{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T18:21:17Z","timestamp":1783621277116,"version":"3.55.0"},"reference-count":75,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Metab Brain Dis"],"DOI":"10.1007\/s11011-026-01925-6","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T05:16:09Z","timestamp":1783574169000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Polydatin inhibits hippocampal neurodegeneration in diabetic rats via modulation of oxidative stress and NF-kB\/COX-2\/IL-6 inflammatory pathway"],"prefix":"10.1007","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0876-0090","authenticated-orcid":false,"given":"Ahmed I.","family":"Yousef","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanaa M. Abd","family":"El-Twab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally M.","family":"Khadrawy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adel","family":"Abdel-Moneim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rehab G.","family":"Khalil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"1925_CR1","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1139\/bcb-2014-0122","volume":"93","author":"MM Abdel-Daim","year":"2015","unstructured":"Abdel-Daim MM, Abd Eldaim MA, Hassan AGA (2015) Trigonella foenum-graecum ameliorates acrylamide-induced toxicity in rats: Roles of oxidative stress, proinflammatory cytokines, and DNA damage. Biochem Cell Biol 93:192\u2013198. https:\/\/doi.org\/10.1139\/bcb-2014-0122","journal-title":"Biochem Cell Biol"},{"key":"1925_CR3","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1007\/s11011-017-0039-8","volume":"32","author":"A Abdel-Moneim","year":"2017","unstructured":"Abdel-Moneim A, Yousef AI, Abd El-Twab SM et al (2017) Gallic acid and p-coumaric acid attenuate type 2 diabetes-induced neurodegeneration in rats. Metab Brain Dis 32:1279\u20131286. https:\/\/doi.org\/10.1007\/s11011-017-0039-8","journal-title":"Metab Brain Dis"},{"key":"1925_CR2","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1080\/13813455.2020.1762659","volume":"128","author":"A Abdel-Moneim","year":"2022","unstructured":"Abdel-Moneim A, Abd El-Twab SM, Yousef AI et al (2022) New insights into the in vitro, in situ and in vivo antihyperglycemic mechanisms of gallic acid and p-coumaric acid. Arch Physiol Biochem 128:1188\u20131194. https:\/\/doi.org\/10.1080\/13813455.2020.1762659","journal-title":"Arch Physiol Biochem"},{"key":"1925_CR4","doi-asserted-by":"publisher","first-page":"13398","DOI":"10.1038\/s41598-023-40160-2","volume":"13","author":"PC Agu","year":"2023","unstructured":"Agu PC, Afiukwa CA, Orji OU et al (2023) Molecular docking as a tool for the discovery of molecular targets of nutraceuticals in diseases management. Sci Rep 13:13398","journal-title":"Sci Rep"},{"key":"1925_CR5","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1002\/cbf.1006","volume":"21","author":"N Aksoy","year":"2003","unstructured":"Aksoy N, Vural H, Sabuncu T, Aksoy S (2003) Effects of melatonin on oxidative\u2013antioxidative status of tissues in streptozotocin-induced diabetic rats. Cell Biochem Function 21:121\u2013125. https:\/\/doi.org\/10.1002\/cbf.1006","journal-title":"Cell Biochem Function"},{"key":"1925_CR6","doi-asserted-by":"publisher","first-page":"2214","DOI":"10.1093\/bioinformatics\/btv082","volume":"31","author":"A Alhossary","year":"2015","unstructured":"Alhossary A, Handoko SD, Mu Y, Kwoh C-K (2015) Fast, accurate, and reliable molecular docking with QuickVina 2. Bioinformatics 31:2214\u20132216","journal-title":"Bioinformatics"},{"key":"1925_CR7","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1006\/jmbi.1997.1245","volume":"272","author":"A Alvarez","year":"1997","unstructured":"Alvarez A, Opazo C, Alarc\u00f3n R et al (1997) Acetylcholinesterase promotes the aggregation of amyloid-\u03b2-peptide fragments by forming a complex with the growing fibrils. J Mol Biol 272:348\u2013361","journal-title":"J Mol Biol"},{"key":"1925_CR8","doi-asserted-by":"publisher","first-page":"4132","DOI":"10.1212\/WNL.0000000000211472","volume":"104","author":"MA Arshad","year":"2025","unstructured":"Arshad MA, Koppanatham A, Zulfiqar K et al (2025) Hypertension and diabetes as risk factors for Alzheimer\u2019s disease-related mortality, a retrospective epidemiological study (P11-3.018). Neurology 104:4132. https:\/\/doi.org\/10.1212\/WNL.0000000000211472","journal-title":"Neurology"},{"key":"1925_CR9","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1001\/archneur.61.5.661","volume":"61","author":"Z Arvanitakis","year":"2004","unstructured":"Arvanitakis Z, Wilson RS, Bienias JL et al (2004) Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. Arch Neurol 61:661\u2013666","journal-title":"Arch Neurol"},{"key":"1925_CR10","doi-asserted-by":"publisher","first-page":"1452989","DOI":"10.3389\/fphar.2024.1452989","volume":"15","author":"FS Bagheri Bavandpouri","year":"2024","unstructured":"Bagheri Bavandpouri FS, Azizi A, Abbaszadeh F et al (2024) Polydatin attenuated neuropathic pain and motor dysfunction following spinal cord injury in rats by employing its anti-inflammatory and antioxidant effects. Front Pharmacol 15:1452989","journal-title":"Front Pharmacol"},{"key":"1925_CR11","doi-asserted-by":"publisher","first-page":"32","DOI":"10.2174\/1567205012666141218140953","volume":"12","author":"R Baranello","year":"2015","unstructured":"Baranello R, Bharani K, Padmaraju V et al (2015) Amyloid-beta protein clearance and degradation (ABCD) pathways and their role in Alzheimer\u2019s Disease. CAR 12:32\u201346. https:\/\/doi.org\/10.2174\/1567205012666141218140953","journal-title":"CAR"},{"key":"1925_CR12","first-page":"2130","volume":"164","author":"H Beck-Nielsen","year":"2002","unstructured":"Beck-Nielsen H (2002) Insulin resistance: organ manifestations and cellular mechanisms. Ugeskr Laeger 164:2130\u20132135","journal-title":"Ugeskr Laeger"},{"key":"1925_CR13","doi-asserted-by":"publisher","first-page":"1563","DOI":"10.1007\/s10571-020-00923-1","volume":"41","author":"P Bheereddy","year":"2021","unstructured":"Bheereddy P, Yerra VG, Kalvala AK et al (2021) SIRT1 activation by polydatin alleviates oxidative damage and elevates mitochondrial biogenesis in experimental diabetic neuropathy. Cell Mol Neurobiol 41:1563\u20131577. https:\/\/doi.org\/10.1007\/s10571-020-00923-1","journal-title":"Cell Mol Neurobiol"},{"key":"1925_CR14","doi-asserted-by":"publisher","first-page":"100936","DOI":"10.1016\/j.arr.2019.100936","volume":"54","author":"V Boccardi","year":"2019","unstructured":"Boccardi V, Murasecco I, Mecocci P (2019) Diabetes drugs in the fight against Alzheimer\u2019s disease. Ageing Res Rev 54:100936","journal-title":"Ageing Res Rev"},{"key":"1925_CR15","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.ejphar.2004.02.053","volume":"490","author":"AM Brands","year":"2004","unstructured":"Brands AM, Kessels RP, de Haan EH et al (2004) Cerebral dysfunction in type 1 diabetes: effects of insulin, vascular risk factors and blood-glucose levels. Eur J Pharmacol 490:159\u2013168","journal-title":"Eur J Pharmacol"},{"key":"1925_CR16","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/S0197-4580(99)00110-4","volume":"21","author":"MM Breteler","year":"2000","unstructured":"Breteler MM (2000) Vascular risk factors for Alzheimer\u2019s disease:: An epidemiologic perspective. Neurobiol Aging 21:153\u2013160","journal-title":"Neurobiol Aging"},{"key":"1925_CR17","doi-asserted-by":"publisher","first-page":"334","DOI":"10.3389\/fphar.2017.00334","volume":"8","author":"Q Chen","year":"2017","unstructured":"Chen Q, Mo R, Wu N et al (2017) Berberine ameliorates diabetes-associated cognitive decline through modulation of aberrant inflammation response and insulin signaling pathway in DM rats. Front Pharmacol 8:334","journal-title":"Front Pharmacol"},{"key":"1925_CR18","doi-asserted-by":"publisher","first-page":"2543","DOI":"10.1002\/jps.20744","volume":"95","author":"YH Choi","year":"2006","unstructured":"Choi YH, Kim SG, Lee MG (2006) Dose-independent pharmacokinetics of metformin in rats: hepatic and gastrointestinal first-pass effects. J Pharm Sci 95:2543\u20132552. https:\/\/doi.org\/10.1002\/jps.20744","journal-title":"J Pharm Sci"},{"key":"1925_CR19","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1097\/00019442-200307000-00003","volume":"11","author":"SE Cook","year":"2003","unstructured":"Cook SE, Miyahara S, Bacanu S-A et al (2003) Psychotic symptoms in Alzheimer disease: evidence for subtypes. Am J geriatric psychiatry 11:406\u2013413","journal-title":"Am J geriatric psychiatry"},{"key":"1925_CR20","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1016\/j.bcp.2008.12.006","volume":"77","author":"CM Cordes","year":"2009","unstructured":"Cordes CM, Bennett RG, Siford GL, Hamel FG (2009) Nitric oxide inhibits insulin-degrading enzyme activity and function through S-nitrosylation. Biochem Pharmacol 77:1064\u20131073","journal-title":"Biochem Pharmacol"},{"key":"1925_CR21","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/S1474-4422(04)00681-7","volume":"3","author":"S Craft","year":"2004","unstructured":"Craft S, Watson GS (2004) Insulin and neurodegenerative disease: shared and specific mechanisms. Lancet Neurol 3:169\u2013178","journal-title":"Lancet Neurol"},{"key":"1925_CR22","doi-asserted-by":"publisher","first-page":"35","DOI":"10.2174\/156720512799015037","volume":"9","author":"S De La Monte","year":"2012","unstructured":"De La Monte S (2012) Brain insulin resistance and deficiency as therapeutic targets in Alzheimers Disease. CAR 9:35\u201366. https:\/\/doi.org\/10.2174\/156720512799015037","journal-title":"CAR"},{"key":"1925_CR23","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1111\/jnc.15166","volume":"156","author":"J Diniz Pereira","year":"2021","unstructured":"Diniz Pereira J, Gomes Fraga V, Morais Santos AL et al (2021) Alzheimer\u2019s disease and type 2 diabetes mellitus: A systematic review of proteomic studies. J Neurochem 156:753\u2013776. https:\/\/doi.org\/10.1111\/jnc.15166","journal-title":"J Neurochem"},{"key":"1925_CR24","doi-asserted-by":"publisher","first-page":"22","DOI":"10.3389\/fncel.2014.00022","volume":"8","author":"NB El Khoury","year":"2014","unstructured":"El Khoury NB, Gratuze M, Papon M-A et al (2014) Insulin dysfunction and Tau pathology. Front Cell Neurosci 8:22","journal-title":"Front Cell Neurosci"},{"key":"1925_CR25","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1055\/s-0035-1559607","volume":"123","author":"L Fei","year":"2015","unstructured":"Fei L, Yong-Jun H, Zhang-Min M et al (2015) Rosiglitazone attenuates memory impairment in aged rat with diabetes by inhibiting NF-kappa B signal pathway activation. Exp Clin Endocrinol Diabetes 123:536\u2013542. https:\/\/doi.org\/10.1055\/s-0035-1559607","journal-title":"Exp Clin Endocrinol Diabetes"},{"key":"1925_CR26","doi-asserted-by":"publisher","first-page":"3644","DOI":"10.2174\/138161209789271799","volume":"15","author":"A Fernandez-Gamba","year":"2009","unstructured":"Fernandez-Gamba A, Leal M, Morelli L, Castano E (2009) Insulin-degrading enzyme: structure-function relationship and its possible roles in health and disease. CPD 15:3644\u20133655. https:\/\/doi.org\/10.2174\/138161209789271799","journal-title":"CPD"},{"key":"1925_CR27","first-page":"100154","volume":"11","author":"K Gajendra","year":"2024","unstructured":"Gajendra K, Pratap GK, Poornima DV et al (2024) Natural acetylcholinesterase inhibitors: a multi-targeted therapeutic potential in Alzheimer\u2019s disease. Eur J Med Chem Rep 11:100154","journal-title":"Eur J Med Chem Rep"},{"key":"1925_CR28","doi-asserted-by":"publisher","first-page":"5481","DOI":"10.3892\/mmr.2016.5936","volume":"14","author":"Y Gao","year":"2016","unstructured":"Gao Y, Chen T, Lei X et al (2016) Neuroprotective effects of polydatin against mitochondrial-dependent apoptosis in the rat cerebral cortex following ischemia\/reperfusion injury. Mol Med Rep 14:5481\u20135488. https:\/\/doi.org\/10.3892\/mmr.2016.5936","journal-title":"Mol Med Rep"},{"key":"1925_CR29","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1002\/(SICI)1096-987X","volume":"17","author":"TA Halgren","year":"1996","unstructured":"Halgren TA (1996) Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94. J Comput Chem 17:490\u2013519. https:\/\/doi.org\/10.1002\/(SICI)1096-987X(199604)17:5\/6%253C490::AID-JCC1%253E3.0.CO;2-P","journal-title":"J Comput Chem"},{"key":"1925_CR30","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/1758-2946-4-17","volume":"4","author":"MD Hanwell","year":"2012","unstructured":"Hanwell MD, Curtis DE, Lonie DC et al (2012) Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J Cheminform 4:17. https:\/\/doi.org\/10.1186\/1758-2946-4-17","journal-title":"J Cheminform"},{"key":"1925_CR31","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.ejphar.2014.09.047","volume":"745","author":"J Hao","year":"2014","unstructured":"Hao J, Chen C, Huang K et al (2014) Polydatin improves glucose and lipid metabolism in experimental diabetes through activating the Akt signaling pathway. Eur J Pharmacol 745:152\u2013165","journal-title":"Eur J Pharmacol"},{"key":"1925_CR32","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1126\/science.290.5489.150","volume":"290","author":"L Hong","year":"2000","unstructured":"Hong L, Koelsch G, Lin X et al (2000) Structure of the protease domain of memapsin 2 (\u03b2-Secretase) complexed with inhibitor. Science 290:150\u2013153. https:\/\/doi.org\/10.1126\/science.290.5489.150","journal-title":"Science"},{"key":"1925_CR33","doi-asserted-by":"publisher","first-page":"7953850","DOI":"10.1155\/2017\/7953850","volume":"2017","author":"Q-H Huang","year":"2017","unstructured":"Huang Q-H, Xu L-Q, Liu Y-H et al (2017) Polydatin protects rat liver against ethanol-induced injury: involvement of CYP2E1\/ROS\/Nrf2 and TLR4\/NF\u2010\u03baB p65 pathway. Evidence-Based Complement Altern Med 2017:7953850. https:\/\/doi.org\/10.1155\/2017\/7953850","journal-title":"Evidence-Based Complement Altern Med"},{"key":"1925_CR34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2014\/491571","volume":"2014","author":"I Jafari Anarkooli","year":"2014","unstructured":"Jafari Anarkooli I, Barzegar Ganji H, Pourheidar M (2014) The protective effects of insulin and natural honey against hippocampal cell death in streptozotocin-induced diabetic rats. J Diabetes Res 2014:1\u20138. https:\/\/doi.org\/10.1155\/2014\/491571","journal-title":"J Diabetes Res"},{"key":"1925_CR35","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.brainresbull.2011.09.021","volume":"87","author":"H Ji","year":"2012","unstructured":"Ji H, Zhang X, Du Y et al (2012) Polydatin modulates inflammation by decreasing NF-\u03baB activation and oxidative stress by increasing Gli1, Ptch1, SOD1 expression and ameliorates blood\u2013brain barrier permeability for its neuroprotective effect in pMCAO rat brain. Brain Res Bull 87:50\u201359","journal-title":"Brain Res Bull"},{"key":"1925_CR36","doi-asserted-by":"publisher","first-page":"1995","DOI":"10.4103\/1673-5374.239448","volume":"13","author":"L Jin","year":"2018","unstructured":"Jin L, Li Y-P, Feng Q et al (2018) Cognitive deficits and Alzheimer-like neuropathological impairments during adolescence in a rat model of type 2 diabetes mellitus. Neural Regeneration Res 13:1995\u20132004","journal-title":"Neural Regeneration Res"},{"key":"1925_CR37","doi-asserted-by":"publisher","first-page":"217","DOI":"10.2174\/138161206775193127","volume":"12","author":"G Johnson","year":"2006","unstructured":"Johnson G, Moore S (2006) The peripheral anionic site of acetylcholinesterase: structure, functions and potential role in rational drug design. CPD 12:217\u2013225. https:\/\/doi.org\/10.2174\/138161206775193127","journal-title":"CPD"},{"key":"1925_CR38","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","volume":"596","author":"J Jumper","year":"2021","unstructured":"Jumper J, Evans R, Pritzel A et al (2021) Highly accurate protein structure prediction with AlphaFold. Nature 596:583\u2013589","journal-title":"Nature"},{"key":"1925_CR39","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1007\/s10753-011-9310-z","volume":"35","author":"G Lanzilli","year":"2012","unstructured":"Lanzilli G, Cottarelli A, Nicotera G et al (2012) Anti-inflammatory effect of resveratrol and polydatin by in vitro IL-17 modulation. Inflammation 35:240\u2013248. https:\/\/doi.org\/10.1007\/s10753-011-9310-z","journal-title":"Inflammation"},{"key":"1925_CR41","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1016\/j.phymed.2012.03.002","volume":"19","author":"R-P Li","year":"2012","unstructured":"Li R-P, Wang Z-Z, Sun M-X et al (2012) Polydatin protects learning and memory impairments in a rat model of vascular dementia. Phytomedicine 19:677\u2013681","journal-title":"Phytomedicine"},{"key":"1925_CR40","doi-asserted-by":"publisher","first-page":"4416","DOI":"10.1039\/C9FO02602A","volume":"11","author":"C-W Li","year":"2020","unstructured":"Li C-W, Deng M-Z, Gao Z-J et al (2020) Effects of compound K, a metabolite of ginsenosides, on memory and cognitive dysfunction in db\/db mice involve the inhibition of ER stress and the NLRP3 inflammasome pathway. Food Funct 11:4416\u20134427","journal-title":"Food Funct"},{"key":"1925_CR42","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1186\/s12974-022-02451-9","volume":"19","author":"S Li","year":"2022","unstructured":"Li S, Li L, Li J et al (2022) miR-203, fine-tunning neuroinflammation by juggling different components of NF-\u03baB signaling. J Neuroinflammation 19:84. https:\/\/doi.org\/10.1186\/s12974-022-02451-9","journal-title":"J Neuroinflammation"},{"key":"1925_CR43","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1016\/S1875-5364(16)30098-X","volume":"14","author":"LY Li YueBi","year":"2016","unstructured":"Li YueBi LY, Zhang WeiHua ZW, Liu HuaDong LH et al (2016) Protective effects of Huanglian Wendan decoction against cognitive deficits and neuronal damages in rats with diabetic encephalopathy by inhibiting the release of inflammatory cytokines and repairing insulin signaling pathway in hippocampus. Chin J Nat Med 14:813\u2013822. https:\/\/doi.org\/10.1016\/S1875-5364(16)30098-X","journal-title":"Chin J Nat Med"},{"key":"1925_CR44","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1093\/abbs\/gmt069","volume":"45","author":"J Liu","year":"2013","unstructured":"Liu J, Zhang Y, Deng X, Yin F (2013) Geniposide decreases the level of A\u03b21\u201342 in the hippocampus of streptozotocin-induced diabetic rats. Acta Biochim Biophys Sin 45:787\u2013791","journal-title":"Acta Biochim Biophys Sin"},{"key":"1925_CR45","doi-asserted-by":"publisher","first-page":"W159","DOI":"10.1093\/nar\/gkac394","volume":"50","author":"Y Liu","year":"2022","unstructured":"Liu Y, Yang X, Gan J et al (2022) CB-Dock2: improved protein\u2013ligand blind docking by integrating cavity detection, docking and homologous template fitting. Nucleic Acids Res 50:W159\u2013W164","journal-title":"Nucleic Acids Res"},{"key":"1925_CR46","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.lfs.2018.11.053","volume":"217","author":"R Lv","year":"2019","unstructured":"Lv R, Du L, Zhang L, Zhang Z (2019) Polydatin attenuates spinal cord injury in rats by inhibiting oxidative stress and microglia apoptosis via Nrf2\/HO-1 pathway. Life Sci 217:119\u2013127","journal-title":"Life Sci"},{"key":"1925_CR47","doi-asserted-by":"publisher","first-page":"224","DOI":"10.2337\/diab.47.2.224","volume":"47","author":"P Masiello","year":"1998","unstructured":"Masiello P, Broca C, Gross R et al (1998) Experimental NIDDM: development of a new model in adult rats administered streptozotocin and nicotinamide. Diabetes 47:224\u2013229","journal-title":"Diabetes"},{"key":"1925_CR48","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1016\/S0022-3999(02)00307-0","volume":"53","author":"BS McEwen","year":"2002","unstructured":"McEwen BS, Magari\u00f1os AM, Reagan LP (2002) Studies of hormone action in the hippocampal formation: possible relevance to depression and diabetes. J Psychosom Res 53:883\u2013890","journal-title":"J Psychosom Res"},{"key":"1925_CR49","doi-asserted-by":"publisher","first-page":"2785","DOI":"10.1002\/jcc.21256","volume":"30","author":"GM Morris","year":"2009","unstructured":"Morris GM, Huey R, Lindstrom W et al (2009) AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J Comput Chem 30:2785\u20132791. https:\/\/doi.org\/10.1002\/jcc.21256","journal-title":"J Comput Chem"},{"key":"1925_CR50","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.sjbs.2014.05.003","volume":"22","author":"G Mushtaq","year":"2015","unstructured":"Mushtaq G, Khan JA, Kumosani TA, Kamal MA (2015) Alzheimer\u2019s disease and type 2 diabetes via chronic inflammatory mechanisms. Saudi J Biol Sci 22:4\u201313","journal-title":"Saudi J Biol Sci"},{"key":"1925_CR51","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1007\/s11011-024-01438-0","volume":"40","author":"M \u00d6zsan","year":"2024","unstructured":"\u00d6zsan M, Saygili D\u00fczova \u00dc, D\u00f6nmez N (2024) Neuroprotective role of curcumin on the hippocampus against the oxidative stress and inflammation of streptozotocin-induced diabetes in rats. Metab Brain Dis 40:24. https:\/\/doi.org\/10.1007\/s11011-024-01438-0","journal-title":"Metab Brain Dis"},{"key":"1925_CR52","doi-asserted-by":"publisher","first-page":"7303","DOI":"10.3390\/ijms25137303","volume":"25","author":"S Pastene-Burgos","year":"2024","unstructured":"Pastene-Burgos S, Mu\u00f1oz-Nu\u00f1ez E, Quiroz-Carre\u00f1o S et al (2024) Ceanothanes derivatives as peripheric anionic site and catalytic active site inhibitors of acetylcholinesterase: Insights for future drug design. Int J Mol Sci 25:7303","journal-title":"Int J Mol Sci"},{"key":"1925_CR53","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.3390\/life15071006","volume":"15","author":"M Petrovi\u0107","year":"2025","unstructured":"Petrovi\u0107 M, Trenki\u0107 M, Veselinovi\u0107 M et al (2025) Biochemical study of bilberry extract potential in preventing retinal damage in rat model of diabetes induced by streptozotocin\/nicotinamide. Life 15:1006","journal-title":"Life"},{"key":"1925_CR54","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jneuroim.2012.08.008","volume":"254","author":"S Rai","year":"2013","unstructured":"Rai S, Kamat PK, Nath C, Shukla R (2013) A study on neuroinflammation and NMDA receptor function in STZ (ICV) induced memory impaired rats. J Neuroimmunol 254:1\u20139","journal-title":"J Neuroimmunol"},{"key":"1925_CR55","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1016\/j.freeradbiomed.2010.12.006","volume":"50","author":"JL Rains","year":"2011","unstructured":"Rains JL, Jain SK (2011) Oxidative stress, insulin signaling, and diabetes. Free Radic Biol Med 50:567\u2013575","journal-title":"Free Radic Biol Med"},{"key":"1925_CR56","doi-asserted-by":"crossref","unstructured":"Rees TM, Brimijoin S (2003) The role of acetylcholinesterase in the pathogenesis of Alzheimer\u2019s disease. Drugs of today (Barcelona, Spain: 1998) 39:75\u201383","DOI":"10.1358\/dot.2003.39.1.740206"},{"key":"1925_CR57","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1007\/s11064-008-9883-6","volume":"34","author":"C Rivi\u00e8re","year":"2009","unstructured":"Rivi\u00e8re C, Delaunay J-C, Immel F et al (2009) The polyphenol piceid destabilizes preformed amyloid fibrils and oligomers in vitro: hypothesis on possible molecular mechanisms. Neurochem Res 34:1120\u20131128. https:\/\/doi.org\/10.1007\/s11064-008-9883-6","journal-title":"Neurochem Res"},{"key":"1925_CR58","doi-asserted-by":"publisher","first-page":"78","DOI":"10.4103\/2231-4040.133429","volume":"5","author":"S Rondi","year":"2014","unstructured":"Rondi S, Peddolla R, Venisetty RK (2014) Neuro, cardio, and reno protective activities of rosuvastatin in streptozotocin-induced type 2 diabetic rats undergoing treatment with metformin and glimepiride. J Adv Pharm Tech Res 5:78\u201383","journal-title":"J Adv Pharm Tech Res"},{"key":"1925_CR59","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2014\/674987","volume":"2014","author":"R Sandireddy","year":"2014","unstructured":"Sandireddy R, Yerra VG, Areti A et al (2014) Neuroinflammation and oxidative stress in diabetic neuropathy: futuristic strategies based on these targets. Int J Endocrinol 2014:1\u201310. https:\/\/doi.org\/10.1155\/2014\/674987","journal-title":"Int J Endocrinol"},{"key":"1925_CR60","doi-asserted-by":"publisher","first-page":"13098","DOI":"10.3390\/ijms232113098","volume":"23","author":"N Stern","year":"2022","unstructured":"Stern N, Gacs A, T\u00e1trai E et al (2022) Dual inhibitors of AChE and BACE-1 for reducing A\u03b2 in Alzheimer\u2019s disease: from in silico to in vivo. Int J Mol Sci 23:13098","journal-title":"Int J Mol Sci"},{"key":"1925_CR61","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1126\/science.1678899","volume":"253","author":"JL Sussman","year":"1991","unstructured":"Sussman JL, Harel M, Frolow F et al (1991) Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein. Science 253:872\u2013879. https:\/\/doi.org\/10.1126\/science.1678899","journal-title":"Science"},{"key":"1925_CR62","first-page":"605","volume":"43","author":"RE Tanzi","year":"2004","unstructured":"Tanzi RE, Moir RD, Wagner SL (2004) Clearance of Alzheimer\u2019s A\u03b2 peptide: the many roads to perdition. Neuron 43:605\u2013608","journal-title":"Neuron"},{"key":"1925_CR63","doi-asserted-by":"publisher","first-page":"101999","DOI":"10.1016\/j.arr.2023.101999","volume":"90","author":"Y Tian","year":"2023","unstructured":"Tian Y, Jing G, Zhang M (2023) Insulin-degrading enzyme: roles and pathways in ameliorating cognitive impairment associated with Alzheimer\u2019s disease and diabetes. Ageing Res Rev 90:101999","journal-title":"Ageing Res Rev"},{"key":"1925_CR64","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1126\/science.286.5440.735","volume":"286","author":"R Vassar","year":"1999","unstructured":"Vassar R, Bennett BD, Babu-Khan S et al (1999) \u03b2-Secretase cleavage of Alzheimer\u2019s amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286:735\u2013741. https:\/\/doi.org\/10.1126\/science.286.5440.735","journal-title":"Science"},{"key":"1925_CR65","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1021\/acschemneuro.2c00758","volume":"14","author":"J Wang","year":"2023","unstructured":"Wang J, Men Y, Wang Z (2023) Polydatin alleviates chronic stress-induced depressive and anxiety-like behaviors in a mouse model. ACS Chem Neurosci 14:977\u2013987. https:\/\/doi.org\/10.1021\/acschemneuro.2c00758","journal-title":"ACS Chem Neurosci"},{"key":"1925_CR66","doi-asserted-by":"publisher","first-page":"102667","DOI":"10.1016\/j.arr.2025.102667","volume":"104","author":"P Wen","year":"2025","unstructured":"Wen P, Sun Z, Gou F et al (2025) Oxidative stress and mitochondrial impairment: key drivers in neurodegenerative disorders. Ageing Res Rev 104:102667","journal-title":"Ageing Res Rev"},{"key":"1925_CR67","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1017\/S0029665109990206","volume":"68","author":"IS Wood","year":"2009","unstructured":"Wood IS, de Heredia FP, Wang B, Trayhurn P (2009) Cellular hypoxia and adipose tissue dysfunction in obesity: symposium on \u2018Frontiers in Adipose Tissue Biology\u2019. Proc Nutr Soc 68:370\u2013377","journal-title":"Proc Nutr Soc"},{"key":"1925_CR68","doi-asserted-by":"publisher","first-page":"4545","DOI":"10.1039\/C6FO01057A","volume":"7","author":"L-Q Xu","year":"2016","unstructured":"Xu L-Q, Xie Y-L, Gui S-H et al (2016) Polydatin attenuates d-galactose-induced liver and brain damage through its anti-oxidative, anti-inflammatory and anti-apoptotic effects in mice. Food Funct 7:4545\u20134555","journal-title":"Food Funct"},{"key":"1925_CR69","doi-asserted-by":"publisher","first-page":"3877","DOI":"10.4049\/jimmunol.181.6.3877","volume":"181","author":"M Yamamoto","year":"2008","unstructured":"Yamamoto M, Kiyota T, Walsh SM et al (2008) Cytokine-mediated inhibition of fibrillar amyloid-\u03b2 peptide degradation by human mononuclear phagocytes. J Immunol 181:3877\u20133886","journal-title":"J Immunol"},{"key":"1925_CR70","doi-asserted-by":"publisher","first-page":"97","DOI":"10.3389\/fnmol.2017.00097","volume":"10","author":"R Yan","year":"2017","unstructured":"Yan R (2017) Physiological functions of the \u03b2-site amyloid precursor protein cleaving enzyme 1 and 2. Front Mol Neurosci 10:97","journal-title":"Front Mol Neurosci"},{"key":"1925_CR71","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1007\/s12031-017-0922-0","volume":"62","author":"Y Yang","year":"2017","unstructured":"Yang Y, Gao L (2017) Celecoxib alleviates memory deficits by downregulation of COX-2 expression and upregulation of the BDNF-TrkB signaling pathway in a diabetic rat model. J Mol Neurosci 62:188\u2013198. https:\/\/doi.org\/10.1007\/s12031-017-0922-0","journal-title":"J Mol Neurosci"},{"key":"1925_CR72","doi-asserted-by":"publisher","first-page":"675","DOI":"10.4103\/0253-7613.194847","volume":"48","author":"R Yavari","year":"2016","unstructured":"Yavari R, Badalzadeh R, Alipour MR, Tabatabaei SM (2016) Modulation of hippocampal gene expression of microRNA-146a\/microRNA-155-nuclear factor-kappa B inflammatory signaling by troxerutin in healthy and diabetic rats. Indian J Pharmacol 48:675\u2013680","journal-title":"Indian J Pharmacol"},{"key":"1925_CR73","doi-asserted-by":"publisher","first-page":"111027","DOI":"10.1016\/j.biopha.2020.111027","volume":"133","author":"AI Yousef","year":"2021","unstructured":"Yousef AI, Shawki HH, El-Shahawy AA et al (2021) Polydatin mitigates pancreatic \u03b2-cell damage through its antioxidant activity. Biomed Pharmacother 133:111027","journal-title":"Biomed Pharmacother"},{"key":"1925_CR74","doi-asserted-by":"publisher","first-page":"10265","DOI":"10.1021\/jf802095g","volume":"56","author":"K-J Yun","year":"2008","unstructured":"Yun K-J, Koh D-J, Kim S-H et al (2008) Anti-inflammatory effects of sinapic acid through the suppression of inducible nitric oxide synthase, cyclooxygase-2, and proinflammatory cytokines expressions via nuclear factor-\u03baB inactivation. J Agric Food Chem 56:10265\u201310272. https:\/\/doi.org\/10.1021\/jf802095g","journal-title":"J Agric Food Chem"},{"key":"1925_CR75","doi-asserted-by":"publisher","first-page":"117397","DOI":"10.1016\/j.biopha.2024.117397","volume":"179","author":"Q Zhou","year":"2024","unstructured":"Zhou Q, Guo X, Chen T et al (2024) The neuroprotective role of celastrol on hippocampus in diabetic rats by inflammation restraint, insulin signaling adjustment, A\u03b2 reduction and synaptic plasticity alternation. Biomed Pharmacother 179:117397","journal-title":"Biomed Pharmacother"}],"container-title":["Metabolic Brain Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11011-026-01925-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11011-026-01925-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11011-026-01925-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T18:02:15Z","timestamp":1783620135000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11011-026-01925-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,9]]},"references-count":75,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1925"],"URL":"https:\/\/doi.org\/10.1007\/s11011-026-01925-6","relation":{},"ISSN":["1573-7365"],"issn-type":[{"value":"1573-7365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,9]]},"assertion":[{"value":"30 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors approved this version of the manuscript for publication.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"162"}}