remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A dextran sulfate sodium (DSS)-induced UC mouse model and a TSZ-induced HT-29 cell necroptosis model were established. Disease activity, colon length, histology, mucus barrier integrity, and tight junction protein expression were evaluated. Western blotting, immunofluorescence, qRT-PCR, and a cellular thermal shift assay (CESTA) were used to assess necroptosis and potential targeting of HSP90.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Celastrol significantly improved body weight, disease activity index, and colon length, while restoring mucus secretion and tight junction proteins (ZO-1, Occludin, Muc-2). It reduced phosphorylation of RIPK1, RIPK3, and MLKL both in vivo and in vitro, decreased pro-inflammatory cytokines (TNF-\u03b1, IL-1\u03b2, IL-6), and attenuated TUNEL-positive IEC death. CESTA indicated that celastrol increased HSP90 thermal stability, suggesting HSP90 engagement.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Celastrol ameliorates DSS-induced colitis by inhibiting HSP90-mediated necroptosis of intestinal epithelial cells, supporting its potential as a candidate for UC therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1866303","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T04:23:18Z","timestamp":1787286198000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Celastrol ameliorates ulcerative colitis by inhibiting HSP90-mediated necroptosis of intestinal epithelial cells"],"prefix":"10.3389","volume":"17","author":[{"given":"Keyi","family":"Lu","sequence":"first","affiliation":[{"name":"Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"Academy of Chinese Medical Sciences, Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"Academy of Chinese Medical Sciences, Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Shi","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"Academy of Chinese Medical Sciences, Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqi","family":"Liu","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"Academy of Chinese Medical Sciences, Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanna","family":"Shao","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"Academy of Chinese Medical Sciences, Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhibin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, School of Anesthesiology, Naval Medical University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erping","family":"Xu","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan University of Chinese Medicine","place":["Zhengzhou, China"]},{"name":"Academy of Chinese Medical Sciences, Henan University of Chinese Medicine","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.lfs.2019.04.025","article-title":"Celastrol-type HSP90 modulators allow for potent cardioprotective effects","volume":"227","author":"Aceros","year":"2019","journal-title":"Life Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1053\/j.gastro.2024.07.046","article-title":"Comparative efficacy of advanced therapies for management of moderate-to-severe ulcerative colitis: 2024 American gastroenterological association evidence synthesis","volume":"167","author":"Ananthakrishnan","year":"2024","journal-title":"Gastroenterology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1038\/s41423-020-00630-3","article-title":"Necroptosis, pyroptosis and apoptosis: an intricate game of cell death","volume":"18","author":"Bertheloot","year":"2001","journal-title":"Cell Mol Immunol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"G32","DOI":"10.1152\/ajpgi.00282.2009","article-title":"Amplification loop of the inflammatory process is induced by P2X7R activation in intestinal epithelial cells in response to neutrophil transepithelial migration","volume":"299","author":"Cesaro","year":"2010","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/s1097-2765(02)00450-1","article-title":"TNF-Induced recruitment and activation of the IKK complex require Cdc37 and Hsp90","volume":"9","author":"Chen","year":"2002","journal-title":"Mol. Cell"},{"key":"B6","doi-asserted-by":"publisher","first-page":"761981","DOI":"10.3389\/fimmu.2021.761981","article-title":"Interaction between commensal bacteria, immune response and the intestinal barrier in inflammatory bowel disease","volume":"12","author":"Chen","year":"2021","journal-title":"Front. Immunol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1857","DOI":"10.1002\/jcb.30321","article-title":"The HSP90 inhibitor 17-DMAG alleviates primary biliary cholangitis via cholangiocyte necroptosis prevention","volume":"123","author":"Chen","year":"2022","journal-title":"J. Cell. Biochem."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1016\/j.jcmgh.2021.02.005","article-title":"New tricks of our old friend the glucocorticoid receptor: from combating ulcerative colitis to preventing associated colorectal cancer","volume":"11","author":"Clarisse","year":"2021","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.yexcr.2017.08.012","article-title":"A novel RIPK1 inhibitor that prevents retinal degeneration in a rat glaucoma model","volume":"359","author":"Do","year":"2017","journal-title":"Exp. Cell Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"102791","DOI":"10.1016\/j.tice.2025.102791","article-title":"Dihydroartemisinin attenuates acetic acid-induced ulcerative colitis in rats: suppression of inflammation and modulation of NF\u03ba\u03b2\/TNF-\u03b1\/RIPK1-mediated necroptosis and apoptosis","volume":"94","author":"Eldesoqui","year":"2025","journal-title":"Tissue Cell"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e37210","DOI":"10.7759\/cureus.37210","article-title":"Successful treatment of linear IgA disease and ulcerative colitis with sulfasalazine","volume":"15","author":"Fletcher","year":"2023","journal-title":"Cureus"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.1016\/j.biopha.2017.09.063","article-title":"Quantitative analysis of necrostatin-1, a necroptosis inhibitor by LC-MS\/MS and the study of its pharmacokinetics and bioavailability","volume":"95","author":"Geng","year":"2017","journal-title":"Biomed. Pharmacother. Biomedecine Pharmacother."},{"key":"B13","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1001\/jama.2023.15389","article-title":"Ulcerative colitis in adults: a review","volume":"330","author":"Gros","year":"2023","journal-title":"JAMA"},{"key":"B14","doi-asserted-by":"publisher","first-page":"112081","DOI":"10.1016\/j.ejmech.2020.112081","article-title":"Celastrol: progresses in structure-modifications, structure-activity relationships, pharmacology and toxicology","volume":"189","author":"Hou","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"B15","doi-asserted-by":"publisher","first-page":"113394","DOI":"10.1016\/j.jep.2020.113394","article-title":"Qingchang huashi formula attenuates DSS-Induced colitis in mice by restoring gut microbiota-metabolism homeostasis and goblet cell function","volume":"266","author":"Hu","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"e2051","DOI":"10.1038\/cddis.2015.386","article-title":"HSP90 activity is required for MLKL oligomerisation and membrane translocation and the induction of necroptotic cell death","volume":"7","author":"Jacobsen","year":"2016","journal-title":"Cell Death Dis."},{"key":"B17","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1038\/nrclinonc.2018.8","article-title":"Targeting the IL-6\/JAK\/STAT3 signalling axis in cancer","volume":"15","author":"Johnson","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1517\/13543784.14.12.1471","article-title":"17-AAG: mechanisms of antitumour activity","volume":"14","author":"Konstantinopoulos","year":"2005","journal-title":"Expert Opin. Investig. Drugs"},{"key":"B19","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1016\/S0140-6736(23)00966-2","article-title":"Ulcerative colitis","volume":"402","author":"Le Berre","year":"2023","journal-title":"Lancet lond. Engl."},{"key":"B20","doi-asserted-by":"publisher","first-page":"441","DOI":"10.3892\/ijmm.2011.601","article-title":"Enhancement of radiation sensitivity in lung cancer cells by celastrol is mediated by inhibition of Hsp90","volume":"27","author":"Lee","year":"2011","journal-title":"Int. J. Mol. Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e16","DOI":"10.4110\/in.2020.20.e16","article-title":"Inhibition of RIPK3 pathway attenuates intestinal inflammation and cell death of inflammatory bowel disease and suppresses necroptosis in peripheral mononuclear cells of ulcerative colitis patients","volume":"20","author":"Lee","year":"2020","journal-title":"Immune Netw."},{"key":"B22","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1016\/j.ajpath.2025.01.004","article-title":"From ulcerative colitis to metastatic colorectal cancer: the neutrophil contribution","volume":"195","author":"Le\u00f3n-Vega","year":"2025","journal-title":"Am. J. Pathol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"10519","DOI":"10.1074\/jbc.275.14.10519","article-title":"Disruption of hsp90 function results in degradation of the death domain kinase, receptor-interacting protein (RIP), and blockage of tumor necrosis factor-induced nuclear factor-kappaB activation","volume":"275","author":"Lewis","year":"2000","journal-title":"J. Biol. Chem."},{"key":"B24","doi-asserted-by":"publisher","first-page":"109974","DOI":"10.1016\/j.intimp.2023.109974","article-title":"Celastrol inhibits necroptosis by attenuating the RIPK1\/RIPK3\/MLKL pathway and confers protection against acute pancreatitis in mice","volume":"117","author":"Liang","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"B25","first-page":"3174","article-title":"Necrostatin-1 reduces intestinal inflammation and colitis-associated tumorigenesis in mice","volume":"5","author":"Liu","year":"2015","journal-title":"Am. J. Cancer Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"153","DOI":"10.3892\/mmr.2025.13518","article-title":"Pristimerin ameliorates colitis-induced intestinal mucosal injury by inhibiting intestinal epithelial necroptosis","volume":"31","author":"Liu","year":"2025","journal-title":"Mol. Med. Rep."},{"key":"B27","doi-asserted-by":"publisher","first-page":"173987","DOI":"10.1016\/j.ejphar.2021.173987","article-title":"Effects of Hsp90 inhibitor on the RIP1-RIP3-MLKL pathway during the development of heart failure in mice","volume":"898","author":"Marunouchi","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1080\/03079457.2016.1141170","article-title":"Hsp90 inhibitor celastrol reinstates growth plate angiogenesis in thiram-induced tibial dyschondroplasia","volume":"45","author":"Nabi","year":"2016","journal-title":"Avian Pathol. J. WVPA"},{"key":"B29","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1111\/jgh.15667","article-title":"Potential benefits of immunomodulator use with vedolizumab for maintenance of remission in ulcerative colitis","volume":"37","author":"Naganuma","year":"2022","journal-title":"J. Gastroenterol. Hepatol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1016\/j.dld.2017.08.017","article-title":"RIP3 AND pMLKL promote necroptosis-induced inflammation and alter membrane permeability in intestinal epithelial cells","volume":"49","author":"Negroni","year":"2017","journal-title":"Dig. Liver Dis. Off. J. Ital. Soc. Gastroenterol. Ital. Assoc. Study Liver"},{"key":"B31","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.tcb.2015.01.001","article-title":"RIPK1 and RIPK3: critical regulators of inflammation and cell death","volume":"25","author":"Newton","year":"2015","journal-title":"Trends Cell Biol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1146\/annurev-biochem-060815-014830","article-title":"Necroptosis and inflammation","volume":"85","author":"Newton","year":"2016","journal-title":"Annu. Rev. Biochem."},{"key":"B33","doi-asserted-by":"publisher","first-page":"99","DOI":"10.3349\/ymj.2021.62.2.99","article-title":"Incidence and prevalence of inflammatory bowel disease across Asia","volume":"62","author":"Park","year":"2021","journal-title":"Yonsei Med. J."},{"key":"B34","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1038\/s41575-020-0326-4","article-title":"Cell death in the gut epithelium and implications for chronic inflammation","volume":"17","author":"Patankar","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"17562848221080793","DOI":"10.1177\/17562848221080793","article-title":"Vedolizumab has longer persistence than infliximab as a first-line biological agent but not as a second-line biological agent in moderate-to-severe ulcerative colitis: real-world registry data from the persistence australian national IBD cohort (PANIC) study","volume":"15","author":"Pudipeddi","year":"2022","journal-title":"Ther. Adv. Gastroenterol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"115075","DOI":"10.1016\/j.taap.2020.115075","article-title":"Celastrol augments sensitivity of NLRP3 to CP-456773 by modulating HSP-90 and inducing autophagy in dextran sodium sulphate-induced colitis in rats","volume":"400","author":"Saber","year":"2020","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1016\/j.cell.2019.10.006","article-title":"Mechanosensation of tight junctions depends on ZO-1 phase separation and flow","volume":"179","author":"Schwayer","year":"2019","journal-title":"Cell"},{"key":"B38","doi-asserted-by":"publisher","first-page":"446","DOI":"10.3389\/fphar.2018.00446","article-title":"Matrine directly activates extracellular heat shock protein 90, resulting in axonal growth and functional recovery in spinal cord injured-mice","volume":"9","author":"Tanabe","year":"2018","journal-title":"Front. Pharmacol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"izad291","DOI":"10.1093\/ibd\/izad291","article-title":"Phosphoproteomics reveals novel insights into the pathogenesis and identifies new therapeutic kinase targets of ulcerative colitis","volume":"30","author":"Tao","year":"2023","journal-title":"Inflamm. Bowel Dis."},{"key":"B40","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1053\/j.gastro.2006.04.020","article-title":"Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection","volume":"131","author":"Van der Sluis","year":"2006","journal-title":"Gastroenterology"},{"key":"B41","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1001\/jama.2023.23814","article-title":"What is ulcerative colitis?","volume":"331","author":"Voelker","year":"2024","journal-title":"JAMA"},{"key":"B42","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1186\/s13046-019-1423-5","article-title":"Necroptosis regulates tumor repopulation after radiotherapy via RIP1\/RIP3\/MLKL\/JNK\/IL8 pathway","volume":"38","author":"Wang","year":"2019","journal-title":"J. Exp. Clin. Cancer Res. CR"},{"key":"B43","doi-asserted-by":"publisher","first-page":"103072","DOI":"10.1016\/j.redox.2024.103072","article-title":"Macrophage Tim-3 maintains intestinal homeostasis in DSS-Induced colitis by suppressing neutrophil necroptosis","volume":"70","author":"Wang","year":"2024","journal-title":"Redox Biol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"153743","DOI":"10.1016\/j.phymed.2021.153743","article-title":"Shaoyao decoction attenuates DSS-Induced ulcerative colitis, macrophage and NLRP3 inflammasome activation through the MKP1\/NF-\u03baB pathway","volume":"92","author":"Wei","year":"2021","journal-title":"Phytomedicine Int. J. Phytother. Phytopharm."},{"key":"B45","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.tibs.2022.10.002","article-title":"The NLRP3 inflammasome: activation and regulation","volume":"48","author":"Xu","year":"2023","journal-title":"Trends biochem. Sci."},{"key":"B46","doi-asserted-by":"publisher","first-page":"e2200755","DOI":"10.1002\/mnfr.202200755","article-title":"Galangin targets HSP90\u03b2 to alleviate ulcerative colitis by controlling fatty acid synthesis and subsequent NLRP3 inflammasome activation","volume":"67","author":"Yang","year":"2023","journal-title":"Mol. Nutr. Food Res."},{"key":"B47","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1007\/s10753-024-02060-z","article-title":"Celastrol regulates the Hsp90-NLRP3 interaction to alleviate rheumatoid arthritis","volume":"48","author":"Yang","year":"2025","journal-title":"Inflammation"},{"key":"B48","doi-asserted-by":"publisher","first-page":"3456","DOI":"10.2174\/1381612829666221122113929","article-title":"Mechanism of HSP90 inhibitor in the treatment of DSS-Induced colitis in mice by inhibiting MAPK pathway and synergistic effect of compound sophorae decoction","volume":"28","author":"Yuan","year":"2022","journal-title":"Curr. Pharm. Des."},{"key":"B49","doi-asserted-by":"publisher","first-page":"175381","DOI":"10.1016\/j.ejphar.2022.175381","article-title":"A novel gut-restricted RIPK1 inhibitor, SZ-15, ameliorates DSS-Induced ulcerative colitis","volume":"937","author":"Zeng","year":"2022","journal-title":"Eur. J. Pharmacol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"35381","DOI":"10.1074\/jbc.M109.051532","article-title":"Characterization of celastrol to inhibit hsp90 and cdc37 interaction","volume":"284","author":"Zhang","year":"2009","journal-title":"J. Biol. Chem."},{"key":"B51","doi-asserted-by":"publisher","first-page":"e2089","DOI":"10.1038\/cddis.2015.390","article-title":"Hsp90 modulates the stability of MLKL and is required for TNF-Induced necroptosis","volume":"7","author":"Zhao","year":"2016","journal-title":"Cell Death Dis."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1170637","DOI":"10.3389\/fphar.2023.1170637","article-title":"Curcumin alleviates experimental colitis in mice by suppressing necroptosis of intestinal epithelial cells","volume":"14","author":"Zhong","year":"2023","journal-title":"Front. Pharmacol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"155399","DOI":"10.1016\/j.phymed.2024.155399","article-title":"Crosstalk between ferroptosis and necroptosis in cerebral ischemia\/reperfusion injury and naotaifang formula exerts neuroprotective effect via HSP90-GCN2-ATF4 pathway","volume":"130","author":"Zhou","year":"2024","journal-title":"Phytomedicine Int. J. Phytother. Phytopharm."}],"updated-by":[{"DOI":"10.3389\/fphar.2026.1974947","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000}}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1866303\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:01:40Z","timestamp":1789981300000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1866303\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,21]]},"references-count":53,"alternative-id":["10.3389\/fphar.2026.1866303"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1866303","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,21]]},"article-number":"1866303"}}