Specnuezhenide from Ligustrum sinense Lour. inhibits liver cancer by suppressing glycolysis: a multi-omics study

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This preprint investigates the anti-liver cancer mechanism of Ligustrum sinense (XDQ), an ethnomedicine, using multi-omics analyses in H22 tumor-bearing mice alongside network pharmacology, transcriptomics, and proteomics. XDQ significantly inhibited tumor growth (up to 79.64%) without observable toxicity, and UPLC-Q/TOF-MS identified 66 XDQ compounds, with five including specnuezhenide detected in both serum and tumor tissues, indicating bioavailability. Integrated analyses converged on suppression of glycolysis, showing downregulation of glycolytic enzymes (GPI, PGAM1, PGK1, PKM2), reduced glucose consumption and lactate production, and molecular docking implicating specnuezhenide as a strong binder to GPI, with in vitro confirmation in liver cancer cells. A major caveat is that the work is a preprint and not peer reviewed. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract This study investigates the anti-liver cancer mechanism of Ligustrum sinense Lour. (XDQ), a Tujia ethnomedicine, using a multi-omics approach. In H22 tumor-bearing mice, XDQ significantly inhibited tumor growth by up to 79.64% without observable toxicity. UPLC-Q/TOF-MS analysis identified 66 compounds in XDQ, with five—specnuezhenide, prosapogenin A, oleuropein, oxyberberine, and pseudoanisatin—detected in both serum and tumor tissues, indicating good bioavailability. Integrated network pharmacology, transcriptomics, and proteomics analyses consistently revealed that XDQ's anti-tumor effect is mediated through the suppression of glycolysis. This was evidenced by the downregulation of key glycolytic enzymes, including GPI, PGAM1, PGK1, and PKM2, and a subsequent decrease in glucose consumption and lactate production. Molecular docking identified specnuezhenide as the component with the strongest binding affinity to the rate-limiting enzyme GPI. In vitro validation confirmed that specnuezhenide inhibits glycolysis and suppresses the expression of glycolysis enzymes in liver cancer cells. Our findings demonstrate that XDQ exerts its anti-liver cancer effects primarily by inhibiting tumor glycolysis, with specnuezhenide being a key active constituent, providing a scientific basis for developing XDQ as a potential therapeutic agent.
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Specnuezhenide from Ligustrum sinense Lour. inhibits liver cancer by suppressing glycolysis: a multi-omics 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 Article Specnuezhenide from Ligustrum sinense Lour. inhibits liver cancer by suppressing glycolysis: a multi-omics study Zongchao Hong, Jingxin Yang, Wanjin Sun, Chenhuan Jin, Baodan Hu, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8455901/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 This study investigates the anti-liver cancer mechanism of Ligustrum sinense Lour. (XDQ), a Tujia ethnomedicine, using a multi-omics approach. In H22 tumor-bearing mice, XDQ significantly inhibited tumor growth by up to 79.64% without observable toxicity. UPLC-Q/TOF-MS analysis identified 66 compounds in XDQ, with five—specnuezhenide, prosapogenin A, oleuropein, oxyberberine, and pseudoanisatin—detected in both serum and tumor tissues, indicating good bioavailability. Integrated network pharmacology, transcriptomics, and proteomics analyses consistently revealed that XDQ's anti-tumor effect is mediated through the suppression of glycolysis. This was evidenced by the downregulation of key glycolytic enzymes, including GPI, PGAM1, PGK1, and PKM2, and a subsequent decrease in glucose consumption and lactate production. Molecular docking identified specnuezhenide as the component with the strongest binding affinity to the rate-limiting enzyme GPI. In vitro validation confirmed that specnuezhenide inhibits glycolysis and suppresses the expression of glycolysis enzymes in liver cancer cells. Our findings demonstrate that XDQ exerts its anti-liver cancer effects primarily by inhibiting tumor glycolysis, with specnuezhenide being a key active constituent, providing a scientific basis for developing XDQ as a potential therapeutic agent. Biological sciences/Biochemistry Biological sciences/Cancer Biological sciences/Computational biology and bioinformatics Biological sciences/Drug discovery Ligustrum sinense Lour. Liver cancer Glycolysis Specnuezhenide Full Text Additional Declarations No competing interests reported. Supplementary Files TableS1Reagentmaterials.doc TableS2Thetop1000livercancerrelatedtargets.xlsx TableS357predictedtargetsfor5compounds..xlsx TableS4Recordoftumorvolumeintumorbearingmice.xlsx TableS5Recordoftumorweightintumorbearingmice.xlsx SupplementarymaterialWBrepeats.pdf 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. 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