{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T09:50:39Z","timestamp":1791366639815,"version":"4.3.1"},"reference-count":48,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"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":["Diabet Med"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Metabolic\u2010associated fatty liver disease (MAFLD), particularly advanced metabolic dysfunction\u2010associated steatohepatitis (MASH), leads to irreversible liver damage. Specnuezhenide (SPE), naturally isolated from\n                      <jats:italic>Ligustrum lucidum Ait,<\/jats:italic>\n                      has been demonstrated to exert hepatoprotective effects. However, its functional role and underlying mechanisms in MAFLD remain poorly understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>This study investigated the therapeutic effects and potential mechanism of SPE on MAFLD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>MAFLD mice induced by high\u2010fat diet (HFD) were employed to assess SPE's therapeutic effects in\u00a0vivo. The impact of SPE on gut microbiota was analysed by 16S rRNA sequencing. RNA\u2010seq analysis was conducted to uncover SPE's molecular mechanisms. Complementary in\u00a0vitro investigations utilized FFA\u2010treated HepG2 cells to systematically examine SPE's cellular\u2010level impacts and regulatory pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The results indicated that SPE could improve hepatic steatosis, liver injury and oxidative stress in MAFLD mice. SPE treatment also affected the diversity of gut microbiota and altered their composition by decreasing the Firmicutes\/Bacteroidetes (F\/B) ratio. The results of 16S rRNA sequencing, RNA\u2010seq and Western blot analysis indicated that the effect of SPE on MAFLD was related to fatty acid beta\u2010oxidation and the PPAR\u03b1 signalling pathway. Moreover, in HepG2 cells, SPE reduced FFA\u2010induced lipid accumulation and oxidative stress, which was dependent on PPAR\u03b1 up\u2010regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This is the first study to demonstrate that SPE alleviates MAFLD and is associated with modulation of gut microbiota composition and activation of the PPAR\u03b1 signalling pathway. Our findings suggest a potential link between gut microbiota remodelling and PPAR\u03b1\u2010mediated fatty acid oxidation, highlighting its potential as a therapeutic candidate for MAFLD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dme.70362","type":"journal-article","created":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T05:14:52Z","timestamp":1778908492000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Ligustrum lucidum\u2010derived glycoside specnuezhenide alleviates metabolic\u2010associated fatty liver disease in mice via modulation of gut microbiota and the\n                    <scp>PPAR\u03b1<\/scp>\n                    signalling pathway"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2317-2019","authenticated-orcid":false,"given":"Kai","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Pharmacy Xijing Hospital, Fourth 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