{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T23:28:36Z","timestamp":1790292516022,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2014,7,8]],"date-time":"2014-07-08T00:00:00Z","timestamp":1404777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tumor necrosis factor (TNF)-\u03b1 is elevated during the acute phase of Kawasaki disease (KD), which damages vascular endothelial cells to cause systemic vasculitis. In the current study, we investigated the potential role of cordycepin on TNF\u03b1 expression in both lipopolysaccharide (LPS)-stimulated macrophages and ex vivo cultured peripheral blood mononuclear cells (PBMCs) of KD patients. We found that cordycepin significantly suppressed LPS-induced TNF\u03b1 expression and production in mouse macrophages (RAW 264.7 cells and bone marrow-derived macrophages (BMDMs)). Meanwhile, cordycepin alleviated TNF\u03b1 production in KD patients\u2019 PBMCs. PBMCs from healthy controls had a much lower level of basal TNF-\u03b1 content than that of KD patients. LPS-induced TNF-\u03b1 production in healthy controls\u2019 PBMCs was also inhibited by cordycepin. For the mechanism study, we discovered that cordycepin activated AMP-activated protein kinase (AMPK) signaling in both KD patients\u2019 PBMCs and LPS-stimulated macrophages, which mediated cordycepin-induced inhibition against TNF\u03b1 production. AMPK inhibition by its inhibitor (compound C) or by siRNA depletion alleviated cordycepin\u2019s effect on TNF\u03b1 production. Further, we found that cordycepin inhibited reactive oxygen species (ROS) production and nuclear factor kappa B (NF-\u03baB) activation in LPS-stimulate RAW 264.7 cells or healthy controls\u2019 PBMCs. PBMCs of KD patients showed higher basal level of ROS and NF-\u03baB activation, which was also inhibited by cordycepin co-treatment. In conclusion, our data showed that cordycepin inhibited TNF\u03b1 production, which was associated with AMPK activation as well as ROS and NF-\u03baB inhibition. The results of this study should have significant translational relevance in managing this devastating disease.<\/jats:p>","DOI":"10.3390\/ijms150712119","type":"journal-article","created":{"date-parts":[[2014,7,8]],"date-time":"2014-07-08T11:15:26Z","timestamp":1404818126000},"page":"12119-12134","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Cordycepin Inhibits Lipopolysaccharide (LPS)-Induced  Tumor Necrosis Factor (TNF)-\u03b1 Production via Activating AMP-Activated Protein Kinase (AMPK) Signaling"],"prefix":"10.3390","volume":"15","author":[{"given":"Jian-Li","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Respiration, the First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, the First People's Hospital of Hangzhou, Hangzhou 310003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, the First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2014,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1161\/01.CIR.87.5.1776","article-title":"Diagnosis and therapy of Kawasaki disease in children","volume":"87","author":"Dajani","year":"1993","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1542\/peds.63.2.175","article-title":"Kawasaki disease: Effect of treatment on coronary artery involvement","volume":"63","author":"Kato","year":"1979","journal-title":"Pediatrics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1097\/00006454-199408000-00005","article-title":"Seven-year national survey of Kawasaki disease and acute rheumatic fever","volume":"13","author":"Taubert","year":"1994","journal-title":"Pediatr. 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