{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T02:55:00Z","timestamp":1790132100271,"version":"4.0.1"},"reference-count":44,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,7,12]],"date-time":"2020-07-12T00:00:00Z","timestamp":1594512000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81673664"],"award-info":[{"award-number":["81673664"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2017A030312009"],"award-info":[{"award-number":["2017A030312009"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Wedelolactone exhibits regulatory effects on some inflammatory diseases. However, the anti\u2010inflammatory mechanism of wedelolactone has not been entirely unravelled. Therefore, the present study focuses on investigating the mechanism of wedelolactone on NLRP3 inflammasome in macrophages and its influence on MSU\u2010induced inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>BMDM, J774A.1 and PMA\u2010differentiated THP\u20101 macrophages were primed with LPS and then stimulated with ATP or nigericin or MSU crystal in the presence or absence of wedelolactone. The cell lysates and supernatants were collected to detect NLRP3 inflammasome components such as NLRP3, ASC and caspase 1, as well as pyroptosis and IL\u20101\u03b2 production. In addition, the anti\u2010inflammatory effects of wedelolactone on MSU\u2010induced peritonitis and arthritis mice were also evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that wedelolactone broadly inhibited NLRP3 inflammasome activation and pyroptosis and IL\u20101\u03b2 secretion. Wedelolactone also block ASC oligomerization and speck formation. The inhibitory effects of wedelolactone were abrogated by PKA inhibitor H89, which also attenuated wedelolactone\u2010enhanced Ser\/Thr phosphorylation of NLRP3 at PKA\u2010specific sites. Importantly, wedelolactone could abate MSU\u2010induced IL\u20101\u03b2 production and neutrophils migration into peritoneal cavity, and reduced caspase 1 (p20) and IL\u20101\u03b2 expression in the joint tissue of MSU\u2010induced arthritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results indicate that wedelolactone promotes the Ser\/Thr phosphorylation of NLRP3 to inhibit inflammasome activation and pyroptosis partly through potentiating PKA signalling, thus identifying its potential use for treating MSU\u2010induced peritonitis and gouty arthritis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cpr.12868","type":"journal-article","created":{"date-parts":[[2020,7,13]],"date-time":"2020-07-13T06:15:15Z","timestamp":1594620915000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["Wedelolactone facilitates Ser\/Thr phosphorylation of NLRP3 dependent on PKA signalling to block inflammasome activation and pyroptosis"],"prefix":"10.1111","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2049-1842","authenticated-orcid":false,"given":"Hao","family":"Pan","sequence":"first","affiliation":[{"name":"Research Center for Integrative Medicine School of Basic Medical Sciences Guangzhou University of Chinese Medicine Guangzhou P.R China"},{"name":"Dongguan &amp; Guangzhou University of Chinese Medicine Cooperative Academy of Mathematical Engineering for Chinese Medicine Dongguan P.R China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Lin","sequence":"additional","affiliation":[{"name":"Research Center for Integrative Medicine School of Basic Medical Sciences Guangzhou University of Chinese Medicine Guangzhou P.R China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Dou","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy School of Basic Medical Sciences Guangzhou University of Chinese Medicine Guangzhou P.R China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Fu","sequence":"additional","affiliation":[{"name":"Research Center for Integrative Medicine School of Basic Medical Sciences Guangzhou University of Chinese Medicine Guangzhou P.R China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqing","family":"Yao","sequence":"additional","affiliation":[{"name":"Research Center for Integrative Medicine School of Basic Medical Sciences Guangzhou University of Chinese Medicine Guangzhou P.R China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanyu","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy School of Basic Medical Sciences Guangzhou University of Chinese Medicine Guangzhou P.R China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saixia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Experimental Teaching School of Basic Medical Sciences Guangzhou University of Chinese Medicine Guangzhou P.R China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neng","family":"Wang","sequence":"additional","affiliation":[{"name":"Research Center for Integrative Medicine School of Basic Medical Sciences Guangzhou University of Chinese Medicine Guangzhou P.R China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aijun","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Experimental Teaching School of Basic Medical Sciences Guangzhou University of Chinese Medicine Guangzhou P.R China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xican","family":"Li","sequence":"additional","affiliation":[{"name":"School of Chinese Herbal Medicine Guangzhou University of Chinese Medicine Guangzhou P.R China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengxue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Research Center for Integrative Medicine School of Basic Medical Sciences Guangzhou University of Chinese Medicine Guangzhou P.R China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongfeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Research Center for Integrative Medicine School of Basic Medical Sciences Guangzhou University of Chinese Medicine Guangzhou P.R China"},{"name":"Department of Human Anatomy School of Basic Medical Sciences Guangzhou University of Chinese Medicine Guangzhou P.R China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,12]]},"reference":[{"issue":"6","key":"e_1_2_9_2_1","first-page":"1259","article-title":"Accentuating the prodigious significance of eclipta alba \u2010 an inestimable medicinal plant","volume":"26","author":"Sidra S","year":"2013","journal-title":"Pak J Pharm Sci"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2016.02.003"},{"issue":"4","key":"e_1_2_9_4_1","first-page":"341","article-title":"Antioxidant, cytotoxic and antimicrobial properties of eclipta alba ethanol extract","volume":"1","author":"Uddin M","year":"2010","journal-title":"Int J Biol Med Res"},{"issue":"6","key":"e_1_2_9_5_1","first-page":"863","article-title":"Antimicrobial activities of ethanol extract and coumestans from eclipta alba (L.) hassk (asteraceae)","volume":"28","author":"Lenza VA","year":"2009","journal-title":"Lat Am J Pharm"},{"key":"e_1_2_9_6_1","first-page":"385969","article-title":"Ethnopharmacological significance of eclipta alba (L.) hassk. 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