Citral reduces alveolar bone loss and inflammatory mediators in ligature-induced periodontitis: implications for novel therapeutic strategies

Citral reduces alveolar bone loss and inflammatory mediators in ligature-induced periodontitis: implications for novel therapeutic strategies | 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 Citral reduces alveolar bone loss and inflammatory mediators in ligature-induced periodontitis: implications for novel therapeutic strategies Wanderson S. Santos, Isabelly G. Solon, Pedro H. Lopes, Glauce C. Nascimento, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6991461/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 27 Oct, 2025 Read the published version in Inflammation Research → Version 1 posted 9 You are reading this latest preprint version Abstract This study investigated the effects of systemic citral administration on healthy and inflamed gingiva, alveolar bone loss, and inflammatory mediators in a rat model of ligature-induced periodontitis, given the limitations and adverse effects of current periodontal therapies. In this model, a ligature was placed around the first lower right molars of adult male rats for either 7 or 15 days to induce periodontitis. Animals received a daily gavage of citral [a mixture of monoterpenoids found in Cymbopogon citratus (lemongrass) essential oil] or vehicle. Alveolar bone loss was quantified by measuring the distance between the cementoenamel junction (CEJ) and the alveolar bone crest (BC) using image analysis software. Gingival levels of TNF-α, IL-1β, IL-6, and IL-10, as well as plasma TNF-α, were determined by ELISA. Nitric oxide (NO) in gingival tissue was measured via chemiluminescence, and MMP-2 activity was analyzed by gelatin zymography. In situ detection of reactive oxygen species (ROS) was used to assess local oxidative stress in the gingival tissue. The results showed that citral had no significant effect on healthy gingiva. However, in animals with periodontitis, 14-day citral treatment significantly reduced alveolar bone loss, decreased pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), increased IL-10, lowered plasma TNF-α, and inhibited both NO production and MMP-2 activity. Additionally, citral attenuated the marked increase in ROS levels observed in the gingival tissue from periodontitis-induced animals. These findings suggest that citral exerts potent anti-inflammatory and antioxidant effects and may represent a promising therapeutic strategy for managing periodontal inflammation and associated bone loss. Cytokine Gingiva Inflammation Matrix Metalloproteinases Nitric Oxide Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 27 Oct, 2025 Read the published version in Inflammation Research → Version 1 posted Editorial decision: Revision requested 24 Aug, 2025 Reviews received at journal 23 Aug, 2025 Reviews received at journal 07 Aug, 2025 Reviewers agreed at journal 04 Aug, 2025 Reviewers agreed at journal 26 Jul, 2025 Reviewers invited by journal 14 Jul, 2025 Editor assigned by journal 01 Jul, 2025 Submission checks completed at journal 01 Jul, 2025 First submitted to journal 27 Jun, 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. 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-6991461","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":485210029,"identity":"771cb9a0-0933-4ff2-a5c4-fa8d24d944a7","order_by":0,"name":"Wanderson S. 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In this model, a ligature was placed around the first lower right molars of adult male rats for either 7 or 15 days to induce periodontitis. Animals received a daily gavage of citral [a mixture of monoterpenoids found in \u003cem\u003eCymbopogon citratus\u003c/em\u003e (lemongrass) essential oil] or vehicle. Alveolar bone loss was quantified by measuring the distance between the cementoenamel junction (CEJ) and the alveolar bone crest (BC) using image analysis software. Gingival levels of TNF-α, IL-1β, IL-6, and IL-10, as well as plasma TNF-α, were determined by ELISA. Nitric oxide (NO) in gingival tissue was measured via chemiluminescence, and MMP-2 activity was analyzed by gelatin zymography. In situ detection of reactive oxygen species (ROS) was used to assess local oxidative stress in the gingival tissue. The results showed that citral had no significant effect on healthy gingiva. 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These findings suggest that citral exerts potent anti-inflammatory and antioxidant effects and may represent a promising therapeutic strategy for managing periodontal inflammation and associated bone loss.\u003c/p\u003e","manuscriptTitle":"Citral reduces alveolar bone loss and inflammatory mediators in ligature-induced periodontitis: implications for novel therapeutic strategies","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-16 22:16:08","doi":"10.21203/rs.3.rs-6991461/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-08-24T17:29:54+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-23T15:12:11+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-07T15:43:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"329842055443982435052581633249919764594","date":"2025-08-04T17:37:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"58206703620733761628594283942382399930","date":"2025-07-26T22:06:58+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-14T13:46:12+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-01T12:44:59+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-01T12:44:31+00:00","index":"","fulltext":""},{"type":"submitted","content":"Inflammation Research","date":"2025-06-27T12:01:28+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"inflammation-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"inre","sideBox":"Learn more about [Inflammation Research](http://link.springer.com/journal/11)","snPcode":"11","submissionUrl":"https://submission.nature.com/new-submission/11/3","title":"Inflammation Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"1537a842-facc-4af7-b354-13bab9494c61","owner":[],"postedDate":"July 16th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-11-03T15:59:04+00:00","versionOfRecord":{"articleIdentity":"rs-6991461","link":"https://doi.org/10.1007/s00011-025-02104-6","journal":{"identity":"inflammation-research","isVorOnly":false,"title":"Inflammation Research"},"publishedOn":"2025-10-27 15:56:51","publishedOnDateReadable":"October 27th, 2025"},"versionCreatedAt":"2025-07-16 22:16:08","video":"","vorDoi":"10.1007/s00011-025-02104-6","vorDoiUrl":"https://doi.org/10.1007/s00011-025-02104-6","workflowStages":[]},"version":"v1","identity":"rs-6991461","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6991461","identity":"rs-6991461","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}