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This study aimed to clarify how nuciferine mitigates hepatic inflammation in NASH by exploring its interactions with immune pathways and gut microbiota. Initially, a NASH mouse model was induced using a methionine\u2010 and choline\u2010deficient diet, with nuciferine administered orally. Furthermore, liver damage was assessed, and hepatic M1 (CD11B\n                    <jats:sup>+<\/jats:sup>\n                    pro\u2010inflammatory) and M2 (CD163\n                    <jats:sup>+<\/jats:sup>\n                    anti\u2010inflammatory) macrophages were quantified. Molecular assays measured SIRT1 gene expression, while miRNA sequencing and dual\u2010luciferase assays explored its role in the SIRT1\/NF\u2010\u03baB pathway. Additionally, gut microbiota were analyzed via 16S rRNA sequencing, and fluorescently labeled\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Akkermansia muciniphila<\/jats:italic>\n                    <\/jats:styled-content>\n                    \u2010derived extracellular vesicles (\n                    <jats:italic>Akk<\/jats:italic>\n                    \u2010EVs) were tracked in\u00a0vivo and in\u00a0vitro. Treatment with nuciferine reduced liver injury, decreasing pro\u2010inflammatory M1 macrophages and increasing anti\u2010inflammatory M2 macrophages. Meanwhile, it upregulated hepatic SIRT1, suppressing miR\u201023a\u20103p to inhibit the NF\u2010\u03baB pathway and promote M1\u2010to\u2010M2 polarization. Gut microbiota analysis showed nuciferine enriched\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Akkermansia muciniphila<\/jats:italic>\n                    <\/jats:styled-content>\n                    , and fluorescent imaging confirmed\n                    <jats:italic>Akk<\/jats:italic>\n                    \u2010EVs entered liver tissues and macrophages, exerting direct anti\u2010inflammatory effects. In conclusion, nuciferine protects against NASH through dual mechanisms: modulating the SIRT1\/NF\u2010\u03baB pathway to reduce hepatic inflammation and enhancing\n                    <jats:italic>Akk\u2010<\/jats:italic>\n                    EVs. These findings highlight its therapeutic potential for NASH, linking host immune responses with gut microbiota interactions.\n                  <\/jats:p>","DOI":"10.1002\/ptr.8528","type":"journal-article","created":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T08:29:07Z","timestamp":1751617747000},"page":"3508-3525","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Nuciferine Exerts Anti\u2010Inflammatory Effects in Mice With Non\u2010Alcoholic Steatohepatitis by Regulating the\n                    <scp>miR<\/scp>\n                    \u201023a\u20103p\u2010\n                    <scp>SIRT1<\/scp>\n                    \u2010\n                    <scp>NF<\/scp>\n                    \u2010\n                    <scp>\u03baB<\/scp>\n                    Pathway and\n                    <scp>\n                      <i>Akkermansia muciniphila<\/i>\n                    <\/scp>\n                    \u2010Extracellular 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