{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T19:23:04Z","timestamp":1783452184262,"version":"3.55.0"},"reference-count":46,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"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":["Phytotherapy Research"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Metabolic dysfunction\u2010associated steatotic liver disease (MASLD) is a prevalent chronic liver disorder with limited treatment and manifests as hepatic lipid accumulation. The reduction of nuclear receptor corepressor 1 (NCoR1) activates the nuclear receptor PPAR\u03b1, which plays a crucial role in alleviating lipid accumulation. We found that Scutellarin (Scu) regulated autophagy\u2010mediated NCoR1\/PPAR\u03b1 to enhance fatty acid (FA) \u03b2\u2010oxidation and peroxisome production, thereby alleviating the lipid accumulation of MASLD. We used palmitic acid (PA)\u2010treated human hepatocellular carcinoma (HepG2) and alpha mouse liver 12 (AML12) cells, as well as high\u2010fat diet\u2010fed C57BL\/6J mice to evaluate the protective effect of Scu on MASLD. Scu reduced the levels of total cholesterol, triglycerides, and lipid droplets, whereas it dose\u2010dependently increased the levels of \u03b2\u2010hydroxybutyrate. In addition, Scu increased mRNA and protein expression of PPAR\u03b1 and promoted the transcriptional activity of FA \u03b2\u2010oxidation\u2010related target genes. In\u00a0vitro, inhibition of PPAR\u03b1 with small interfering RNA (siRNA) abolished the activation of FA \u03b2\u2010oxidation by Scu. Cellular thermal shift assay and drug affinity responsive target stability demonstrated that Scu did not interact directly with PPAR\u03b1. Moreover, Scu increased the protein expression of 70\u2010kDa peroxisomal membrane protein and the mRNA expression of peroxisome biogenesis\u2010related genes. These effects were reversed by PPAR\u03b1\u2010siRNA. Scu improved the impaired autophagy while reducing the mRNA and protein expression of NCoR1. Notably, Scu reduced the colocalization of NCoR1 with PPAR\u03b1 and increased its colocalization with the autophagosome GABARAP. 3\u2010MA, an autophagy inhibitor, attenuated Scu\u2010mediated protective effects by FA \u03b2\u2010oxidation and peroxisome biogenesis both in\u00a0vitro and in\u00a0vivo. In summary, Scu reduces lipid accumulation by improving the impaired autophagy, decreasing NCoR1 expression to activate PPAR\u03b1, thereby simultaneously enhancing FA \u03b2\u2010oxidation and peroxisome biogenesis, ultimately ameliorating hepatic steatosis.<\/jats:p>","DOI":"10.1002\/ptr.70367","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T17:45:22Z","timestamp":1778003122000},"page":"4278-4293","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Scutellarin Alleviates Hepatic Steatosis by Autophagy\u2010Mediated\n                    <scp>NCoR1<\/scp>\n                    \/\n                    <scp>PPAR\u03b1<\/scp>\n                    \u2010Driven Fatty Acid \u03b2\u2010Oxidation and Enhancing Peroxisome Biogenesis"],"prefix":"10.1002","volume":"40","author":[{"given":"Jianmei","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Pharmacology of Chinese 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