WITHDRAWN: 6-Gingerol ameliorates myocardial injury and lipid accumulation in diabetic mice: Associating with modulating ACSL3/ACSL4 expression and AMPK/Nrf2/SLC7A11 pathway activation to inhibit ferroptosis

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Abstract Background To investigate the protective effects and mechanisms of 6-gingerol(6-G) on myocardial injury in diabetic mice. Methods In vivo , 18-week-old db/db mice were treated with 6-G by gavage once daily for 8 weeks. Myocardial pathological changes were assessed by H&E, WGA, Masson, Sirius red and ORO staining. In vitro , HL-1 cells were treated with high glucose and high fatty acid (HGHF) for 24 hours with or without 6-G administration. UID RNA-seq was employed to explore the protective mechanism of 6-G. ROS, MDA, GSH and SOD were examined. The expression of fatty acid transporters and ferroptosis-related proteins and genes was detected by qRT-PCR and WB. Results Myocardial injury and lipid accumulation were mitigated by 6-G. The expression of fatty acid transporters including CD36, FATP1 and FABP3 was downregulated by 6-G. Similarly, the intracellular lipid levels and the expression of CD36 and FABP3 in HL-1 cells treated with HGHF were attenuated by 6-G. UID RNA-seq analysis reveal that the protective mechanism of 6-G is associated with the AMPK pathway and ferroptosis. After 6-G treatment, the levels of ROS and MDA decreased, whereas the levels of SOD and GSH in the hearts of db/db mice. 6-G enhanced AMPK activation and upregulated the expression of Nrf2, SLC7A11 and GPX4 both in vivo and in vitro . Both ACSL3 underexpression and overexpressed ACSL4 overexpression in the model group were reversed by 6-G treatment. The protective effect and upregulation of Nrf2, SLC7A11 and GPX4 were abolished by compound C. Conclusion 6-G mitigates myocardial injury and inhibits ferroptosis via ACSL3/ACSL4 regulation and AMPK/Nrf2/SLC7A11 pathway activation.
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WITHDRAWN: 6-Gingerol ameliorates myocardial injury and lipid accumulation in diabetic mice: Associating with modulating ACSL3/ACSL4 expression and AMPK/Nrf2/SLC7A11 pathway activation to inhibit ferroptosis | 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 WITHDRAWN: 6-Gingerol ameliorates myocardial injury and lipid accumulation in diabetic mice: Associating with modulating ACSL3/ACSL4 expression and AMPK/Nrf2/SLC7A11 pathway activation to inhibit ferroptosis Renjie Qin, Xin Zeng, Ling Yuan, Meng Wang, Hongyu Luo, Chendan Deng, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6388897/v2 This work is licensed under a CC BY 4.0 License Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Editorial Note The full text of this preprint has been withdrawn, as it was submitted in error. Therefore, the authors do not wish this work to be cited as a reference. Questions should be directed to the corresponding author. Editorial notes are used to provide important context regarding the topic of a preprint or to alert readers to potential issues concerning that preprint or a downstream publication associated with it. For more information on editorial notes, see our Editorial Policies . Abstract The full text of this preprint has been withdrawn, as it was submitted in error. Therefore, the authors do not wish this work to be cited as a reference. Questions should be directed to the corresponding author. Full Text The authors have withdrawn this preprint from Research Square. Cite Share Download PDF Status: Posted Version 2 posted You are reading this latest preprint version Show more versions 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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