Molecular Mechanisms Underlying the Therapeutic Effects of Corydalis yanhusuo on Osteoporosis

Molecular Mechanisms Underlying the Therapeutic Effects of Corydalis yanhusuo on Osteoporosis | 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 Mechanisms Underlying the Therapeutic Effects of Corydalis yanhusuo on Osteoporosis Daning Sun This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9031997/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 13 You are reading this latest preprint version Abstract Objective. Corydalis, a traditional Chinese medicine containing multiple active alkaloids, exhibits potential therapeutic effects on osteoporosis, though its underlying mechanisms remain unclear. This study aims to elucidate the molecular mechanisms of Corydalis in treating osteoporosis through network pharmacology research, providing theoretical support for its clinical application and drug development. Methods : Active components of Corydalis were screened using the TCMSP database (following Lipinski's rules: OB ≥ 30%, DL ≥ 0.18, etc.). Targets were standardized via UniProt and SwissTargetPrediction databases. Osteoporosis-related genes were obtained from DrugBank and GeneCards databases (screened with Score_gda ≥ 0.02 and Relevance ≥ 1.1427, respectively).Identified "drug-disease" intersection genes, constructed protein-protein interaction (PPI) networks using the STRING database and Cytoscape 3.9 to screen core targets; Performed Gene Ontology (GO) and KEGG pathway enrichment analyses using DAVID and Metascape databases; Conducted molecular docking between core targets (HIF1A, JUN, etc.) and active components (binding energy < -5.0 kcal/mol as the validity criterion). Results : 35 active components and 590 drug targets were screened from Corydalis yanhusuo, along with 1,278 osteoporosis-related genes. This yielded 112 intersecting genes, from which 21 core targets were further identified.GO analysis revealed core targets primarily involved in biological processes such as signal transduction, inflammatory response, and cell proliferation regulation. They were enriched in cellular components including plasma membrane and cytoplasm, with protein binding as the predominant molecular function.KEGG analysis indicated significant enrichment of core targets in signaling pathways including PI3K-Akt, MAPK, and AGE-RAGE. Molecular docking validation demonstrated stable hydrogen-bonded interactions between core components of Corydalis and targets such as HIF1A, AKT1, and ESR1 (all binding energies < -5.0 kcal/mol). Conclusion : Corydalis may exert anti-inflammatory effects, regulate glucose metabolism, inhibit osteoclast differentiation, and modulate parathyroid function by regulating signaling pathways such as PI3K-Akt and MAPK through core targets including HIF1A, JUN, and STAT3, thereby improving osteoporosis. This provides research directions for subsequent cellular experiments, animal validation, and clinical treatment. Corydalis yanhusuo Osteoporosis Network pharmacology Signaling pathways Molecular docking Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 23 Apr, 2026 Reviews received at journal 20 Apr, 2026 Reviews received at journal 11 Apr, 2026 Reviews received at journal 10 Apr, 2026 Reviewers agreed at journal 10 Apr, 2026 Reviewers agreed at journal 06 Apr, 2026 Reviews received at journal 03 Apr, 2026 Reviewers agreed at journal 02 Apr, 2026 Reviewers agreed at journal 26 Mar, 2026 Reviewers invited by journal 15 Mar, 2026 Editor assigned by journal 05 Mar, 2026 Submission checks completed at journal 05 Mar, 2026 First submitted to journal 04 Mar, 2026 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. 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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-9031997","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":606634086,"identity":"cc02120a-620a-4c86-867c-4992116818b4","order_by":0,"name":"Daning Sun","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyklEQVRIiWNgGAWjYFCCBOYHHypsEiDsAuK0sBnOOJOWwMAGYhsQp4VBmrPtMEQLAzFa5NtzDxgztp3P45fvTvzwwIBBnl/sAH4tBmfeJTwuOHe7WLKNd7ME0GGGM2cnENAikWNgPKPsduKGY7wbQFoSDG4T0CI/I8dAmoftHEjL5h9EaWG4AdLSdgCkZRtxthiceWMGDOTkxJltudssEgwkCPtFvj3HGBiVdon9zGc33/xRYSPPL03IYWhAgjTlo2AUjIJRMAqwAwBr/kZOpkeAdwAAAABJRU5ErkJggg==","orcid":"","institution":"Fuyong People's Hospital of Bao'an District","correspondingAuthor":true,"prefix":"","firstName":"Daning","middleName":"","lastName":"Sun","suffix":""}],"badges":[],"createdAt":"2026-03-04 15:38:31","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9031997/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9031997/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104808689,"identity":"77595259-3ebc-4866-8de5-8e8d39627882","added_by":"auto","created_at":"2026-03-17 12:39:28","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":936565,"visible":true,"origin":"","legend":"","description":"","filename":"SunCorydalisOsteoporosisManuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9031997/v1_covered_08546c8e-8c06-4f2a-a285-276463dc56f9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Molecular Mechanisms Underlying the Therapeutic Effects of Corydalis yanhusuo on Osteoporosis","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"in-silico-pharmacology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"insp","sideBox":"Learn more about [In Silico Pharmacology](https://link.springer.com/journal/40203)","snPcode":"40203","submissionUrl":"https://submission.nature.com/new-submission/40203/3","title":"In Silico Pharmacology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Corydalis yanhusuo, Osteoporosis, Network pharmacology, Signaling pathways, Molecular docking","lastPublishedDoi":"10.21203/rs.3.rs-9031997/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9031997/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective. \u003c/strong\u003eCorydalis, a traditional Chinese medicine containing multiple active alkaloids, exhibits potential therapeutic effects on osteoporosis, though its underlying mechanisms remain unclear. This study aims to elucidate the molecular mechanisms of Corydalis in treating osteoporosis through network pharmacology research, providing theoretical support for its clinical application and drug development.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: Active components of Corydalis were screened using the TCMSP database (following Lipinski's rules: OB ≥ 30%, DL ≥ 0.18, etc.). Targets were standardized via UniProt and SwissTargetPrediction databases. Osteoporosis-related genes were obtained from DrugBank and GeneCards databases (screened with Score_gda ≥ 0.02 and Relevance ≥ 1.1427, respectively).Identified \"drug-disease\" intersection genes, constructed protein-protein interaction (PPI) networks using the STRING database and Cytoscape 3.9 to screen core targets; Performed Gene Ontology (GO) and KEGG pathway enrichment analyses using DAVID and Metascape databases; Conducted molecular docking between core targets (HIF1A, JUN, etc.) and active components (binding energy \u0026lt; -5.0 kcal/mol as the validity criterion).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: 35 active components and 590 drug targets were screened from Corydalis yanhusuo, along with 1,278 osteoporosis-related genes. This yielded 112 intersecting genes, from which 21 core targets were further identified.GO analysis revealed core targets primarily involved in biological processes such as signal transduction, inflammatory response, and cell proliferation regulation. They were enriched in cellular components including plasma membrane and cytoplasm, with protein binding as the predominant molecular function.KEGG analysis indicated significant enrichment of core targets in signaling pathways including PI3K-Akt, MAPK, and AGE-RAGE. Molecular docking validation demonstrated stable hydrogen-bonded interactions between core components of Corydalis and targets such as HIF1A, AKT1, and ESR1 (all binding energies \u0026lt; -5.0 kcal/mol).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: Corydalis may exert anti-inflammatory effects, regulate glucose metabolism, inhibit osteoclast differentiation, and modulate parathyroid function by regulating signaling pathways such as PI3K-Akt and MAPK through core targets including HIF1A, JUN, and STAT3, thereby improving osteoporosis. This provides research directions for subsequent cellular experiments, animal validation, and clinical treatment.\u003c/p\u003e","manuscriptTitle":"Molecular Mechanisms Underlying the Therapeutic Effects of Corydalis yanhusuo on Osteoporosis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-17 10:16:56","doi":"10.21203/rs.3.rs-9031997/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-23T08:27:12+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-21T03:37:14+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-11T14:11:23+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-10T10:52:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"7778822781973594303544446178007552039","date":"2026-04-10T10:27:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"293176255734902168826015240803715702863","date":"2026-04-06T10:00:23+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-03T12:07:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"169089171859706755951679617208531749162","date":"2026-04-03T01:51:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"309715185052483569493811922742669359948","date":"2026-03-26T08:41:46+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-16T03:49:53+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-05T10:04:04+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-05T09:57:40+00:00","index":"","fulltext":""},{"type":"submitted","content":"In Silico Pharmacology","date":"2026-03-04T15:24:11+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"in-silico-pharmacology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"insp","sideBox":"Learn more about [In Silico Pharmacology](https://link.springer.com/journal/40203)","snPcode":"40203","submissionUrl":"https://submission.nature.com/new-submission/40203/3","title":"In Silico Pharmacology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"08ccb0b0-0f64-4083-828d-78d2382eca6e","owner":[],"postedDate":"March 17th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-04-23T08:38:45+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-17 10:16:56","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9031997","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9031997","identity":"rs-9031997","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}