{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T15:23:22Z","timestamp":1791818602870,"version":"4.3.4"},"reference-count":32,"publisher":"Wiley","license":[{"start":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T00:00:00Z","timestamp":1749772800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabet Med"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Diabetic foot ulcer (DFU) is a common and serious complication of diabetes mellitus (DM) and one of the main causes of disability or mortality in diabetic patients. Astragaloside IV (AS\u2010IV) is a naturally occurring plant product that can be used to treat DM and its complications. N6\u2010methyladenosine (m6A) modification participates in the progression of DM. This study aimed to explore the potential molecular mechanisms of m6A modification induced by AS\u2010IV treatment of DFU.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The biological behaviours of cells were assessed by cell counting kit\u20108, EdU incorporation, wound healing, and transwell assays. The levels of m6A modification and relative genes mRNA were detected by dot blot assay and quantitative real\u2010time PCR. The interactions between molecules were evaluated by methylated RNA immunoprecipitation (MeRIP), RIP, fluorescence in\u00a0situ hybridisation, and dual\u2010luciferase reporter analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results suggested AS\u2010IV facilitated cell proliferation and migration of AGE\u2010induced HaCaT cells and accelerated wound healing, thereby alleviating DFU progression. Mechanically, AS\u2010IV promoted the m6A modification levels of SIRT1 in\u00a0vivo and in\u00a0vitro which was associated with increased METTL3. Besides, SIRT1 was the target of METTL3\u2010mediated m6A modification. Silencing of SIRT1 abrogated the biological effects of METTL3.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The mitigation effect of AS\u2010IV on DFU is achieved by promoting m6A modification of SIRT1 to enhance SIRT1 stability. This study not only reveals the novel molecular mechanisms of AS\u2010IV in the treatment of DFU but also provides new insights for the treatment of diabetes and its complications.<\/jats:p><\/jats:sec>","DOI":"10.1111\/dme.70087","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T08:05:38Z","timestamp":1749801938000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Astragaloside <scp>IV<\/scp> alleviates diabetic foot ulcers by promoting the <scp>METTL3<\/scp>\u2010mediated <scp>m6A<\/scp> modification of <scp>SIRT1<\/scp>"],"prefix":"10.1111","author":[{"given":"Yu","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Burn and Plastic Surgery Tangshan Gongren Hospital  Tangshan Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Burn and Plastic Surgery 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