Molecular Modelling and Biochemical Investigation of Aspilia Africana on Oxido-inflammatory and Apoptotic Responses in Phenanthrene-induced Cadiorenal Toxicity in Rats

Molecular Modelling and Biochemical Investigation of Aspilia Africana on Oxido-inflammatory and Apoptotic Responses in Phenanthrene-induced Cadiorenal Toxicity in Rats | 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 Molecular Modelling and Biochemical Investigation of Aspilia Africana on Oxido-inflammatory and Apoptotic Responses in Phenanthrene-induced Cadiorenal Toxicity in Rats Ayomide Israel Ajayi, Heritage Esther Omoju, Ayomide Oyatoro, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8272030/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 The widespread environmental exposure to phenanthrene (PHE), a polycyclic aromatic hydrocarbon (PAH), presents a significant toxicological concern, particularly for the heart and kidney, through mechanisms involving oxidative stress, inflammation, and apoptosis. This study investigated the protective effects of Aspilia africana (AA) aqueous extract and chrysin against PHE-induced cardiorenal toxicity in rats, and further explored their molecular interactions and pharmacokinetic properties through in silico modelling. Cardiorenal toxicity was induced by oral administration of PHE for 26 days, followed by treatment with AA (500 or 750 mg/kg) or chrysin (25 mg/kg) for 18 days. Serum and tissue biomarkers of renal and cardiac function, oxidative stress, inflammation, and apoptosis were evaluated. Molecular docking and ADMET analyses were performed using CB-Dock, Mcule, and SwissADME servers. PHE administration significantly elevated serum urea, creatinine, cystatin C, cardiac CK-MB, and troponins I and T, while reducing eGFR and antioxidant enzyme activities (SOD, CAT, GPx). Inflammatory cytokines (IL-1β, TNF-α) and pro-apoptotic markers (caspase-3, Bax, p53) were upregulated, whereas IL-10 and Bcl-2 were suppressed. Treatment with AA or chrysin markedly ameliorated these alterations. Docking revealed strong binding affinities (− 10.4 to − 7.5 kcal/mol) of seven AA bioactives—α-pinene, betulin, apigenin, caryophyllene, germacrene D, phytol, and quercetin—toward SGLT1 and GLP-1 receptors. ADMET profiling indicated favourable drug-likeness, high gastrointestinal absorption, and low toxicity. These findings suggest that Aspilia africana confers potent cardiorenal protection against phenanthrene-induced toxicity by attenuating oxidative stress, inflammation, and apoptosis, supported by computational validation of its bioactive constituents. Aspilia africana phenanthrene oxidative stress apoptosis inflammation molecular docking ADMET cardiorenal toxicity 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-8272030","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":557861992,"identity":"e9772317-b3df-44c4-89b4-bc2a56a57557","order_by":0,"name":"Ayomide Israel Ajayi","email":"","orcid":"","institution":"Federal University Oye Ekiti","correspondingAuthor":false,"prefix":"","firstName":"Ayomide","middleName":"Israel","lastName":"Ajayi","suffix":""},{"id":557861993,"identity":"0aeff719-b2a0-40cb-a22a-5cdb32c4c6f7","order_by":1,"name":"Heritage Esther Omoju","email":"","orcid":"","institution":"Federal University Oye 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Rats\u003c/p\u003e","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":"[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":"Aspilia africana, phenanthrene, oxidative stress, apoptosis, inflammation, molecular docking, 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This study investigated the protective effects of \u003cem\u003eAspilia africana\u003c/em\u003e (AA) aqueous extract and chrysin against PHE-induced cardiorenal toxicity in rats, and further explored their molecular interactions and pharmacokinetic properties through in silico modelling. Cardiorenal toxicity was induced by oral administration of PHE for 26 days, followed by treatment with AA (500 or 750 mg/kg) or chrysin (25 mg/kg) for 18 days. Serum and tissue biomarkers of renal and cardiac function, oxidative stress, inflammation, and apoptosis were evaluated. Molecular docking and ADMET analyses were performed using CB-Dock, Mcule, and SwissADME servers. PHE administration significantly elevated serum urea, creatinine, cystatin C, cardiac CK-MB, and troponins I and T, while reducing eGFR and antioxidant enzyme activities (SOD, CAT, GPx). Inflammatory cytokines (IL-1β, TNF-α) and pro-apoptotic markers (caspase-3, Bax, p53) were upregulated, whereas IL-10 and Bcl-2 were suppressed. Treatment with AA or chrysin markedly ameliorated these alterations. Docking revealed strong binding affinities (\u0026minus;\u0026thinsp;10.4 to \u0026minus;\u0026thinsp;7.5 kcal/mol) of seven AA bioactives\u0026mdash;α-pinene, betulin, apigenin, caryophyllene, germacrene D, phytol, and quercetin\u0026mdash;toward SGLT1 and GLP-1 receptors. ADMET profiling indicated favourable drug-likeness, high gastrointestinal absorption, and low toxicity. These findings suggest that \u003cem\u003eAspilia africana\u003c/em\u003e confers potent cardiorenal protection against phenanthrene-induced toxicity by attenuating oxidative stress, inflammation, and apoptosis, supported by computational validation of its bioactive constituents.\u003c/p\u003e","manuscriptTitle":"Molecular Modelling and Biochemical Investigation of Aspilia Africana on Oxido-inflammatory and Apoptotic Responses in Phenanthrene-induced Cadiorenal Toxicity in Rats","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-11 09:45:16","doi":"10.21203/rs.3.rs-8272030/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":"5e643a99-c710-48e9-ab96-f035aee0a1bf","owner":[],"postedDate":"December 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-25T15:10:59+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-11 09:45:16","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8272030","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8272030","identity":"rs-8272030","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}