{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T10:40:44Z","timestamp":1787222444180,"version":"build-2736575974"},"reference-count":43,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T00:00:00Z","timestamp":1752796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea","award":["2016R1D1A3B02006754"],"award-info":[{"award-number":["2016R1D1A3B02006754"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Natural products are key sources of anti-inflammatory agents, yet the potential of fish visceral extracts remains largely unexplored. This study evaluated the anti-inflammatory activity of a spleen extract from rainbow trout (Oncorhynchus mykiss). Methods: A crude spleen extract and its four solvent fractions were tested in LPS-stimulated RAW264.7 macrophages. Nitric oxide production and expression of iNOS, COX-2, and cytokines were assessed by qRT-PCR and Western blotting. The most active fraction, OSB (n-butanol layer), was further analyzed for its effects on NF-\u03baB signaling, macrophage polarization, and ROS generation. Results: The crude spleen extract significantly reduced NO production and downregulated iNOS and COX-2 expression at both the transcriptional and translational levels. Among the four fractions, the OSB fraction exhibited the most potent and consistent anti-inflammatory effects. OSB markedly suppressed LPS-induced expression of iNOS, COX-2, and pro-inflammatory cytokines, while enhancing anti-inflammatory cytokines. Mechanistic analyses demonstrated that OSB inhibited NF-\u03baB activation by preventing the nuclear translocation of the p65 subunit. Additionally, OSB attenuated LPS-induced ROS production and reduced the expression of M1 macrophage markers, indicating inhibition of M1 polarization. Conclusions: The OSB fraction from rainbow trout spleen exhibits potent anti-inflammatory activity by modulating the NF-\u03baB pathway and suppressing M1 macrophage polarization, suggesting its potential as a natural therapeutic agent.<\/jats:p>","DOI":"10.3390\/genes16070837","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T12:09:53Z","timestamp":1752840593000},"page":"837","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Rainbow Trout (Oncorhynchus mykiss) Spleen-Derived Bioactive Compounds Suppress Pro-Inflammatory Gene Networks via NF-\u03baB Pathway Modulation"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-3810-389X","authenticated-orcid":false,"given":"Do-Yeon","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2305-4072","authenticated-orcid":false,"given":"Woo-Sung","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3060-6107","authenticated-orcid":false,"given":"Ju-Hee","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3273-0596","authenticated-orcid":false,"given":"Seoghyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1070-7602","authenticated-orcid":false,"given":"Jinyoung","family":"Park","sequence":"additional","affiliation":[{"name":"Laboratory of Natural Products Chemistry, College of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0072-8720","authenticated-orcid":false,"given":"Woohyun","family":"Song","sequence":"additional","affiliation":[{"name":"Laboratory of Natural Products Chemistry, College of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5986-9024","authenticated-orcid":false,"given":"Heejung","family":"Yang","sequence":"additional","affiliation":[{"name":"Laboratory of Natural Products Chemistry, College of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3753-3129","authenticated-orcid":false,"given":"Han-Heom","family":"Na","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3047-0380","authenticated-orcid":false,"given":"Keun-Cheol","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/nri3561","article-title":"Concepts of tissue injury and cell death in inflammation: A historical perspective","volume":"14","author":"Wallach","year":"2014","journal-title":"Nat. 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