{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T01:03:11Z","timestamp":1783126991959,"version":"3.54.6"},"reference-count":50,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,29]],"date-time":"2024-06-29T00:00:00Z","timestamp":1719619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>This study aimed to investigate a synergistic anti-inflammatory effect of a citrus flavonoid nobiletin and docosahexaenoic acid (DHA), one of n-3 long-chain polyunsaturated fatty acids, in combination. Simultaneous treatment with nobiletin and DHA synergistically inhibited nitric oxide production (combination index &lt; 0.9) by mouse macrophage-like RAW 264.7 cells stimulated with lipopolysaccharide (LPS) without cytotoxicity. On the other hand, the inhibitory effect of nobiletin and DHA in combination on proinflammatory cytokine production was not synergistic. Neither nobiletin nor DHA affected the phagocytotic activity of RAW 264.7 cells stimulated with LPS. Immunoblot analysis revealed that the inhibition potency of DHA on the phosphorylation of ERK and p38 and nuclear translocation of NF-\u03baB is markedly enhanced by simultaneously treating with nobiletin, which may lead to the synergistic anti-inflammatory effect. Overall, our findings show the potential of the synergistic anti-inflammatory effect of nobiletin and DHA in combination.<\/jats:p>","DOI":"10.3390\/nu16132080","type":"journal-article","created":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T04:53:27Z","timestamp":1719809607000},"page":"2080","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Anti-Inflammatory Activity of the Combination of Nobiletin and Docosahexaenoic Acid in Lipopolysaccharide-Stimulated RAW 264.7 Cells: A Potential Synergistic Anti-Inflammatory Effect"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4205-8465","authenticated-orcid":false,"given":"Kosuke","family":"Nishi","sequence":"first","affiliation":[{"name":"Food and Health Function Research Center, Ehime University, Matsuyama 790-8566, Japan"},{"name":"Department of Bioscience, Graduate School of Agriculture, Ehime University, Matsuyama 790-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Nakatani","sequence":"additional","affiliation":[{"name":"Department of Bioscience, Graduate School of Agriculture, Ehime University, Matsuyama 790-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7663-6481","authenticated-orcid":false,"given":"Momoko","family":"Ishida","sequence":"additional","affiliation":[{"name":"Food and Health Function Research Center, Ehime University, Matsuyama 790-8566, Japan"},{"name":"Department of Bioscience, Graduate School of Agriculture, Ehime University, Matsuyama 790-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayumu","family":"Kadota","sequence":"additional","affiliation":[{"name":"Ikata Service Co., Ltd., Ikata 769-0421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Sugahara","sequence":"additional","affiliation":[{"name":"Food and Health Function Research Center, Ehime University, Matsuyama 790-8566, Japan"},{"name":"Department of Bioscience, Graduate School of Agriculture, Ehime University, Matsuyama 790-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e23","DOI":"10.1017\/S1462399411001943","article-title":"Inflammation and wound healing: The role of the macrophage","volume":"13","author":"Koh","year":"2011","journal-title":"Expert Rev. 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