{"paper_id":"425621be-a387-4fc2-a4e4-daa767591c24","body_text":"Protective Effects of Curcumin and Resveratrol on Neurodegeneration and Cognitive Dysfunction in a Streptozotocin-induced Alzheimer Rat Model | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Protective Effects of Curcumin and Resveratrol on Neurodegeneration and Cognitive Dysfunction in a Streptozotocin-induced Alzheimer Rat Model Derya Öztürk SÖYLEMEZ, Erdoğan UNUR, Dilek SAĞIR This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6363905/v2 This work is licensed under a CC BY 4.0 License Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Abstract Background: Alzheimer's disease (AD) is a degenerative neurological disorder characterized by progressive impairment of memory, cognition, and behavior. Since current treatment approaches have been unable to significantly slow the progression of the disease, there is an increasing need for new neuroprotective strategies. This study aims to investigate the protective effects of curcumin and resveratrol on neurotoxicity and the resulting cognitive impairments. Methods: A total of 60 male Wistar albino rats were included in the study. On day 1, an experimental Alzheimer’s model was induced by a single intracerebroventricular injection of streptozotocin (STZ) at a dose of 3 mg/kg. Following model induction, the animals were randomly assigned into six groups: Alzheimer’s disease (ALZ) group, ALZ+curcumin (ALZ+CUR) group, ALZ+resveratrol (ALZ+RES) group, ALZ+curcumin+resveratrol (ALZ+CUR+RES) group, SHAM group, and control group. Morris water maze test, open field test and passive avoidance test were used for behavioral tests; GFAP and caspase-3 tests for immunohistochemical analysis; TAS/TOS values for biochemical analysis and Cavalieri method for stereological examination. Results: Behavioral tests demonstrated that curcumin and resveratrol significantly improved neurobehavioral outcomes. Histological analyses revealed that curcumin and resveratrol reduced the density of cells stained with Caspase 3 (+) and glial fibrillary acidic protein (GFAP) (+), thereby alleviating neuronal cell death and astrocyte activation. Stereological analyses demonstrated that curcumin and resveratrol improved the STZ-induced hippocampal volume reduction. Serum levels of Total antioxidative status (TAS) and Total oxidative status (TOS) measured in serum samples indicated that oxidative stress induced by STZ was reduced by curcumin and resveratrol. While these two compounds exhibited neuroprotective effects when administered alone, no such effect was observed when administered together, suggesting that combination therapy did not produce the expected synergistic effect. Conclusion: This study demonstrated that curcumin and resveratrol, when administered alone, reduce oxidative stress and neuroinflammation caused by STZ, prevent neuronal apoptosis, and exhibit significant neuroprotective effects in ALZ, thereby improving learning and memory functions. These findings suggest that curcumin and resveratrol may serve as effective therapeutic agents in the treatment of Alzheimer's disease. Alzheimer's Disease Curcumin Neurodegeneration Cognitive Dysfunction Resveratrol Streptozotocin Full Text Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-6363905\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":471807142,\"identity\":\"4ac760c1-9650-4a7e-9ae8-a06641c32cb1\",\"order_by\":0,\"name\":\"Derya Öztürk SÖYLEMEZ\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Sinop University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Derya\",\"middleName\":\"Öztürk\",\"lastName\":\"SÖYLEMEZ\",\"suffix\":\"\"},{\"id\":471807143,\"identity\":\"0fa05ecd-e095-4d00-994b-965bf7c415a8\",\"order_by\":1,\"name\":\"Erdoğan UNUR\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Erciyes University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Erdoğan\",\"middleName\":\"\",\"lastName\":\"UNUR\",\"suffix\":\"\"},{\"id\":471807144,\"identity\":\"4c0b4c05-020a-46e3-bb30-4195fe4760bf\",\"order_by\":2,\"name\":\"Dilek SAĞIR\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1UlEQVRIiWNgGAWjYDCCw8wNjA0MNgxsEC4zMVoYQVrSkLSwEdJyAKzlMIxLhBa+44yND2f8OW/PJ9187AFDhXVig3zvA7xaJA8zNhtubLud2CZzLN2A4Ux6YgMbuwFeLQaHGdskHzbcTmCTyDGTYGw7DNRCwGVALe0/H/w5Zw/R8o84LW2MG9gOMLaBtTQQoQXkF8mZbcmJbRJp6QYJx9KN29jS8GvhO3/44MeeP3b28jOSjz34UGMt2898DL8WZMDGkMBAREyiahkFo2AUjIJRgA0AAIoMQ2CEDcpxAAAAAElFTkSuQmCC\",\"orcid\":\"\",\"institution\":\"Sinop University\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Dilek\",\"middleName\":\"\",\"lastName\":\"SAĞIR\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2025-04-02 19:38:13\",\"currentVersionCode\":2,\"declarations\":{\"humanSubjects\":false,\"vertebrateSubjects\":false,\"conflictsOfInterestStatement\":false,\"humanSubjectEthicalGuidelines\":false,\"humanSubjectConsent\":false,\"humanSubjectClinicalTrial\":false,\"humanSubjectCaseReport\":false,\"vertebrateSubjectEthicalGuidelines\":false},\"doi\":\"10.21203/rs.3.rs-6363905/v2\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-6363905/v2\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":90922178,\"identity\":\"dbeb96cd-fea0-4504-8e76-12c976770cb3\",\"added_by\":\"auto\",\"created_at\":\"2025-09-09 15:03:30\",\"extension\":\"pdf\",\"order_by\":1,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":923517,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscriptbmcneuroscience.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-6363905/v2_covered_5a1f8154-0bc2-41b2-836f-aefa502daa93.pdf\"}],\"financialInterests\":\"The authors declare no competing interests.\",\"formattedTitle\":\"Protective Effects of Curcumin and Resveratrol on Neurodegeneration and Cognitive Dysfunction in a Streptozotocin-induced Alzheimer Rat Model\",\"fulltext\":[],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":false,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":true,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":true,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Alzheimer's Disease, Curcumin, Neurodegeneration, Cognitive Dysfunction, Resveratrol, Streptozotocin\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-6363905/v2\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-6363905/v2\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eBackground: \\u003c/strong\\u003eAlzheimer's disease (AD) is a degenerative neurological disorder characterized by progressive impairment of memory, cognition, and behavior. Since current treatment approaches have been unable to significantly slow the progression of the disease, there is an increasing need for new neuroprotective strategies. This study aims to investigate the protective effects of curcumin and resveratrol on neurotoxicity and the resulting cognitive impairments.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMethods: \\u003c/strong\\u003eA total of 60 male Wistar albino rats were included in the study. On day 1, an experimental Alzheimer’s model was induced by a single intracerebroventricular injection of streptozotocin (STZ) at a dose of 3 mg/kg. Following model induction, the animals were randomly assigned into six groups: Alzheimer’s disease (ALZ) group, ALZ+curcumin (ALZ+CUR) group, ALZ+resveratrol (ALZ+RES) group, ALZ+curcumin+resveratrol (ALZ+CUR+RES) group, SHAM group, and control group. Morris water maze test, open field test and passive avoidance test were used for behavioral tests; GFAP and caspase-3 tests for immunohistochemical analysis; TAS/TOS values for biochemical analysis and Cavalieri method for stereological examination.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eResults: \\u003c/strong\\u003eBehavioral tests demonstrated that curcumin and resveratrol significantly improved neurobehavioral outcomes. Histological analyses revealed that curcumin and resveratrol reduced the density of cells stained with Caspase 3 (+) and glial fibrillary acidic protein (GFAP) (+), thereby alleviating neuronal cell death and astrocyte activation. Stereological analyses demonstrated that curcumin and resveratrol improved the STZ-induced hippocampal volume reduction. Serum levels of Total antioxidative status (TAS) and Total oxidative status (TOS) measured in serum samples indicated that oxidative stress induced by STZ was reduced by curcumin and resveratrol. While these two compounds exhibited neuroprotective effects when administered alone, no such effect was observed when administered together, suggesting that combination therapy did not produce the expected synergistic effect.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConclusion: \\u003c/strong\\u003eThis study demonstrated that curcumin and resveratrol, when administered alone, reduce oxidative stress and neuroinflammation caused by STZ, prevent neuronal apoptosis, and exhibit significant neuroprotective effects in ALZ, thereby improving learning and memory functions. These findings suggest that curcumin and resveratrol may serve as effective therapeutic agents in the treatment of Alzheimer's disease.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Protective Effects of Curcumin and Resveratrol on Neurodegeneration and Cognitive Dysfunction in a Streptozotocin-induced Alzheimer Rat Model\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":2,\"date\":\"2025-09-09 14:47:22\",\"doi\":\"10.21203/rs.3.rs-6363905/v2\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}},{\"code\":1,\"date\":\"2025-06-16 08:20:12\",\"doi\":\"10.21203/rs.3.rs-6363905/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"9e5bddb7-b030-4c5d-8930-6efc13dfc433\",\"owner\":[],\"postedDate\":\"September 9th, 2025\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2025-09-19T09:53:23+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2025-09-09 14:47:22\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v2\",\"identity\":\"rs-6363905\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-6363905\",\"identity\":\"rs-6363905\",\"version\":[\"v2\"]},\"buildId\":\"8U1c8b4HqxoKbykW_rLl7\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}