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The mice received thioacetamide (TAA) (150 mg\/kg, biweekly) via intraperitoneal (i.p.) injection for nine consecutive weeks to induce liver fibrosis. SEMA was administered orally once daily at a dose of 0.12 mg\/kg.  Administration of SEMA improved liver function as demonstrated by the reduction in the plasma levels of aminotransferases and gamma-glutamyl transpeptidase (GGT) along with the rise in serum albumin level. Moreover, SEMA mitigated the TAA-induced histopathological changes and reduced the content of \u03b1-smooth muscle actin (\u03b1-SMA). SEMA ameliorated the TAA-induced oxidative stress by mitigating the derangement in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, reducing glutathione (GSH) levels, and decreasing malondialdehyde (MDA) levels. The hepatic TGF-\u03b2\/Smad\u00a0signaling pathway\u00a0was downregulated by SEMA treatment, while sirtuin 1 (SIRT1) content and phosphorylated AMP-activated protein kinase (p-AMPK) expression were upregulated. SEMA significantly reduced the severity of liver fibrosis induced by TAA through SIRT1 activation. And it holds promise as a therapeutic agent for liver fibrosis.<\/jats:p>","DOI":"10.1007\/s00210-025-04675-x","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:25:32Z","timestamp":1760919932000},"page":"4413-4425","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Repurposing of semaglutide by targeting SIRT1 and TGF\u2010\u03b2\/Smad signaling in hepatic fibrosis"],"prefix":"10.1007","volume":"399","author":[{"given":"Omnia A.","family":"Hawary","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walaa","family":"Wadie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmin A. 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