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This study aimed to investigate the potential therapeutic effects of cranberry extract (<jats:italic>Vaccinium macrocarpon<\/jats:italic>) and metformin on metabolic syndrome in a rat model. Forty rats were divided into the following groups: normal control, MetS (high fat and fructose for 4 weeks followed by streptozotocin 35\u00a0mg\/kg, i.p.), MetS\u2009+\u2009cranberry (50\u00a0mg\/kg), MetS\u2009+\u2009cranberry (100\u00a0mg\/kg), and MetS\u2009+\u2009metformin (200\u00a0mg\/kg) groups. Treatments were given orally for four weeks with the continuation of a high-fat and high-fructose diet. The evaluations included key metabolic parameters, liver and kidney pathology, and relevant molecular pathways. The present results revealed that MetS induction significantly increased body weight, BMI, fasting glucose, and OGTT results; impaired lipid profile, creatinine and blood pressure; and upregulated hepatic gene expression of Rho-associated protein kinase 1 (<jats:italic>Rock1<\/jats:italic> ) and sterol regulatory element-binding transcription factor 1 (<jats:italic>Srebf1<\/jats:italic>), which encodes the protein SREBP-1c. In addition to hepatic and renal structural abnormalities, increased collagen and increased iNOS\/TGF-\u03b21 immunoreactivity were observed. Cranberry ameliorated metabolic parameters in a dose-dependent manner, upregulated adenosine monophosphate-activated protein kinase (AMPK), downregulated <jats:italic>Rock1<\/jats:italic> and Srebf1 expression, improved the histopathology of the liver and kidney and decreased the immunoexpression of iNOS and TGF-\u03b21. The results for cranberry were generally comparable to those for metformin. In conclusion, cranberry extract is potentially a safe therapeutic strategy for MetS, offering broad-spectrum action, organ protection, and molecular pathway modulation. These findings strongly support cranberry as a promising natural approach for managing MetS.<\/jats:p>","DOI":"10.1038\/s41598-025-16925-2","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T12:38:32Z","timestamp":1757939912000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Cranberry improves metabolic syndrome-related organ dysfunction in rats by modulating AMPK\/SREBP1, ROCK1 and TGF-\u03b21"],"prefix":"10.1038","volume":"15","author":[{"given":"Sahar M.","family":"Elashmony","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosra","family":"Alhindi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina H.","family":"Merzeban","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rehab A.","family":"Mohammed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmaa Mohamed","family":"Elsayed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa A.","family":"Sofi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rania H.","family":"Mahmoud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanan A.","family":"Shamardl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina Elsayed","family":"Shaker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,15]]},"reference":[{"key":"16925_CR1","doi-asserted-by":"crossref","unstructured":"Bruce, K. 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