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For in vivo study, Type 2 Diabetes Mellitus (T2DM) was induced in rats by feeding a HFD for 3 weeks, followed by a single intraperitoneal dose of STZ on day 21. Animals were divided into 4 groups: I \u2013 Control, II \u2013 T2DM, III \u2013 T2DM plus Met (250\u00a0mg\/kg) and IV \u2013 T2DM plus BFE (200\u00a0mg\/kg). After STZ administration, the animals underwent a glucose tolerance test. Biochemical and molecular analyses were performed in serum and brain tissues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>BFE and Met improved diabetic parameters, mitigating hyperglycemia, dyslipidemia, and inflammation by lowering serum glucose, total cholesterol, triglycerides, very low-density lipoprotein, interleukin-6, adenosine deaminase activity, and reactive species levels, while restoring high-density lipoprotein and paraoxonase-1 activity in blood. Both treatments reduced oxidative stress in the cerebral cortex by lowering reactive species, nitrite, and thiobarbituric acid reactive substances levels and increasing sulfhydryl groups, superoxide dismutase and catalase activity. Also, BFE upregulated phosphatidylinositol 3-kinase, insulin receptor substrate-1, forkhead box O-3a in the cerebral cortex.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings highlight the potential of BFE as a promising natural therapeutic agent for T2DM management, demonstrating efficacy comparable to Met in addressing metabolic and oxidative impairments.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11033-026-11735-9","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T06:11:48Z","timestamp":1775196708000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulatory role of blackberry fruit standardized extract on brain redox status and insulin signaling in type 2 diabetic rats"],"prefix":"10.1007","volume":"53","author":[{"given":"Imtiaz","family":"Ahmad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia Eisenhardt","family":"de Mello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa Menezes","family":"da Silveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayara Sandrielly Soares","family":"de Aguiar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcia","family":"Vizzotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William Borges","family":"Domingues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Petitemberte","family":"de Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinicius Farias","family":"Campos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rejane Giacomelli","family":"Tavares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roselia Maria","family":"Spanevello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francieli Moro","family":"Stefanello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,3]]},"reference":[{"key":"11735_CR1","doi-asserted-by":"publisher","first-page":"1161521","DOI":"10.3389\/fendo.2023.1161521","volume":"14","author":"R Ruze","year":"2023","unstructured":"Ruze R, Li T, Zou X, Song J, Chen Y, Xu R, Yin X, Xu Q (2023) Obesity and type 2 diabetes mellitus: connections in epidemiology, pathogenesis, and treatments. 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