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Diabetic neuropathy is one of the prevalent complications of diabetes, which also includes diabetic nephropathy, retinopathy, cardiomyopathy, and diabetic foot diseases. The present study evaluated the protective effects of Ethiopian coffee beans (\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Coffea arabica<\/jats:italic>\n                    <\/jats:styled-content>\n                    ) against glucose\u2010induced brain tissue injury using in\u00a0vitro, ex\u00a0vivo, and in silico experimental models. Oxidative injury was induced by incubating brain tissue collected from normal male Sprague\u2013Dawley rats in glucose solution and treated with the different concentrations of Ethiopian coffee bean extracts (hot and cold aqueous) for 2\u2009h at 37\u00b0C in a 95% O\n                    <jats:sub>2<\/jats:sub>\n                    and 5% CO\n                    <jats:sub>2<\/jats:sub>\n                    incubator. Induction of glucose\u2010mediated (0.0111\u2009M glucose) oxidative injury led to significant depletion of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and total glycogen levels, while elevating malonaldehyde (MDA), nitric oxide (NO), glycogen phosphorylase, fructose\u20101,6\u2010bisphosphatase, ATPase, and acetylcholinesterase (AChE) activity levels. Treatment with different concentrations of the aqueous extracts of coffee beans significantly restored the levels and activities of the biomarkers mentioned above. LC\u2013MS analysis indicates the presence of chlorogenic acid (CGA), caffeic acid, quinic acid, caffeine, Cafestol, Kahweol, ferulic acid, and catechol in the coffee extracts. In silico analysis revealed a strong molecular interaction between CGA and the CAT, SOD, and AChE enzymes. The data from this study suggest that bioactive compounds from\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Coffea arabica<\/jats:italic>\n                    <\/jats:styled-content>\n                    have a potential neuroprotective effect against glucose\u2010mediated oxidative neurodegeneration in rat brain tissue.\n                  <\/jats:p>","DOI":"10.1002\/fsn3.72054","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T10:20:31Z","timestamp":1783506031000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuroprotective Effects of Ethiopian Coffee Beans against Hyperglycemia\u2010induced Brain Injury in Rats"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9918-5409","authenticated-orcid":false,"given":"Almahi I.","family":"Mohamed","sequence":"first","affiliation":[{"name":"Department of Biochemistry, School of Agriculture and Science University of KwaZulu\u2010Natal, Westville Campus  Durban South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kolawole A.","family":"Olofinsan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of the Free State  Bloemfontein South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ochuko L.","family":"Erukainure","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Agriculture and Science University of KwaZulu\u2010Natal, Westville Campus  Durban South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huda","family":"Ismail","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Agriculture and Science University of KwaZulu\u2010Natal, Westville Campus  Durban South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0309-9491","authenticated-orcid":false,"given":"Md. Shahidul","family":"Islam","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Agriculture and Science University of KwaZulu\u2010Natal, Westville Campus  Durban South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9020093"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2014.05.007"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(84)05016-3"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/diabetology2020004"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-020-00583-6"},{"issue":"1","key":"e_1_2_10_7_1","first-page":"330","article-title":"Neuroprotective Effect of Chlorogenic Acids Against Alzheimer's Disease","volume":"6","author":"Anggreani 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