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Transforming growth factor beta-1 (TGF-\u03b21), via Smad2\/3 signaling pathway, promotes fibrotic gene expression. Oleuropein (OL), a major phenolic constituent of olive products, exhibits significant antioxidant properties and contributes to cardiovascular protection. This study aimed to investigate the anti-fibrotic effects of OL in a rat model of DCM and its modulation of the TGF-\u03b21\/Smad signaling pathway, using Losartan as a positive control. Thirty-two male Wistar rats were randomly assigned to four groups: control, DCM, DCM\u2009+\u2009OL (40 mg\/kg), and DCM\u2009+\u2009Losartan (10 mg\/kg). DCM was induced via high-fat diet (HFD) and a single low-dose streptozotocin (STZ) injection (40 mg\/kg). Cardiac function was assessed by echocardiography. Histological evaluation included hematoxylin\u2013eosin (H&amp;E) and Masson trichrome staining. Cardiac biomarkers, oxidative stress markers, and fibrosis-related markers were analyzed using RT-qPCR, immunohistochemistry, and western blotting. DCM rats exhibited cardiac dysfunction and fibrosis. OL treatment significantly improved cardiac function, reduced collagen and fibronectin (FN) deposition, and downregulated TGF-\u03b21, Smad2\/3, \u03b1-smooth muscle actin (\u03b1-SMA), collagen types I\/III, matrix metalloproteinases-2\/9 (MMPs), and tissue inhibitor of metalloproteinases-1 (TIMP-1), while enhancing Smad7 expression. Besides, OL demonstrated notable antioxidant and antidiabetic effects. In conclusion, OL alleviates cardiac fibrosis and dysfunction in DCM, potentially through modulation of the TGF-\u03b21\/Smad signaling, highlighting its therapeutic promise in diabetic cardiac complications.<\/jats:p>","DOI":"10.1038\/s41598-026-49571-3","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T21:14:42Z","timestamp":1779138882000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oleuropein attenuates cardiac fibrosis via modulation of TGF-\u03b21\/Smad pathway in diabetic cardiomyopathy rat model"],"prefix":"10.1038","volume":"16","author":[{"given":"Lobna M.","family":"Abdelrauf","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danira A.","family":"Habashy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadia M.","family":"Sharaf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asmaa A.","family":"El-Shafei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lobna","family":"Kassem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ragwa M.","family":"Abdelghany","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"49571_CR1","doi-asserted-by":"publisher","first-page":"2155","DOI":"10.1016\/j.biopha.2018.11.086","volume":"109","author":"AM Al Hroob","year":"2019","unstructured":"Al Hroob, A. 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