{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:12:20Z","timestamp":1760112740102,"version":"build-2065373602"},"reference-count":52,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T00:00:00Z","timestamp":1723075200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Diabetic cardiomyopathy (DCM) poses a significant risk for heart failure in individuals with diabetes, yet its underlying mechanisms remain incompletely understood. Elevated blood sugar levels initiate harmful processes, including apoptosis, collagen accumulation, and fibrosis in the heart. Vinpocetine, a derivative of Vinca minor L., has demonstrated diverse pharmacological effects, including vasodilation, anti-inflammatory properties, and enhanced cellular metabolism. This study aims to investigate Vinpocetine\u2019s protective and remodeling effects in diabetic cardiomyopathy by evaluating biochemical and histopathological parameters. Methods: Twenty-one adult male Wistar rats were induced with diabetes using streptozocin and divided into Diabetes and Diabetes + Vinpocetine groups. Histopathological analyses, TGF-\u03b21 immunoexpression, and measurements of plasma markers (TGF-\u03b2, pro-BNP, Troponin T) were performed. Biochemical analyses included HIF-1 alpha and neuregulin-1\u03b2 quantification and evaluation of lipid peroxidation. Results: Vinpocetine significantly reduced cardiac muscle thickness, TGF-\u03b21 expression, and plasma in diabetic rats. HIF-1 alpha and neuregulin-1\u03b2 levels increased with Vinpocetine treatment. Histopathological observations confirmed reduced fibrosis and structural abnormalities in Vinpocetine-treated hearts. Conclusions: This study provides comprehensive evidence supporting the protective effects of Vinpocetine against diabetic cardiomyopathy. Vinpocetine treatment improved cardiac morphology, immunohistochemistry, and modulation of biochemical markers, suggesting its potential as a therapeutic intervention to attenuate the negative impact of diabetes on heart function.<\/jats:p>","DOI":"10.3390\/jcm13164637","type":"journal-article","created":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T07:01:25Z","timestamp":1723100485000},"page":"4637","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Demonstration of the Protective Effect of Vinpocetine in Diabetic Cardiomyopathy"],"prefix":"10.3390","volume":"13","author":[{"given":"Demet","family":"Erciyes","sequence":"first","affiliation":[{"name":"Department of Cardiology, Faculty of Medicine, Demiro\u011flu Bilim University, 34394 Istanbul, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2448-2337","authenticated-orcid":false,"given":"Ejder Saylav","family":"Bora","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Faculty of Medicine, Izmir Katip \u00c7elebi University, 35620 Izmir, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mustafa Agah","family":"Tekindal","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences Biostatistics, Faculty of Medicine, \u0130zmir Katip \u00c7elebi Un\u0131versity, 35620 Izmir, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oytun","family":"Erba\u015f","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Demiro\u011flu Bilim University, 34394 Istanbul, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1161\/CIRCRESAHA.117.311586","article-title":"Diabetic cardiomyopathy: An update of mechanisms contributing to this clinical entity","volume":"122","author":"Jia","year":"2018","journal-title":"Circ. Res."},{"key":"ref_2","unstructured":"Hayat, M.A. (2014). Chapter 7-Treatment of Diabetic Cardiomyopathy through Upregulating Autophagy by Stimulating AMP-Activated Protein Kinase. Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging, Academic Press."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s10741-016-9536-9","article-title":"The fibrosis-cell death axis in heart failure","volume":"21","author":"Piek","year":"2016","journal-title":"Heart Fail. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s11154-010-9131-7","article-title":"Diabetic cardiomyopathy, causes and effects","volume":"11","author":"Boudina","year":"2010","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/bs.pmbts.2022.07.008","article-title":"Chapter Fourteen-Endocytosis of LXRs: Signaling in liver and disease","volume":"Volume 194","author":"Mani","year":"2023","journal-title":"Progress in Molecular Biology and Translational Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1900\/RDS.2006.3.108","article-title":"Causes and characteristics of diabetic cardiomyopathy","volume":"3","author":"Wang","year":"2006","journal-title":"Rev. Diabet. Stud."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.jdiacomp.2007.12.005","article-title":"Diabetic myocardial disease: Pathophysiology, early diagnosis and therapeutic options","volume":"23","author":"Mytas","year":"2009","journal-title":"J. Diabetes Complicat."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/nrendo.2015.216","article-title":"Insulin resistance and hyperinsulinaemia in diabetic cardiomyopathy","volume":"12","author":"Jia","year":"2016","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_9","first-page":"42726","article-title":"Alkaloid esters. Ger. Offen. 2253750","volume":"79","author":"Lorincz","year":"1973","journal-title":"Chem. Abstr."},{"key":"ref_10","first-page":"1984","article-title":"Ethyl apovincaminate therapy in neurovascular diseases","volume":"26","author":"Szobor","year":"1976","journal-title":"Arzneimittelforschung"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/S1734-1140(11)70574-6","article-title":"Role of Vinpocetine in cerebrovascular diseases","volume":"63","author":"Patyar","year":"2011","journal-title":"Pharmacol. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"335","DOI":"10.3390\/molecules20010335","article-title":"Anti-inflammatory effects of Vinpocetine in atherosclerosis and ischemic stroke: A review of the literature","volume":"20","author":"Zhang","year":"2015","journal-title":"Molecules"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Bora, S., Erdogan, M.A., Armagan, G., Sevgili, E., and Dagc\u0131, T. (2017). Erratum to: Vinpocetine and Vasoactive Intestinal Peptide Attenuate Manganese-Induced Toxicity in NE-4C Cells. Biol. Trace Elem. Res., 175.","DOI":"10.1007\/s12011-016-0775-3"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2338","DOI":"10.1161\/hc4401.098432","article-title":"Upregulation of phosphodiesterase 1A1 expression is associated with the development of nitrate tolerance","volume":"104","author":"Kim","year":"2001","journal-title":"Circulation"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1124\/jpet.112.195446","article-title":"Vinpocetine suppresses pathological vascular remodeling by inhibiting vascular smooth muscle cell proliferation and migration","volume":"343","author":"Cai","year":"2012","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.bbrc.2013.03.092","article-title":"Vinpocetine attenuates lipid accumulation and atherosclerosis formation","volume":"434","author":"Cai","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Wang, Y., Wei, J., Zhang, P., Zhang, X., Wang, Y., Chen, W., Zhao, Y., and Cui, X. (2022). Neuregulin-1, a potential therapeutic target for cardiac repair. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.945206"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1146\/annurev-physiol-021113-170322","article-title":"Hypoxia-inducible factor 1 and cardiovascular disease","volume":"76","author":"Semenza","year":"2014","journal-title":"Annu. Rev. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.yjmcc.2010.10.033","article-title":"Transforming growth factor (TGF)-\u03b2 signaling in cardiac remodeling","volume":"51","author":"Dobaczewski","year":"2011","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"9795","DOI":"10.1073\/pnas.0914414107","article-title":"Vinpocetine inhibits NF-kappaB-dependent inflammation via an IKK-dependent but PDE-independent mechanism","volume":"107","author":"Jeon","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Baeza, C., Pintor-Chocano, A., Carrasco, S., Sanz, A., Ortiz, A., and Sanchez-Ni\u00f1o, M.D. (2024). Paricalcitol Has a Potent Anti-Inflammatory Effect in Rat Endothelial Denudation-Induced Intimal Hyperplasia. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25094814"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Zhuang, J., Peng, W., Li, H., Lu, Y., Wang, K., Fan, F., Li, S., and Xu, Y. (2013). Inhibitory effects of vinpocetine on the progression of atherosclerosis are mediated by Akt\/NF-\u03baB dependent mechanisms in apoE-\/- mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082509"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/0002-9149(74)90089-7","article-title":"Role of diabetes in congestive heart failure; the Framingham study","volume":"34","author":"Kannel","year":"1974","journal-title":"Am. J. Cardiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/0022-2828(81)90318-7","article-title":"Depressed cardiac sarcoplasmic reticular function from diabetic rats","volume":"13","author":"Penpargkul","year":"1981","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.ejphar.2016.06.042","article-title":"The protective role of neuregulin-1: A potential therapy for sepsis-induced cardiomyopathy","volume":"788","author":"Zhou","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1093\/cvr\/cvq316","article-title":"Acute cardiac effects of neuregulin-1\/ErbB signalling","volume":"88","author":"Rochais","year":"2010","journal-title":"Cardiovasc. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/j.cardfail.2017.08.456","article-title":"Chronic Neuregulin-1\u03b2 Treatment Mitigates the Progression of Postmyocardial Infarction Heart Failure in the Setting of Type 1 Diabetes Mellitus by Suppressing Myocardial Apoptosis, Fibrosis, and Key Oxidant-Producing Enzymes","volume":"23","author":"Gupte","year":"2017","journal-title":"J. Card. Fail."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1093\/cvr\/cvm035","article-title":"Complete loss of ischaemic preconditioning-induced cardioprotection in mice with partial deficiency of HIF-1 alpha","volume":"77","author":"Cai","year":"2008","journal-title":"Cardiovasc. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1016\/j.bbrc.2011.12.115","article-title":"Effect of hypoxia-inducible factor 1-alpha on hypoxia\/reoxygenation-induced apoptosis in primary neonatal rat cardiomyocytes","volume":"417","author":"Wang","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"09603271221136209","DOI":"10.1177\/09603271221136209","article-title":"Phosphodiesterase inhibitor, Vinpocetine, guards against doxorubicin induced cardiotoxicity via modulation of HIF\/VEGF and cGMP\/cAMP\/SIRT signaling pathways","volume":"41","author":"Refaie","year":"2022","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e010243","DOI":"10.1161\/CIRCOUTCOMES.123.010243","article-title":"Role of Biomarkers of Myocardial Injury to Predict Adverse Outcomes in Hypertrophic Cardiomyopathy","volume":"17","author":"Zhang","year":"2024","journal-title":"Circ. Cardiovasc. Qual. Outcomes"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Hosseini, A., Ghorbani, A., Alavi, M.S., Forouhi, N., Rajabian, A., Boroumand-Noughabi, S., Sahebkar, A., and Eid, A.H. (2023). Cardioprotective effect of Sanguisorba minor against isoprenaline-induced myocardial infarction in rats. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1305816"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.18632\/oncotarget.22879","article-title":"Troponin through the looking-glass: Emerging roles beyond regulation of striated muscle contraction","volume":"9","author":"Johnston","year":"2017","journal-title":"Oncotarget"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1002\/jat.3974","article-title":"Molecular biomarkers of cantharidin-induced cardiotoxicity in Sprague-Dawley rats: Troponin T, vascular endothelial growth factor and hypoxia inducible factor-1\u03b1","volume":"40","author":"Youyou","year":"2020","journal-title":"J. Appl. Toxicol."},{"key":"ref_36","first-page":"4403","article-title":"Cardio-protective effect of dapagliflozin against doxorubicin-induced cardiomyopathy in rats","volume":"26","author":"Belen","year":"2022","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1093\/eurheartj\/ehac779.044","article-title":"Estimation of brain natriuretic peptide values from N-terminal pro-brain natriuretic peptide levels and other factors","volume":"44","author":"Kajikawa","year":"2023","journal-title":"Eur. Heart J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.phrs.2015.12.032","article-title":"Higenamine protects ischemia\/reperfusion induced cardiac injury and myocyte apoptosis through activation of beta2-AR\/PI3K\/AKT signaling pathway","volume":"104","author":"Wu","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1006\/mgme.2000.3032","article-title":"Induction of cardiac fibrosis by transforming growth factor-beta(1)","volume":"71","author":"Lijnen","year":"2000","journal-title":"Mol. Genet. Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1007\/s00395-011-0228-2","article-title":"Cyclic nucleotide phosphodiesterase 1A: A key regulator of cardiac fibroblast activation and extracellular matrix remodeling in the heart","volume":"106","author":"Miller","year":"2011","journal-title":"Basic Res. Cardiol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Chen, S., Knight, W., and Yan, C. (2018). Roles of PDE1 in Pathological Cardiac Remodeling and Dysfunction. J. Cardiovasc. Dev. Dis., 5.","DOI":"10.3390\/jcdd5020022"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"817.12","DOI":"10.1096\/fasebj.2019.33.1_supplement.817.12","article-title":"PDE1 Inhibition Attenuates Doxorubicin-Induced Toxicity in Primary Mouse Cardiomyocytes","volume":"33","author":"Vigneshwar","year":"2019","journal-title":"FASEB J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"119857","DOI":"10.1016\/j.lfs.2021.119857","article-title":"Cardiac phosphodiesterases are differentially increased in diabetic cardiomyopathy","volume":"283","author":"Hanna","year":"2021","journal-title":"Life Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.ejphar.2017.11.041","article-title":"An update on Vinpocetine: New discoveries and clinical implications","volume":"819","author":"Zhang","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.cardiores.2004.04.030","article-title":"TGF-beta1 and angiotensin networking in cardiac remodeling","volume":"63","author":"Rosenkranz","year":"2004","journal-title":"Cardiovasc. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.cardiores.2007.06.022","article-title":"Functional, structural and molecular aspects of diastolic heart failure in the diabetic (mRen-2)27 rat","volume":"76","author":"Connelly","year":"2007","journal-title":"Cardiovasc. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1253\/circj.CJ-13-1564","article-title":"Diabetes-related heart failure","volume":"78","author":"Fein","year":"2014","journal-title":"Circ. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.yjmcc.2021.06.003","article-title":"Epigenetic alterations of TGF\u03b2 and its main canonical signaling mediators in the context of cardiac fibrosis","volume":"159","author":"Algeciras","year":"2021","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_49","first-page":"1159","article-title":"Cardiac pathology in the hypertensive diabetic rat. Biventricular damage with right ventricular predominance","volume":"134","author":"Fein","year":"1989","journal-title":"Am. J. Pathol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1172\/JCI114734","article-title":"Abnormal cardiac function in the streptozotocin-diabetic rat. Changes in active and passive properties of the left ventricle","volume":"86","author":"Litwin","year":"1990","journal-title":"J. Clin. Investig."},{"key":"ref_51","first-page":"408","article-title":"Evaluation of Cardioprotective Role of Vinpocetine in Isoproterenol-induced Myocardial Infarction in Rats","volume":"9","author":"Haque","year":"2015","journal-title":"J. Pharm. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1161\/CIRCULATIONAHA.119.039767","article-title":"Endothelial Forkhead Box Transcription Factor P1 Regulates Pathological Cardiac Remodeling through Transforming Growth Factor-\u03b21\u2013Endothelin-1 Signal Pathway","volume":"140","author":"Liu","year":"2019","journal-title":"Circulation"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/16\/4637\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:31:54Z","timestamp":1760110314000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/16\/4637"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,8]]},"references-count":52,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["jcm13164637"],"URL":"https:\/\/doi.org\/10.3390\/jcm13164637","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2024,8,8]]}}}