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In vivo and in silico study of europinidin against streptozotocin-isoproterenol-induced myocardial damage via alteration of hs-CRP/CPK-MB/Caspase-3/Bcl-2 pathways.
In vivo and in silico study of europinidin against streptozotocin-isoproterenol-induced myocardial damage via alteration of hs-CRP/CPK-MB/Caspase-3/Bcl-2 pathways.
- Source :
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Scientific reports [Sci Rep] 2025 Jan 24; Vol. 15 (1), pp. 3076. Date of Electronic Publication: 2025 Jan 24. - Publication Year :
- 2025
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Abstract
- Europinidin is a novel anthocyanidin found in the petals of Plumbago europea that exhibits several physiological effects. Research was conducted to assess europinidin's cardioprotective efficacy in a diabetic and myocardial infarction (MI) experimental model. Rat was injected through the intraperitoneal administration of 45 mg/kg of streptozotocin (STZ), while MI was induced by subcutaneously administering 85 mg/kg of isoproterenol (ISP) at 24 and 48 h prior to the sacrifice procedure. Europinidin 10 and 20 mg/day was administered orally for 4 weeks after validation of diabetes (glucose > 250 mg/dl) on the 7th day. Experimental rats were randomly allocated to control, STZ-ISP control, STZ-ISP + europinidin-10 mg, STZ-ISP + europinidin-20 mg and europinidin 20 mg perse group. Biochemicals parameters including anti-diabetic (Glucose, HbA1c, serum insulin), cardiac markers (hs-CRP, CPK-MB), dyslipidaemia (lipid analysis), anti-inflammatory (IL6, TNF-α and IL-β), oxidative stress (MDA) and antioxidant (SOD, CAT and GSH), kidney function (creatinine), liver function (AST) and pancreatic function (lipase) along with apoptosis markers (Bcl-2, caspase-3) were evaluated. In addition, histopathological indices of heart injury were investigated. In addition, molecular docking (AUTODOCK Tools 1.5.6.) and dynamics were performed. Europinidin (10 and 20 mg/day) reduced blood glucose, HbA1c, hs-CRP, and CPK-MB. It improved serum insulin, blood lipid profile and reduced inflammatory cytokines (IL-6, TNF-α, IL-β), oxidative stress and increased antioxidant enzymes (SOD, CAT and GSH). Europinidin also protected renal, hepatic functions and restored apoptosis markers (increased Bcl-2, decreased caspase-3 levels). Histopathological analysis demonstrated a reduced extent of myocardial necrosis and fibrosis. Europinidin binds in silico to proteins 1NME, 1I0E, 3I2Y and 4AQ3 with energies of -7.038, -6.682, -8.6 and - 8.761 kcal/mol, respectively. While molecular dynamics simulation studies supported the interactions of europinidin with important therapeutic target proteins. Europinidin demonstrates significant cardioprotective and anti-diabetic potential in a diabetic MI experimental model.<br />Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: The animal experiments were approved by the Institutional Ethical Committee of Animals, Trans-Genica Ethical Committee, M.S., India (TRS/PT/23/39/IAEC). In addition, all procedures for animal experiments described in this study were performed in accordance with the IAEC guidelines for the care and use of laboratory animals and ARRIVE guidelines.<br /> (© 2025. The Author(s).)
- Subjects :
- Animals
Rats
Male
C-Reactive Protein metabolism
Myocardial Infarction drug therapy
Myocardial Infarction metabolism
Myocardial Infarction pathology
Creatine Kinase, MB Form blood
Creatine Kinase, MB Form metabolism
Anthocyanins pharmacology
Anthocyanins chemistry
Signal Transduction drug effects
Oxidative Stress drug effects
Myocardium metabolism
Myocardium pathology
Rats, Wistar
Computer Simulation
Cardiotonic Agents pharmacology
Streptozocin
Caspase 3 metabolism
Diabetes Mellitus, Experimental drug therapy
Diabetes Mellitus, Experimental metabolism
Isoproterenol
Proto-Oncogene Proteins c-bcl-2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 39856142
- Full Text :
- https://doi.org/10.1038/s41598-024-83900-8