Synergistic Anti-Hepatocellular Carcinoma Effects of Dendrophthoe Falcata Flavonoids: A Multi-Omics and Computational Investigation of Isorhamnetin and Kaempferol

Synergistic Anti-Hepatocellular Carcinoma Effects of Dendrophthoe Falcata Flavonoids: A Multi-Omics and Computational Investigation of Isorhamnetin and Kaempferol | 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 Synergistic Anti-Hepatocellular Carcinoma Effects of Dendrophthoe Falcata Flavonoids: A Multi-Omics and Computational Investigation of Isorhamnetin and Kaempferol K Valarmathy, Suvechha Mandal, Navana RL, Vyshnavi Sreenivas, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7043500/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 Hepatocellular carcinoma (HCC) remains a leading cause of cancer mortality, often driven by the over expression of oncogenes like TGFBR1. This study investigates the anti-cancer potential of flavonoids—Isorhamnetin and Kaempferol—extracted from Dendrophthoe falcata , a semi-parasitic medicinal plant. Soxhlet extraction followed by LC-MS identified 21 flavonoids. In-vitro assays on HEPG2 cells revealed significant Cytotoxicity (IC₅₀ = 89.76 µg/mL) and 83.11% apoptosis induction. In-silico analyses, including protein–protein interaction networks, gene ontology, and pathway enrichment, confirmed TGFBR1’s role in angiogenesis and apoptosis evasion. Five ADMET-compliant flavonoids were docked with TGFBR1, with Isorhamnetin showing the highest affinity. A dual-flavonoid approach combining Isorhamnetin and Kaempferol exhibited enhanced binding energy (-8.9 kcal/mol) and dynamic stability. Molecular dynamics simulations revealed complex stability with RMSD of 0.36 nm, reduced radius of gyration (2.05 to 1.98 nm), and lower solvent-accessible surface area (160 to 140 nm²). These findings suggest the synergistic flavonoid combination from D. falcata as a promising therapeutic strategy for HCC, warranting further preclinical validation. Hepatocellular carcinoma Dendrophthoe falcate Isorhamnetin Kaempferol Flavonoids Cytotoxicity Apoptosis 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-7043500","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":530297334,"identity":"87b7d00a-792a-4551-82d3-f5c64d52c583","order_by":0,"name":"K Valarmathy","email":"","orcid":"","institution":"The Oxford College of Engineering","correspondingAuthor":false,"prefix":"","firstName":"K","middleName":"","lastName":"Valarmathy","suffix":""},{"id":530297335,"identity":"bf795ad1-0140-4ea3-be2e-5f777a34de84","order_by":1,"name":"Suvechha Mandal","email":"","orcid":"","institution":"The Oxford College of 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Kaempferol\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":"Hepatocellular carcinoma, Dendrophthoe falcate, Isorhamnetin, Kaempferol, Flavonoids, Cytotoxicity, Apoptosis","lastPublishedDoi":"10.21203/rs.3.rs-7043500/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7043500/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eHepatocellular carcinoma (HCC) remains a leading cause of cancer mortality, often driven by the over expression of oncogenes like TGFBR1. This study investigates the anti-cancer potential of flavonoids\u0026mdash;Isorhamnetin and Kaempferol\u0026mdash;extracted from \u003cem\u003eDendrophthoe falcata\u003c/em\u003e, a semi-parasitic medicinal plant. Soxhlet extraction followed by LC-MS identified 21 flavonoids. In-vitro assays on HEPG2 cells revealed significant Cytotoxicity (IC₅₀ = 89.76 \u0026micro;g/mL) and 83.11% apoptosis induction. In-silico analyses, including protein\u0026ndash;protein interaction networks, gene ontology, and pathway enrichment, confirmed TGFBR1\u0026rsquo;s role in angiogenesis and apoptosis evasion. Five ADMET-compliant flavonoids were docked with TGFBR1, with Isorhamnetin showing the highest affinity. A dual-flavonoid approach combining Isorhamnetin and Kaempferol exhibited enhanced binding energy (-8.9 kcal/mol) and dynamic stability. Molecular dynamics simulations revealed complex stability with RMSD of 0.36 nm, reduced radius of gyration (2.05 to 1.98 nm), and lower solvent-accessible surface area (160 to 140 nm\u0026sup2;). These findings suggest the synergistic flavonoid combination from \u003cem\u003eD. falcata\u003c/em\u003e as a promising therapeutic strategy for HCC, warranting further preclinical validation.\u003c/p\u003e","manuscriptTitle":"Synergistic Anti-Hepatocellular Carcinoma Effects of Dendrophthoe Falcata Flavonoids: A Multi-Omics and Computational Investigation of Isorhamnetin and Kaempferol","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-16 14:17:29","doi":"10.21203/rs.3.rs-7043500/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":"c31dc86b-469f-4888-8cb2-241c701e267e","owner":[],"postedDate":"October 16th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-10-27T14:40:15+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-16 14:17:29","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7043500","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7043500","identity":"rs-7043500","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}