Systems Pharmacology and Molecular Dynamics Elucidate Hedyotis Diffusae Herba - Scuttellaria Barbatae Herba Drug Pair Synergistically Suppresses Prostate Cancer via Apoptosis Signaling Axis

Systems Pharmacology and Molecular Dynamics Elucidate Hedyotis Diffusae Herba - Scuttellaria Barbatae Herba Drug Pair Synergistically Suppresses Prostate Cancer via Apoptosis Signaling Axis | 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 Article Systems Pharmacology and Molecular Dynamics Elucidate Hedyotis Diffusae Herba - Scuttellaria Barbatae Herba Drug Pair Synergistically Suppresses Prostate Cancer via Apoptosis Signaling Axis Junfeng Qiu, Litong Wu, Zhiming Hong, Yahong Shi, Yi Wei, Quan Wang, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7435786/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 17 Dec, 2025 Read the published version in Scientific Reports → Version 1 posted 11 You are reading this latest preprint version Abstract Prostate cancer (PCa), a globally prevalent male malignancy, necessitates breakthroughs in treating its hormone-refractory stage. The Traditional Chinese Medicine drug pair Hedyotis Diffusae Herba – Scutellaria Barbatae Herba (HDH–SBH) shows significant antitumor value, but its multi-component synergistic mechanisms remain unclear. This study elucidated HDH-SBH’s molecular mechanisms in suppressing PCa via apoptosis pathways. Network pharmacology predicted active components (quercetin, ursolic acid, apigenin) and core targets (AKT1, BCL2, NFKB) enriched in apoptosis ( P < 0.05). Molecular docking revealed strong binding (e.g., ursolic acid-AKT1: -7.76 kcal/mol), confirmed by stable 100 ns molecular dynamics simulations (RMSD < 5.0 Å). In vitro, HDH-SBH significantly inhibited PC-3 cell proliferation (48 h IC 50 = 1.094 mg/mL), reduced migration (36 h rate decreased by 64.2%), and induced apoptosis (rate 13.57% vs control 4.79%). It downregulated BCL2 and p-65 protein expression ( P < 0.05) while enhancing AKT1 phosphorylation. Thus, HDH-SBH synergistically targets the AKT1/BCL2/NFKB axis to regulate apoptosis and suppress PCa progression, providing a theoretical and experimental foundation for modernizing TCM in antitumor research. Biological sciences/Cancer Biological sciences/Drug discovery Health sciences/Oncology Prostate cancer Hedyotis Diffusae Herba Scuttellaria Barbatae Herba PC-3 Apoptosis Network pharmacology Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 17 Dec, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 01 Oct, 2025 Reviews received at journal 26 Sep, 2025 Reviews received at journal 24 Sep, 2025 Reviewers agreed at journal 19 Sep, 2025 Reviewers agreed at journal 18 Sep, 2025 Reviewers agreed at journal 17 Sep, 2025 Reviewers invited by journal 16 Sep, 2025 Editor assigned by journal 16 Sep, 2025 Editor invited by journal 02 Sep, 2025 Submission checks completed at journal 26 Aug, 2025 First submitted to journal 26 Aug, 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-7435786","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":519983332,"identity":"6d7aa1bc-24ec-4f70-b826-1fc3bff4dc1d","order_by":0,"name":"Junfeng Qiu","email":"","orcid":"","institution":"Shenzhen Traditional Chinese Medicine Hospital","correspondingAuthor":false,"prefix":"","firstName":"Junfeng","middleName":"","lastName":"Qiu","suffix":""},{"id":519983333,"identity":"545ebc5b-5b3a-44a4-9aa5-96fb9165e356","order_by":1,"name":"Litong Wu","email":"","orcid":"","institution":"Shenzhen Traditional Chinese Medicine 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Axis","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Prostate cancer, Hedyotis Diffusae Herba, Scuttellaria Barbatae Herba, PC-3, Apoptosis, Network pharmacology","lastPublishedDoi":"10.21203/rs.3.rs-7435786/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7435786/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eProstate cancer (PCa), a globally prevalent male malignancy, necessitates breakthroughs in treating its hormone-refractory stage. The Traditional Chinese Medicine drug pair Hedyotis Diffusae Herba \u0026ndash; Scutellaria Barbatae Herba (HDH\u0026ndash;SBH) shows significant antitumor value, but its multi-component synergistic mechanisms remain unclear. This study elucidated HDH-SBH\u0026rsquo;s molecular mechanisms in suppressing PCa via apoptosis pathways. Network pharmacology predicted active components (quercetin, ursolic acid, apigenin) and core targets (AKT1, BCL2, NFKB) enriched in apoptosis (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Molecular docking revealed strong binding (e.g., ursolic acid-AKT1: -7.76 kcal/mol), confirmed by stable 100 ns molecular dynamics simulations (RMSD\u0026thinsp;\u0026lt;\u0026thinsp;5.0 \u0026Aring;). In vitro, HDH-SBH significantly inhibited PC-3 cell proliferation (48 h IC\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;1.094 mg/mL), reduced migration (36 h rate decreased by 64.2%), and induced apoptosis (rate 13.57% vs control 4.79%). It downregulated BCL2 and p-65 protein expression (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) while enhancing AKT1 phosphorylation. Thus, HDH-SBH synergistically targets the AKT1/BCL2/NFKB axis to regulate apoptosis and suppress PCa progression, providing a theoretical and experimental foundation for modernizing TCM in antitumor research.\u003c/p\u003e","manuscriptTitle":"Systems Pharmacology and Molecular Dynamics Elucidate Hedyotis Diffusae Herba - Scuttellaria Barbatae Herba Drug Pair Synergistically Suppresses Prostate Cancer via Apoptosis Signaling Axis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-25 17:29:19","doi":"10.21203/rs.3.rs-7435786/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-01T04:03:02+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-26T09:21:09+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-24T12:35:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"232625460102136354494712805539856500552","date":"2025-09-19T04:42:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"21155866112426178720606631829396551163","date":"2025-09-18T04:38:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"87170236674023451768831973331210812591","date":"2025-09-18T03:41:33+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-16T21:22:45+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-16T21:07:56+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-09-02T12:24:34+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-26T08:58:59+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-08-26T08:55:37+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a12cf1ae-3889-4246-b357-e353bfb9679e","owner":[],"postedDate":"September 25th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":55268332,"name":"Biological sciences/Cancer"},{"id":55268333,"name":"Biological sciences/Drug discovery"},{"id":55268334,"name":"Health sciences/Oncology"}],"tags":[],"updatedAt":"2025-12-22T16:01:13+00:00","versionOfRecord":{"articleIdentity":"rs-7435786","link":"https://doi.org/10.1038/s41598-025-32757-6","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-12-17 15:57:11","publishedOnDateReadable":"December 17th, 2025"},"versionCreatedAt":"2025-09-25 17:29:19","video":"","vorDoi":"10.1038/s41598-025-32757-6","vorDoiUrl":"https://doi.org/10.1038/s41598-025-32757-6","workflowStages":[]},"version":"v1","identity":"rs-7435786","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7435786","identity":"rs-7435786","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}