Watermelon seeds in modulating oxidative stress and inflammatory pathways in rheumatoid arthritis: In Silico and In Vivo Insights

Watermelon seeds in modulating oxidative stress and inflammatory pathways in rheumatoid arthritis: In Silico and In Vivo Insights | 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 Watermelon seeds in modulating oxidative stress and inflammatory pathways in rheumatoid arthritis: In Silico and In Vivo Insights Syeda Khimar Zahra Kazmi, Adnan Amjad, Zafarullah Muhammad, Muhammad Maaz, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8734501/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 Objective This study targeted watermelon (Citrullus lanatus) seed powder (WSP) to evaluate its nutritional composition, antioxidant activity, and in silico as well as in vivo anti-arthritic potential in male Sprague Dawley rats. Methodology : The nutritional contents of WSP were analyzed, followed by the TPC contents and antioxidant activity via DPPH and ABTS assays. Moreover, FTIR spectroscopy was carried out to identify functional compounds. Later, in silico study via molecular docking was performed to assess quercetin, ferulic acid, and β-sitosterol interaction with superoxide dismutase (PDB: 1P7G) for anti-oxidative prediction, which was further confirmed by conducting in vivo study. Results The results revealed promising levels of crude fat (39.62%) and protein (23.84%), with efficient amount of potassium, calcium, and phosphorous. The aqueous ethanolic extract showed the maximum antioxidant activity, as DPPH = 73.50% and ABTS = 80.31 µM Fe 2+ /100g) due to higher TPC (766.7 mgGAE/100g) and TFC (71.47 mgQE/100g) contents. Moreover, molecular docking showed the higher binding affinity (-8.2 kcal/mol) of quercetin than others. In vivo study showed that the reduced CAT & TAC, and increased MDA levels were improved by the 400 mg/kg/day WSP to 58.73 ± 2.87 U/mL, 1.19 ± 0.01 mmol Trolox equivalents/L, and 6.02 ± 0.28 nmol/mL, respectively. Furthermore, inflammatory markers were also improved in G4 (TNF-α = 9.03 ± 0.70 pg/mL, CRP = 0.86 ± 0.03 mg/L, and IL-6 = 5.91 ± 0.13 pg/mL). Additionally, the histopathology showed the more efficient potential of WSP (400 mg/kg BW) in rats. Conclusion WSP demonstrated dose-responsive antioxidant restoration and reduction of systemic inflammation, supporting its low-cost functional and nutraceutical potential. Rheumatoid arthritis watermelon seeds antioxidant activity inflammatory markers molecular docking Full Text Additional Declarations No competing interests reported. Table 2.1, 3,1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, and 3.9 are available in the Supplementary Files section. Supplementary Files Tables.docx 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-8734501","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":582640188,"identity":"aae60825-0b26-447b-a304-341de4cc2df0","order_by":0,"name":"Syeda Khimar Zahra Kazmi","email":"","orcid":"","institution":"Bahauddin Zakariya University","correspondingAuthor":false,"prefix":"","firstName":"Syeda","middleName":"Khimar Zahra","lastName":"Kazmi","suffix":""},{"id":582640192,"identity":"02aaee9d-58d7-45be-90f0-76298a19407b","order_by":1,"name":"Adnan 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docking","lastPublishedDoi":"10.21203/rs.3.rs-8734501/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8734501/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study targeted watermelon \u003cem\u003e(Citrullus lanatus)\u003c/em\u003e seed powder (WSP) to evaluate its nutritional composition, antioxidant activity, and \u003cem\u003ein silico\u003c/em\u003e as well as \u003cem\u003ein vivo\u003c/em\u003e anti-arthritic potential in male Sprague Dawley rats. \u003cstrong\u003eMethodology\u003c/strong\u003e: The nutritional contents of WSP were analyzed, followed by the TPC contents and antioxidant activity via DPPH and ABTS assays. Moreover, FTIR spectroscopy was carried out to identify functional compounds. Later, \u003cem\u003ein silico\u003c/em\u003e study via molecular docking was performed to assess quercetin, ferulic acid, and β-sitosterol interaction with superoxide dismutase (PDB: 1P7G) for anti-oxidative prediction, which was further confirmed by conducting \u003cem\u003ein vivo\u003c/em\u003e study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe results revealed promising levels of crude fat (39.62%) and protein (23.84%), with efficient amount of potassium, calcium, and phosphorous. The aqueous ethanolic extract showed the maximum antioxidant activity, as DPPH = 73.50% and ABTS = 80.31 µM Fe\u003csup\u003e2+\u003c/sup\u003e/100g) due to higher TPC (766.7 mgGAE/100g) and TFC (71.47 mgQE/100g) contents. Moreover, molecular docking showed the higher binding affinity (-8.2 kcal/mol) of quercetin than others. \u003cem\u003eIn vivo\u003c/em\u003e study showed that the reduced CAT \u0026amp; TAC, and increased MDA levels were improved by the 400 mg/kg/day WSP to 58.73 ± 2.87 U/mL, 1.19 ± 0.01 mmol Trolox equivalents/L, and 6.02 ± 0.28 nmol/mL, respectively. Furthermore, inflammatory markers were also improved in G4 (TNF-α = 9.03 ± 0.70 pg/mL, CRP = 0.86 ± 0.03 mg/L, and IL-6 = 5.91 ± 0.13 pg/mL). Additionally, the histopathology showed the more efficient potential of WSP (400 mg/kg BW) in rats.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWSP demonstrated dose-responsive antioxidant restoration and reduction of systemic inflammation, supporting its low-cost functional and nutraceutical potential.\u003c/p\u003e","manuscriptTitle":"Watermelon seeds in modulating oxidative stress and inflammatory pathways in rheumatoid arthritis: In Silico and In Vivo Insights","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-30 13:57:49","doi":"10.21203/rs.3.rs-8734501/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","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}}],"origin":"","ownerIdentity":"42f5b25f-cb97-432a-9f63-98f6ed63027c","owner":[],"postedDate":"January 30th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-01T12:53:19+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-30 13:57:49","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8734501","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8734501","identity":"rs-8734501","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}