{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:00:27Z","timestamp":1791172827664,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T00:00:00Z","timestamp":1675814400000},"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":["21961142009"],"award-info":[{"award-number":["21961142009"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82000793"],"award-info":[{"award-number":["82000793"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LY22H070004"],"award-info":[{"award-number":["LY22H070004"]}],"id":[{"id":"10.13039\/501100004731","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":[[2023,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>The NLR family pyrin domain\u2010containing 3 (NLRP3) inflammasome is activated in many inflammatory conditions. So far, no low MW compounds inhibiting NLRP3 have entered clinical use. Identification of naturally occurring NLRP3 inhibitors may be beneficial to the design and development of compounds targeting NLRP3. Alantolactone is a phytochemical from a traditional Chinese medicinal plant with anti\u2010inflammatory activity, but its precise target remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>A bank of phytochemicals was screened for inhibitors of NLRP3\u2010driven production of IL\u20101\u03b2 in cultures of bone\u2010marrow\u2010derived macrophages from female C57BL\/6 mice. Models of gouty arthritis and acute lung injury in male C57BL\/6J mice were used to determine the in vivo effects of the most potent compound.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>Among the 150 compounds screened in vitro, alantolactone exhibited the highest inhibitory activity against LPS\u2009+\u2009ATP\u2010induced production of IL\u20101\u03b2 in macrophages, suppressing IL\u20101\u03b2 secretion, caspase\u20101 activation and pyroptosis. Alantolactone directly bound to the NACHT domain of NLRP3 to inhibit activation and assembly of NLRP3 inflammasomes. Molecular simulation analysis suggested that Arg335 in NLRP3 was a critical residue for alantolactone binding, leading to suppression of NLRP3\u2013NEK7 interaction. In vivo studies confirmed significant alleviation by alantolactone of two NLRP3\u2010driven inflammatory conditions, acute lung injury and gouty arthritis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>The phytochemical alantolactone inhibited activity of NLRP3 inflammasomes by directly targeting the NACHT domain of NLRP3. Alantolactone shows great potential in the treatment of NLRP3\u2010driven diseases and could lead to the development of novel NLRP3 inhibitors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.16036","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T14:24:16Z","timestamp":1674224656000},"page":"1634-1647","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Discovery of alantolactone as a naturally occurring NLRP3 inhibitor to alleviate NLRP3\u2010driven inflammatory diseases in mice"],"prefix":"10.1111","volume":"180","author":[{"given":"Weifeng","family":"Li","sequence":"first","affiliation":[{"name":"Chemical Biology Research Center, School of Pharmaceutical Sciences Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haowen","family":"Xu","sequence":"additional","affiliation":[{"name":"Chemical Biology 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