Network Pharmacology-Guided Identification of Kinase-Mediated Vascular Signalling Targets Underlying the Antihypertensive Potential of Brassica rapa L

Network Pharmacology-Guided Identification of Kinase-Mediated Vascular Signalling Targets Underlying the Antihypertensive Potential of Brassica rapa L | 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 Network Pharmacology-Guided Identification of Kinase-Mediated Vascular Signalling Targets Underlying the Antihypertensive Potential of Brassica rapa L Dipil Dhondsekar, Satish Mandlik, Shrikant Nilewar, Deepa Mandlik This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8953804/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 11 You are reading this latest preprint version Abstract Hypertension is a complex cardiometabolic disorder involving oxidative stress, endothelial dysfunction, inflammation, and neurohormonal imbalance, which increase vascular resistance and remodeling. Consequently, single target treatment frequently has low long-term efficacy. Brassica rapa L. (BRL) turnip, a medicinal and dietary crucifer rich in glucosinolates, flavonoids, phenolic acids, offers significant potential for blood pressure modulation. Through a comprehensive in-silico method that combines network pharmacology, molecular docking, molecular dynamics simulation, and ADMET guided screening, this study examines the multitarget antihypertensive potentiation of BRL. In the list of the 189 phytoconstituents identified through extensive database, 9 drug-like candidates were ultimately selected utilizing SwissADME profiling and Lipinski’s rule of 5. Predicted protein targets identified through SwissTargetPredication and the similarity ensemble approach were cross referenced with hypertension-associated genes from GeneCards and online mendelian inheritance in man, yielding 246 common targets. Protein-protein interaction analysis revealed a core module of 10 hub genes, such as EGFR, PIK3CA, FYN, PTK2, SRC, PTPN11, PIK3R1, CTNNB1, and AKT1 indicating a key role for kinase-driven vascular signaling. Functional enrichment analysis highlighted redox homeostasis, Vaso regulatory balance, and the PI3K-AKT and nitric/eNOS signaling pathways. AutoDock Vina docking identified quercetin (-11.4 kcal/mol), kaempferol and isorhamnetin (-11.2 kcal/mol), gluconasturtiin (-11.2 kcal/mol) as top ligands. Schrodinger molecular dynamics simulations over 100 ns confirmed the stability and energetically favorable nature of the protein-ligand interactions. Overall, BRL demonstrates strong multitarget antihypertensive potential, with prioritized lead molecules for further validation Hypertension Brassica rapa Network pharmacology Molecular docking Molecular dynamics simulation Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 14 May, 2026 Reviews received at journal 13 May, 2026 Reviewers agreed at journal 13 May, 2026 Reviewers agreed at journal 19 Apr, 2026 Reviewers agreed at journal 16 Apr, 2026 Reviews received at journal 14 Apr, 2026 Reviewers agreed at journal 28 Mar, 2026 Reviewers invited by journal 02 Mar, 2026 Editor assigned by journal 25 Feb, 2026 Submission checks completed at journal 25 Feb, 2026 First submitted to journal 24 Feb, 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. 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-8953804","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":599629994,"identity":"23a1a732-7284-47bb-bf13-a88507db7676","order_by":0,"name":"Dipil Dhondsekar","email":"","orcid":"","institution":"Poona College of Pharmacy","correspondingAuthor":false,"prefix":"","firstName":"Dipil","middleName":"","lastName":"Dhondsekar","suffix":""},{"id":599629997,"identity":"af374c01-841d-4028-8ed3-c293aa0f3714","order_by":1,"name":"Satish Mandlik","email":"","orcid":"","institution":"Poona College of Pharmacy","correspondingAuthor":false,"prefix":"","firstName":"Satish","middleName":"","lastName":"Mandlik","suffix":""},{"id":599629998,"identity":"43ac608f-5e84-400e-834c-08338e317e8c","order_by":2,"name":"Shrikant Nilewar","email":"","orcid":"","institution":"Maliba Pharmacy College, Uka Tarsadia University","correspondingAuthor":false,"prefix":"","firstName":"Shrikant","middleName":"","lastName":"Nilewar","suffix":""},{"id":599629999,"identity":"f1c825a9-9d88-41a0-a795-11941ff5f47c","order_by":3,"name":"Deepa Mandlik","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABA0lEQVRIiWNgGAWjYDCCA2BSAsJ5wGADZxOpJYEhjWgtDDAthwlr4TvefOzBDwaLPHn3M4YfEirOJ/bPbj74gKHGJhqXFskzx9INexgkig3P5BhLJJy5nTjjzrFkA4ZjabkNOLQY3Mgxk+BhkEjc2JC7QSKx7XZiA0iEseEwbi3333+T/APS0v9284/Ef+cS5xPUcoOHTRpky3yJ3G0SiQ0HEjcQ0iJ5Js3cWAaoZYPE+28WCceSjTfeSEs2SMDjF77jh589fMNQlzi/Py35xocaO9l5N5IPPvhQY4NTCxCwMTD+A7rwAITnCFaZgFs5RAsIyEMNtceveBSMglEwCkYiAACkxmOf2TXb6QAAAABJRU5ErkJggg==","orcid":"","institution":"Poona College of Pharmacy","correspondingAuthor":true,"prefix":"","firstName":"Deepa","middleName":"","lastName":"Mandlik","suffix":""}],"badges":[],"createdAt":"2026-02-24 07:09:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8953804/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8953804/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104402601,"identity":"6cbea09a-f805-4792-a442-82cb1a12f437","added_by":"auto","created_at":"2026-03-11 12:15:51","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3234084,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8953804/v1_covered_47006761-2efc-4e54-b552-2d17cf336d3d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Network Pharmacology-Guided Identification of Kinase-Mediated Vascular Signalling Targets Underlying the Antihypertensive Potential of Brassica rapa L","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":"Hypertension, Brassica rapa, Network pharmacology, Molecular docking, Molecular dynamics simulation","lastPublishedDoi":"10.21203/rs.3.rs-8953804/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8953804/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eHypertension is a complex cardiometabolic disorder involving oxidative stress, endothelial dysfunction, inflammation, and neurohormonal imbalance, which increase vascular resistance and remodeling. Consequently, single target treatment frequently has low long-term efficacy. \u003cem\u003eBrassica rapa\u003c/em\u003e L. (BRL) turnip, a medicinal and dietary crucifer rich in glucosinolates, flavonoids, phenolic acids, offers significant potential for blood pressure modulation. Through a comprehensive \u003cem\u003ein-silico\u003c/em\u003e method that combines network pharmacology, molecular docking, molecular dynamics simulation, and ADMET guided screening, this study examines the multitarget antihypertensive potentiation of BRL. In the list of the 189 phytoconstituents identified through extensive database, 9 drug-like candidates were ultimately selected utilizing SwissADME profiling and Lipinski\u0026rsquo;s rule of 5. Predicted protein targets identified through SwissTargetPredication and the similarity ensemble approach were cross referenced with hypertension-associated genes from GeneCards and online mendelian inheritance in man, yielding 246 common targets. Protein-protein interaction analysis revealed a core module of 10 hub genes, such as EGFR, PIK3CA, FYN, PTK2, SRC, PTPN11, PIK3R1, CTNNB1, and AKT1 indicating a key role for kinase-driven vascular signaling. Functional enrichment analysis highlighted redox homeostasis, Vaso regulatory balance, and the PI3K-AKT and nitric/eNOS signaling pathways. AutoDock Vina docking identified quercetin (-11.4 kcal/mol), kaempferol and isorhamnetin (-11.2 kcal/mol), gluconasturtiin (-11.2 kcal/mol) as top ligands. Schrodinger molecular dynamics simulations over 100 ns confirmed the stability and energetically favorable nature of the protein-ligand interactions. Overall, BRL demonstrates strong multitarget antihypertensive potential, with prioritized lead molecules for further validation\u003c/p\u003e","manuscriptTitle":"Network Pharmacology-Guided Identification of Kinase-Mediated Vascular Signalling Targets Underlying the Antihypertensive Potential of Brassica rapa L","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-05 18:37:40","doi":"10.21203/rs.3.rs-8953804/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-05-14T23:35:16+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-13T18:04:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"107515196328037355302518230154444629437","date":"2026-05-13T17:55:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"67725001998394754832739017361558508003","date":"2026-04-19T11:20:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"220434402746475346443187950889092910154","date":"2026-04-16T06:12:19+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-14T19:56:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"62261947374022385929009327045155548817","date":"2026-03-28T09:51:17+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-03T00:53:39+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-25T11:23:20+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-25T11:22:58+00:00","index":"","fulltext":""},{"type":"submitted","content":"In Silico Pharmacology","date":"2026-02-24T06:55:27+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":"dad7281b-24b0-483d-ba70-d1998c5de855","owner":[],"postedDate":"March 5th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Revision requested","date":"2026-05-14T23:35:16+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-13T18:04:01+00:00","index":68,"fulltext":""},{"type":"reviewerAgreed","content":"107515196328037355302518230154444629437","date":"2026-05-13T17:55:49+00:00","index":67,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-05-14T23:38:49+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-05 18:37:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8953804","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8953804","identity":"rs-8953804","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}