{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T16:30:40Z","timestamp":1778344240068,"version":"3.51.4"},"reference-count":56,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T00:00:00Z","timestamp":1645574400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81760657"],"award-info":[{"award-number":["81760657"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>ZFP91 positively regulates IL\u20101\u03b2 production in macrophages and may be a potential therapeutic target to treat inflammatory\u2010related diseases. We investigated whether this process is modulated by convallatoxin, which is a cardiac glycoside isolated from the traditional Chinese medicinal plant <jats:italic>Adonis amurensis Regel et Radde<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p><jats:italic>In vitro<\/jats:italic>, the mechanisms by which convallatoxin inhibits ZFP91\u2010regulated IL\u20101\u03b2 expression were investigated using molecular docking, western blotting, RT\u2010PCR, ELISA, immunofluorescence and immunoprecipitation assays.<jats:italic>In vivo<\/jats:italic>, mice liver injury was induced by an intraperitoneal injection of D\u2010GalN and LPS, colitis was induced by oral administration of dextran sulfate sodium (DSS) in drinking water and peritonitis was induced by an intraperitoneal injection of alum.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>We confirmed that convallatoxin inhibited the release of IL\u20101\u03b2 by down\u2010regulating ZFP91. Importantly, we found that convallatoxin significantly reduced K63\u2010linked polyubiquitination of pro\u2010IL\u20101\u03b2 regulated by ZFP91 and decreased the efficacy of pro\u2010IL\u20101\u03b2 cleavage. Moreover, convallatoxin suppressed ZFP91\u2010mediated activation of the non\u2010canonical cysteine\u2010requiring aspartate protease\u20108 (caspase\u20108) inflammasome and MAPK signalling pathways in macrophages. Furthermore, we showed that ZFP91 promoted the assembly of the caspase\u20108 inflammasome complex, whereas convallatoxin treatment reversed this result. Mice <jats:italic>in vivo<\/jats:italic> studies further demonstrated that convallatoxin ameliorated D\u2010GalN\/LPS\u2010induced liver injury, DSS\u2010induced colitis and alum\u2010induced peritonitis by down\u2010regulating ZFP91.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>We show for the first time that convallatoxin\u2010mediated inhibition of ZFP91 is an important regulatory event that prevents inappropriate inflammatory responses to maintain immune homeostasis. This mechanism provides new insight for the development of convallatoxin as a novel anti\u2010inflammatory drug targeting ZFP91.<\/jats:p><\/jats:sec><jats:sec><jats:title>LINKED ARTICLES<\/jats:title><jats:p>This article is part of a themed issue on Inflammation, Repair and Ageing. To view the other articles in this section visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v179.9\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v179.9\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15758","type":"journal-article","created":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T10:10:38Z","timestamp":1637921438000},"page":"1887-1907","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Convallatoxin inhibits IL\u20101\u03b2 production by suppressing zinc finger protein 91 (ZFP91)\u2010mediated pro\u2010IL\u20101\u03b2 ubiquitination and caspase\u20108 inflammasome activity"],"prefix":"10.1111","volume":"179","author":[{"given":"Yue","family":"Xing","sequence":"first","affiliation":[{"name":"Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, 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