Polyphenols in the Pipeline: Network-Based Docking, Molecular Dynamics and ADMET Studies of Flavonoids against Alzheimer’s disease

Polyphenols in the Pipeline: Network-Based Docking, Molecular Dynamics and ADMET Studies of Flavonoids against Alzheimer’s disease | 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 Polyphenols in the Pipeline: Network-Based Docking, Molecular Dynamics and ADMET Studies of Flavonoids against Alzheimer’s disease Gandhimathi R, Raziya Begum This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9498657/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose: Alzheimer disease (AD) is progressive neurodegenerative disorder that is manifested by cognitive impairment, neuronal degeneration, and cholinergic impairment. The multifactorial nature of its pathology leads to the purpose of this study that will examine multi-target therapeutic approaches with the help of flavonoids polyphenolic compounds that have antioxidant, anti-inflammatory, and neuroprotective effects to examine their presence in the management of AD. Methods: A combination of in silico and in vitro methods was used. Network pharmacology analysis was done to determine shared targets between the chosen flavonoids and AD-related genes which found 233 shared targets and major pathways including PI3K-Akt, MAPK and NF-kB which are commonly involved in neurodegeneration and inflammation. To evaluate the binding affinity of hesperidin, rutin, epigallocatechin gallate (EGCG), and naringin to AD-associated proteins such as AKT1, ESR1, and BCL2, which are very important in the regulation of cell survival and apoptosis, molecular docking experiments were conducted. More so, the stability of the ligand-protein complexes was also confirmed by the molecular dynamics simulations based on the RMSD, RMSF and binding free energies which indicated the presence of stable interactions in agreement with the past computational pharmacology frameworks. The inhibitory effect of hesperidin and EGCG on acetylcholinesterase (AChE) were studied in vitro and showed a concentration-dependent inhibitory effect. It is notable that EGCG was more inhibited at moderate concentrations, whilst both compounds were as active as donepezil at higher concentrations. Results: Results confirmed the computational predictions and indicated the potential of flavonoids as efficient AChE inhibitors. Conclusion: The study highlights the possibility of flavonoids as effective multi-target therapeutic agents in the treatment of Alzheimer disease. Flavonoids Alzheimer In silico studies Molecular dynamic study Network pharmacology Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version 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-9498657","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":628617368,"identity":"6e043d37-47b8-4ec7-8660-971419456216","order_by":0,"name":"Gandhimathi R","email":"data:image/png;base64,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","orcid":"","institution":"Vels Institute of Science and Technology and Advanced Studies (VISTAS) Pallavaram","correspondingAuthor":true,"prefix":"","firstName":"Gandhimathi","middleName":"","lastName":"R","suffix":""},{"id":628617372,"identity":"3f5adba7-92a9-4ca2-86e5-0d7b398b698c","order_by":1,"name":"Raziya Begum","email":"","orcid":"","institution":"Vels Institute of Science and Technology and Advanced Studies (VISTAS) Pallavaram","correspondingAuthor":false,"prefix":"","firstName":"Raziya","middleName":"","lastName":"Begum","suffix":""}],"badges":[],"createdAt":"2026-04-22 16:08:34","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9498657/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9498657/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107955100,"identity":"50af9ebf-760f-4c04-b716-ae66210daa3f","added_by":"auto","created_at":"2026-04-28 02:40:35","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1119399,"visible":true,"origin":"","legend":"","description":"","filename":"RAZIAMANUSCRIPT.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9498657/v1_covered_b045f244-f1df-4830-aee9-0515ab7c1689.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Polyphenols in the Pipeline: Network-Based Docking, Molecular Dynamics and ADMET Studies of Flavonoids against Alzheimer’s disease","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"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":"[email protected]","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":"Flavonoids, Alzheimer, In silico studies, Molecular dynamic study, Network pharmacology","lastPublishedDoi":"10.21203/rs.3.rs-9498657/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9498657/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePurpose: Alzheimer disease (AD) is progressive neurodegenerative disorder that is manifested by cognitive impairment, neuronal degeneration, and cholinergic impairment. 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