Malvidin-3,5-O-diglucoside derived from spine grape (Vitis davidii) inhibits fructose-induced lipid accumulation in HepG2 cells: beneficial effects on MASLD treatment

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Abstract Metabolic dysfunction-associated steatotic liver disease (MASLD) is considered an important independent risk factor for hepatocellular carcinoma (HCC). This study aims to investigate the anti-lipogenic effects and mechanisms of Malvidin-3,5- O -diglucoside (M35G) derived from Vitis davidii on a high-fructose-induced MASLD cell model in HepG2 cells. Through the detection of various physicochemical indicators, histology, free fatty acids and their metabolites, transcription factors, and enzyme expression, it was demonstrated that 10 mM fructose treatment for 72 hours significantly increased lipid accumulation in HepG2 cells. M35G reduced hepatic lipid accumulation and improves FFA metabolism by inhibiting the expression of transcription factors and enzymes involved in de novo lipogenesis (DNL) and promoting the β-oxidation of fatty acids. M35G also ameliorated fructose-induced glucose metabolism disorder by suppressing KHK-c and PEPCK expression while upregulating AMPK and PKM2 expression. This validated the inhibitory role of M35G in mediating the development of fatty liver disease, which may aid in the prevention and treatment of MASLD.
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Malvidin-3,5-O-diglucoside derived from spine grape (Vitis davidii) inhibits fructose-induced lipid accumulation in HepG2 cells: beneficial effects on MASLD treatment | 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 Malvidin-3,5-O-diglucoside derived from spine grape (Vitis davidii) inhibits fructose-induced lipid accumulation in HepG2 cells: beneficial effects on MASLD treatment Tiantian Cheng, Yang Liu, Yifan Wang, Pei Zhao, Xinyuan Ma, Fuliang Han This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7215499/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 29 Oct, 2025 Read the published version in Naunyn-Schmiedeberg's Archives of Pharmacology → Version 1 posted 10 You are reading this latest preprint version Abstract Metabolic dysfunction-associated steatotic liver disease (MASLD) is considered an important independent risk factor for hepatocellular carcinoma (HCC). This study aims to investigate the anti-lipogenic effects and mechanisms of Malvidin-3,5- O -diglucoside (M35G) derived from Vitis davidii on a high-fructose-induced MASLD cell model in HepG2 cells. Through the detection of various physicochemical indicators, histology, free fatty acids and their metabolites, transcription factors, and enzyme expression, it was demonstrated that 10 mM fructose treatment for 72 hours significantly increased lipid accumulation in HepG2 cells. M35G reduced hepatic lipid accumulation and improves FFA metabolism by inhibiting the expression of transcription factors and enzymes involved in de novo lipogenesis (DNL) and promoting the β-oxidation of fatty acids. M35G also ameliorated fructose-induced glucose metabolism disorder by suppressing KHK-c and PEPCK expression while upregulating AMPK and PKM2 expression. This validated the inhibitory role of M35G in mediating the development of fatty liver disease, which may aid in the prevention and treatment of MASLD. Anthocyanins Fructose HepG2 cell Hepatic Steatosis De novo lipogenesis Full Text Additional Declarations No competing interests reported. Supplementary Files supplementaryfile20250424.docx Cite Share Download PDF Status: Published Journal Publication published 29 Oct, 2025 Read the published version in Naunyn-Schmiedeberg's Archives of Pharmacology → Version 1 posted Editorial decision: Revision requested 18 Sep, 2025 Reviews received at journal 17 Sep, 2025 Reviews received at journal 04 Sep, 2025 Reviewers agreed at journal 25 Aug, 2025 Reviewers agreed at journal 22 Aug, 2025 Reviewers agreed at journal 05 Aug, 2025 Reviewers invited by journal 04 Aug, 2025 Editor assigned by journal 30 Jul, 2025 Submission checks completed at journal 30 Jul, 2025 First submitted to journal 25 Jul, 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. 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