Quercetin protects chicken mesenchymal stem cells from DEHP- induced toxicity by modulating the ROS/Wnt/β-catenin pathway

Quercetin protects chicken mesenchymal stem cells from DEHP- induced toxicity by modulating the ROS/Wnt/β-catenin pathway | 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 Quercetin protects chicken mesenchymal stem cells from DEHP- induced toxicity by modulating the ROS/Wnt/β-catenin pathway Huiling Zheng, Xinyu Huo, Chenxi Huang, Wenwen Zhang, Kang Yang, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7530959/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Di-2-ethylhexyl phthalate (DEHP), a ubiquitous plasticizer, induces systemic organ damage primarily via oxidative stress. Quercetin (Que), a flavonoid abundant in vegetables, possesses anti-inflammatory, anti-allergic, and antioxidant properties. Whether Que protects avian gizzard tissue against DEHP insult through modulation of the ROS/Wnt/β-catenin axis remains unclear. Network toxicology indicated that DEHP could trigger chicken gastritis via oxidative stress, apoptosis, and autophagy. In vitro and in vivo experiments corroborated these predictions: DEHP exposure markedly elevated oxidative stress, suppressed Wnt/β-catenin signaling at both protein and mRNA levels, down-regulated autophagy-related genes, and up-regulated pro-apoptotic markers. Concomitant Que treatment reversed these alterations. Importantly, the protective effect of Que was abolished when either the oxidative-stress activator sanguinarine or the pathway inhibitor Wnt-C59 was added. Collectively, Que modulates the Wnt/β-catenin pathway in a ROS-dependent manner, thereby inhibiting DEHP-induced apoptosis and restoring autophagy in chicken gizzard mesenchymal stem cells. These findings provide new insights into the toxicology of DEHP in poultry and wild birds, and support the development of plant-derived formulations to prevent or mitigate phthalate poisoning in livestock. Quercetin DEHP ROS Gizzard mesenchymal stem cells Autophagy Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 13 Jan, 2026 Reviews received at journal 09 Jan, 2026 Reviews received at journal 08 Jan, 2026 Reviewers agreed at journal 22 Dec, 2025 Reviewers agreed at journal 21 Dec, 2025 Reviews received at journal 21 Nov, 2025 Reviewers agreed at journal 11 Nov, 2025 Reviewers invited by journal 26 Oct, 2025 Editor assigned by journal 04 Sep, 2025 Submission checks completed at journal 04 Sep, 2025 First submitted to journal 03 Sep, 2025 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. 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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-7530959","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":536521594,"identity":"5245baa5-42e4-4f1f-adf4-3d73c992ab4a","order_by":0,"name":"Huiling Zheng","email":"","orcid":"","institution":"Northeast Agricultural University","correspondingAuthor":false,"prefix":"","firstName":"Huiling","middleName":"","lastName":"Zheng","suffix":""},{"id":536521595,"identity":"e06b840f-8d8a-4024-b4f1-92775fcdf23f","order_by":1,"name":"Xinyu Huo","email":"","orcid":"","institution":"Northeast Agricultural 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pathway","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"one-health-advances","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [One Health Advances](https://onehealthadv.biomedcentral.com/)","snPcode":"44280","submissionUrl":"https://submission.springernature.com/new-submission/44280/3","title":"One Health Advances","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Quercetin, DEHP, ROS, Gizzard mesenchymal stem cells, Autophagy","lastPublishedDoi":"10.21203/rs.3.rs-7530959/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7530959/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eDi-2-ethylhexyl phthalate (DEHP), a ubiquitous plasticizer, induces systemic organ damage primarily via oxidative stress. Quercetin (Que), a flavonoid abundant in vegetables, possesses anti-inflammatory, anti-allergic, and antioxidant properties. Whether Que protects avian gizzard tissue against DEHP insult through modulation of the ROS/Wnt/β-catenin axis remains unclear. Network toxicology indicated that DEHP could trigger chicken gastritis via oxidative stress, apoptosis, and autophagy. In vitro and in vivo experiments corroborated these predictions: DEHP exposure markedly elevated oxidative stress, suppressed Wnt/β-catenin signaling at both protein and mRNA levels, down-regulated autophagy-related genes, and up-regulated pro-apoptotic markers. Concomitant Que treatment reversed these alterations. Importantly, the protective effect of Que was abolished when either the oxidative-stress activator sanguinarine or the pathway inhibitor Wnt-C59 was added. Collectively, Que modulates the Wnt/β-catenin pathway in a ROS-dependent manner, thereby inhibiting DEHP-induced apoptosis and restoring autophagy in chicken gizzard mesenchymal stem cells. These findings provide new insights into the toxicology of DEHP in poultry and wild birds, and support the development of plant-derived formulations to prevent or mitigate phthalate poisoning in livestock.\u003c/p\u003e","manuscriptTitle":"Quercetin protects chicken mesenchymal stem cells from DEHP- induced toxicity by modulating the ROS/Wnt/β-catenin pathway","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-05 13:28:53","doi":"10.21203/rs.3.rs-7530959/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-13T15:10:43+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-10T01:53:17+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-08T06:12:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"201285905649707880527322299570442995723","date":"2025-12-22T10:01:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"116770034465453907098393355224654165408","date":"2025-12-22T03:24:17+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-21T07:02:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"113145191465487593276950886522295057952","date":"2025-11-11T08:10:01+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-27T02:07:03+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-04T10:39:33+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-04T10:38:38+00:00","index":"","fulltext":""},{"type":"submitted","content":"One Health Advances","date":"2025-09-04T01:28:32+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"one-health-advances","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [One Health Advances](https://onehealthadv.biomedcentral.com/)","snPcode":"44280","submissionUrl":"https://submission.springernature.com/new-submission/44280/3","title":"One Health Advances","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5b1ee670-6ef4-4e08-be34-e8c7ba504c8b","owner":[],"postedDate":"November 5th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-01-22T00:38:15+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-05 13:28:53","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7530959","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7530959","identity":"rs-7530959","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}