{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T14:17:03Z","timestamp":1780496223508,"version":"3.54.1"},"reference-count":41,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T00:00:00Z","timestamp":1753401600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T00:00:00Z","timestamp":1753401600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp;amp; Biodiversity"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Sakuranin (SKR) is naturally occurring compound known for its anti\u2010inflammatory and antioxidant activities; however, its precise molecular mechanisms in modulating inflammation through toll\u2010like receptor 4 (TLR4) signaling remain unclear. This study investigates the anti\u2010inflammatory effects of SKR in lipopolysaccharide (LPS)\u2010stimulated RAW 264.7 macrophages and zebrafish larvae, focusing on the TLR4\u2013nuclear factor\u2010kappa B (NF\u2010\u03baB) signaling pathway. SKR significantly inhibited the production of nitric oxide (NO), prostaglandin E\n                    <jats:sub>2<\/jats:sub>\n                    (PGE\n                    <jats:sub>2<\/jats:sub>\n                    ), interleukin\u201012 (IL\u201012), and tumor necrosis factor\u2010alpha (TNF\u2010\u03b1), while downregulating the expression of inducible NO synthase (NOS2) and cyclooxygenase\u20102 (COX2) at both transcriptional and translational levels. In vivo, SKR reduced LPS\u2010induced mortality, restored cardiac function, and attenuated immune cell infiltration in zebrafish larvae, further underscoring its systemic anti\u2010inflammatory effects. Mechanistic studies revealed that SKR inhibited NF\u2010\u03baB nuclear translocation and directly interacted with the TLR4\/myeloid differentiation factor 2 (MD2) complex, thereby disrupting LPS\u2013TLR4 signaling. Molecular docking and colocalization analyses confirmed that SKR directly binds TLR4, potentially interfering with LPS recognition and downstream pro\u2010inflammatory signaling activation. Collectively, these findings highlight SKR as a potent modulator of TLR4\u2010mediated inflammation, offering promising therapeutic potential for inflammatory disorders. Further investigations into its pharmacokinetics, bioavailability, and long\u2010term efficacy in chronic inflammatory conditions are warranted to support its clinical applications.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.202501167","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T18:45:12Z","timestamp":1753469112000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Sakuranin Is a Novel Anti\u2010Inflammatory Agent Targeting TLR4\u2013NF\u2010\u03baB Signaling Pathways"],"prefix":"10.1002","volume":"22","author":[{"given":"Jayasingha Arachchige Chathuranga Chanaka","family":"Jayasingha","sequence":"first","affiliation":[{"name":"Department of Marine Life Science Jeju National University  Jeju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoung Tae","family":"Lee","sequence":"additional","affiliation":[{"name":"Forest Microbiology 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