Mechanistic insights and therapeutic potential of hispidulin in hepatocellular carcinoma: a bioinformatics and experimental study

Mechanistic insights and therapeutic potential of hispidulin in hepatocellular carcinoma: a bioinformatics and experimental study | 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 Mechanistic insights and therapeutic potential of hispidulin in hepatocellular carcinoma: a bioinformatics and experimental study Xulei Zhang, Yuan Yang, Zhiyuan Xu, Miaoyang Chen, Anyin Yang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7961105/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 Background: As a natural compound present in a variety of plants, hispidulin has an inhibitory effect on tumors. Methods: In this study, we combined network pharmacology, bioinformatics methods and experimental verification to explore the potential targets of hispidulin in inhibiting hepatocellular carcinoma. Results: The network pharmacology analysis showed that the pharmacokinetic properties of hispidulin conformed to the Lipinski's five rules, and it had no hepatotoxicity, carcinogenicity, cytotoxicity, immunotoxicity, mutagenicity, and had the potential to be developed as a drug. The results of network pharmacology and bioinformatics analysis showed that hispidulin may interfere with the occurrence and progression of hepatocellular carcinoma by affecting CDK1, SRC, CCNB1, AURKB and PI3K-AKT signaling pathways. In vitro, hispidulin can inhibit the growth of hepatocellular carcinoma, induce apoptosis and inhibit migration of hepatocellular carcinoma cells. Down-regulate the expression of CDK1, CCNB1, SRC, AURKB protein and weaken the PI3K-AKT pathway signal. It has no obvious toxicity to normal liver cells. Conclusions: Hispidin can inhibit the occurrence and progression of hepatocellular carcinoma through multiple targets, showing good anti-tumor efficacy in vitro, and has the potential to develop new therapeutic drugs for hepatocellular carcinoma. hispidulin hepatocellular carcinoma network pharmacology bioinformatics analysis experimental verification 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. 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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-7961105","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":535722505,"identity":"01bb825b-98d6-4a05-8844-04f464d3482b","order_by":0,"name":"Xulei 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verification","lastPublishedDoi":"10.21203/rs.3.rs-7961105/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7961105/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e As a natural compound present in a variety of plants, hispidulin has an inhibitory effect on tumors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e In this study, we combined network pharmacology, bioinformatics methods and experimental verification to explore the potential targets of hispidulin in inhibiting hepatocellular carcinoma.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e The network pharmacology analysis showed that the pharmacokinetic properties of hispidulin conformed to the Lipinski's five rules, and it had no hepatotoxicity, carcinogenicity, cytotoxicity, immunotoxicity, mutagenicity, and had the potential to be developed as a drug. The results of network pharmacology and bioinformatics analysis showed that hispidulin may interfere with the occurrence and progression of hepatocellular carcinoma by affecting CDK1, SRC, CCNB1, AURKB and PI3K-AKT signaling pathways. In vitro, hispidulin can inhibit the growth of hepatocellular carcinoma, induce apoptosis and inhibit migration of hepatocellular carcinoma cells. Down-regulate the expression of CDK1, CCNB1, SRC, AURKB protein and weaken the PI3K-AKT pathway signal. It has no obvious toxicity to normal liver cells.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eHispidin can inhibit the occurrence and progression of hepatocellular carcinoma through multiple targets, showing good anti-tumor efficacy in vitro, and has the potential to develop new therapeutic drugs for hepatocellular carcinoma.\u003c/p\u003e","manuscriptTitle":"Mechanistic insights and therapeutic potential of hispidulin in hepatocellular carcinoma: a bioinformatics and experimental study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-28 16:44:46","doi":"10.21203/rs.3.rs-7961105/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":"63492d1d-94b3-4dff-ae80-e2927281405b","owner":[],"postedDate":"October 28th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-27T11:12:41+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-28 16:44:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7961105","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7961105","identity":"rs-7961105","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}