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2000
Volume 17, Issue 1
  • ISSN: 1874-4672
  • E-ISSN: 1874-4702

Abstract

Background

Diabetic cardiomyopathy (DCM) is a common and severe complication of Diabetes Mellitus (DM). Dihydromyricetin (DHM) is a flavonoid compound with potential cardioprotective effects, but the mechanism of DHM in diabetes-induced myocardial damage and autophagy is not fully understood.

Objective

The objective of this study is to evaluate the effects of DHM on cardiac function and pathological features of DCM, with a particular focus on its impact on the SNHG17/miR-34a/SIDT2 pathway.

Methods

experiments: After constructing the DM mice model, it was treated with different doses of DHM. Masson's staining and collagen deposition/fibrosis markers were used to evaluate the effect of DHM on cardiac fibrosis in DM mice. In experiments: 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry were used to determine the influence of DHM on cell viability and apoptosis, respectively, in high glucose-induced HL-1 cells. Enzyme-labeled Immunosorbent Assay was used to detect levels of cardiac enzyme and inflammation-related factors, while Western blot analyzed the levels of AMPK/mTOR and autophagy-related proteins.

Results

DHM significantly improved cardiac function in DM and reduced Renin-angiotensin-aldosterone system markers, alongside decreasing markers of cardiomyocyte damage. DHM mitigated myocardial fibrosis, inflammatory marker levels, and autophagy dysregulation while upregulating lncRNA expression. Mechanistically, DHM acted through the /miR-34a/SID1 transmembrane family member 2 () axis, reducing miR-34a expression and restoring SIDT2-mediated autophagy balance, ultimately alleviating apoptosis, inflammation, and fibrosis in diabetic cardiac tissue and high-glucose-induced HL-1 cells.

Conclusion

DHM improves cardiac function and mitigates DCM progression by targeting the /miR-34a/ regulatory axis, thereby reducing inflammation, fibrosis, and autophagy dysregulation. These findings provide mechanistic insights into DHM’s cardioprotective effects, supporting its potential as a therapeutic agent for DCM.

© 2024 The Author(s). Published by Bentham Science Publishers. This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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2024-01-01
2025-09-16
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References

  1. El HayekM.S. ErnandeL. BenitahJ.P. GomezA.M. PereiraL. The role of hyperglycaemia in the development of diabetic cardiomyopathy.Arch. Cardiovasc. Dis.20211141174876010.1016/j.acvd.2021.08.00434627704
    [Google Scholar]
  2. HashemiM. ZandiehM.A. ZiaolhaghS. MojtabaviS. SadiF.H. KoohparZ.K. GhanbariradM. HaghighatfardA. BehroozaghdamM. KhorramiR. NabaviN. RenJ. ReiterR.J. SalimimoghadamS. RashidiM. HushmandiK. TaheriazamA. EntezariM. Nrf2 signaling in diabetic nephropathy, cardiomyopathy and neuropathy: Therapeutic targeting, challenges and future prospective.Biochim. Biophys. Acta Mol. Basis Dis.20231869516671410.1016/j.bbadis.2023.16671437028606
    [Google Scholar]
  3. FarazandehM. MahmoudabadyM. AsghariA.A. NiazmandS. Diabetic cardiomyopathy was attenuated by cinnamon treatment through the inhibition of fibro‐inflammatory response and ventricular hypertrophy in diabetic rats.J. Food Biochem.2022468e1420610.1111/jfbc.1420635474577
    [Google Scholar]
  4. StudnevaI.M. VeselovaO.M. DobrokhotovI.V. SerebryakovaL.I. PalkeevaM.E. MolokoedovA.S. AzmukoA.A. OvchinnikovM.V. SidorovaM.V. PisarenkoO.I. Chimeric agonist of galanin receptor GALR2 reduces heart damage in rats with streptozotocin-induced diabetes.Biochemistry202287434635510.1134/S000629792204004635527373
    [Google Scholar]
  5. ZhuN ZhuL HuangB XiangW ZhaoX. Galectin-3 inhibition ameliorates streptozotocin-induced diabetic cardiomyopathy in mice.Front Cardiovasc Med.2022986837210.3389/fcvm.2022.868372
    [Google Scholar]
  6. AsghariA.A. MahmoudabadyM. ShababS. NiazmandS. Anti-inflammatory, anti-oxidant and anti-apoptotic effects of olive leaf extract in cardiac tissue of diabetic rats.J. Pharm. Pharmacol.202274796197210.1093/jpp/rgac01935551403
    [Google Scholar]
  7. Lorenzo-AlmorósA. Cepeda-RodrigoJ.M. LorenzoÓ. Diabetic cardiomyopathy.Rev. Clin. Esp.2022222210011110.1016/j.rceng.2019.10.01235115137
    [Google Scholar]
  8. ShenX YinF The mechanisms and clinical application of traditional Chinese medicine Lianhua-Qingwen capsule.Biomed Pharmacother.202114211199810.1016/j.biopha.2021.111998
    [Google Scholar]
  9. GaoL. CaoM. LiJ.Q. QinX.M. FangJ. Traditional Chinese medicine network pharmacology in cardiovascular precision medicine.Curr. Pharm. Des.202127262925293310.2174/18734286MTExhNDUh433183189
    [Google Scholar]
  10. CaoL WangX ZhuG LiS WangH WuJ Traditional Chinese medicine therapy for Esophageal cancer: A literature review.Integr Cancer Ther.2021201534735421106172010.1177/15347354211061720
    [Google Scholar]
  11. ZhangH.Y. WangH.L. ZhongG.Y. ZhuJ.X. Molecular mechanism and research progress on pharmacology of traditional Chinese medicine in liver injury.Pharm. Biol.201856159461110.1080/13880209.2018.151718531070528
    [Google Scholar]
  12. LeL JiangB WanW ZhaiW XuL HuK Metabolomics reveals the protective of Dihydromyricetin on glucose homeostasis by enhancing insulin sensitivity.Sci Rep.201663618410.1038/srep36184
    [Google Scholar]
  13. WuJ. XiaoZ. LiH. ZhuN. GuJ. WangW. LiuC. WangW. QinL. Present status, challenges, and prospects of dihydromyricetin in the battle against cancer.Cancers20221414348710.3390/cancers1414348735884547
    [Google Scholar]
  14. KangL. MaX. YuF. XuL. LangL. Dihydromyricetin alleviates non-alcoholic fatty liver disease by modulating gut microbiota and inflammatory signaling pathways.J. Microbiol. Biotechnol.202434122637264710.4014/jmb.2406.0604839639497
    [Google Scholar]
  15. LiuX. WangS. DingC. ZhaoY. ZhangS. SunS. ZhangL. MaS. DingQ. LiuW. Polyvinylpyrrolidone/chitosan-loaded dihydromyricetin-based nanofiber membrane promotes diabetic wound healing by anti-inflammatory and regulating autophagy-associated protein expression.Int. J. Biol. Macromol.2024259Pt 112916010.1016/j.ijbiomac.2023.12916038181908
    [Google Scholar]
  16. HouL. JiangF. HuangB. ZhengW. JiangY. CaiG. LiuD. HuC.Y. WangC. Dihydromyricetin resists inflammation-induced muscle atrophy via ryanodine receptor-CaMKK-AMPK signal pathway.J. Cell. Mol. Med.202125219953997110.1111/jcmm.1681034676967
    [Google Scholar]
  17. XiongX XiaM NiuA ZhangY YinT HuangQ Dihydromyricetin contributes to weight loss via pro-browning mediated by mitochondrial fission in white adipose.Eur J Pharmacol.202293517534510.1016/j.ejphar.2022.175345
    [Google Scholar]
  18. WuX. LiuZ. YuX.Y. XuS. LuoJ. Autophagy and cardiac diseases: Therapeutic potential of natural products.Med. Res. Rev.202141131434110.1002/med.2173332969064
    [Google Scholar]
  19. XueF. ChengJ. LiuY. ChengC. ZhangM. SuiW. ChenW. HaoP. ZhangY. ZhangC. Cardiomyocyte-specific knockout of ADAM17 ameliorates left ventricular remodeling and function in diabetic cardiomyopathy of mice.Signal Transduct. Target. Ther.20227125910.1038/s41392‑022‑01054‑335909160
    [Google Scholar]
  20. GaoF. LiangT. LuY.W. PuL. FuX. DongX. HongT. ZhangF. LiuN. ZhouY. WangH. LiangP. GuoY. YuH. ZhuW. HuX. ChenH. ZhouB. PuW.T. MablyJ.D. WangJ. WangD.Z. ChenJ. Reduced mitochondrial protein translation promotes cardiomyocyte proliferation and heart regeneration.Circulation2023148231887190610.1161/CIRCULATIONAHA.122.06119237905452
    [Google Scholar]
  21. YamamotoT. SanoM. Deranged myocardial fatty acid metabolism in heart failure.Int. J. Mol. Sci.202223299610.3390/ijms2302099635055179
    [Google Scholar]
  22. JinN. ZhangM. ZhouL. JinS. ChengH. LiX. ShiY. XiangT. ZhangZ. LiuZ. ZhaoH. XieJ. Mitochondria transplantation alleviates cardiomyocytes apoptosis through inhibiting AMPKα‐mTOR mediated excessive autophagy.FASEB J.20243810e2365510.1096/fj.202400375R38767449
    [Google Scholar]
  23. TuW. LiL. YiM. ChenJ. WangX. SunY. Dapagliflozin attenuates high glucose-and hypoxia/reoxygenation-induced injury via activating AMPK/mTOR-OPA1-mediated mitochondrial autophagy in H9c2 cardiomyocytes.Arch. Physiol. Biochem.2024130664965910.1080/13813455.2023.225220037655809
    [Google Scholar]
  24. PiddingtonR. JoyceJ. DhanasekaranP. BakerL. Diabetes mellitus affects prostaglandin E2 levels in mouse embryos during neurulation.Diabetologia199639891592010.1007/BF004039108858213
    [Google Scholar]
  25. WenJ ZouW WangR LiuH YangY LiH Cardioprotective effects of Aconiti Lateralis Radix Praeparata combined with Zingiberis Rhizoma on doxorubicin-induced chronic heart failure in rats and potential mechanisms.J Ethnopharmacol.2019238111880
    [Google Scholar]
  26. WangJ. YangH. WangC. KanC. Cyp2e1 knockdown attenuates high glucose-induced apoptosis and oxidative stress of cardiomyocytes by activating PI3K/Akt signaling.Acta Diabetol.20236091219122910.1007/s00592‑023‑02110‑237195324
    [Google Scholar]
  27. ZhangM. SuiW. XingY. ChengJ. ChengC. XueF. ZhangJ. WangX. ZhangC. HaoP. ZhangY. Angiotensin IV attenuates diabetic cardiomyopathy via suppressing FoxO1-induced excessive autophagy, apoptosis and fibrosis.Theranostics202111188624863910.7150/thno.4856134522203
    [Google Scholar]
  28. ChangD. XuT.T. ZhangS.J. CaiY. MinS.D. ZhaoZ. LuC.Q. WangY.C. JuS. Telmisartan ameliorates cardiac fibrosis and diastolic function in cardiorenal heart failure with preserved ejection fraction.Exp. Biol. Med.2021246232511252110.1177/1535370221103505834342551
    [Google Scholar]
  29. ShaJ. LiJ. ZhouY. YangJ. LiuW. JiangS. WangY. ZhangR. DiP. LiW. The p53/p21/p16 and PI3K /Akt signaling pathways are involved in the ameliorative effects of maltol on D‐galactose‐induced liver and kidney aging and injury.Phytother. Res.20213584411442410.1002/ptr.714234028092
    [Google Scholar]
  30. WuM.X. WangS.H. XieY. ChenZ.T. GuoQ. YuanW.L. GuanC. XuC.Z. HuangY.N. WangJ.F. ZhangH.F. ChenY.X. Interleukin-33 alleviates diabetic cardiomyopathy through regulation of endoplasmic reticulum stress and autophagy via insulin-like growth factor-binding protein 3.J. Cell. Physiol.202123664403441910.1002/jcp.3015833184863
    [Google Scholar]
  31. LiuX. JiangL. LiY. HuangY. HuX. ZhuW. WangX. WuY. MengX. QiX. Wogonin protects glomerular podocytes by targeting Bcl-2-mediated autophagy and apoptosis in diabetic kidney disease.Acta Pharmacol. Sin.20224319611010.1038/s41401‑021‑00721‑534253875
    [Google Scholar]
  32. LiA. YiB. HanH. YangS. HuZ. ZhengL. WangJ. LiaoQ. ZhangH. Vitamin D-VDR (vitamin D receptor) regulates defective autophagy in renal tubular epithelial cell in streptozotocin-induced diabetic mice via the AMPK pathway.Autophagy202218487789010.1080/15548627.2021.196268134432556
    [Google Scholar]
  33. HanR.H. HuangH.M. HanH. ChenH. ZengF. XieX. LiuD.Y. CaiY. ZhangL.Q. LiuX. XiaZ.Y. TangJ. Propofol postconditioning ameliorates hypoxia/reoxygenation induced H9c2 cell apoptosis and autophagy via upregulating forkhead transcription factors under hyperglycemia.Mil. Med. Res.2021815810.1186/s40779‑021‑00353‑034753510
    [Google Scholar]
  34. ShiY LiH WuT WangQ ZhuQ GuanX Docosahexaenoic acid-enhanced autophagic flux improves cardiac dysfunction after Myocardial infarction by targeting the AMPK/mTOR signaling pathway.Oxid Med Cell Longev.202220221509421
    [Google Scholar]
  35. LiuS. AiQ. FengK. LiY. LiuX. The cardioprotective effect of dihydromyricetin prevents ischemia–reperfusion-induced apoptosis in vivo and in vitro via the PI3K/Akt and HIF-1α signaling pathways.Apoptosis201621121366138510.1007/s10495‑016‑1306‑627738772
    [Google Scholar]
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