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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.

Authors :
Alharbi KS
Afzal M
Al-Abbasi FA
Moglad E
Al-Qahtani SD
Almalki NAR
Imam F
Sayyed N
Kazmi I
Source :
Scientific reports [Sci Rep] 2025 Jan 24; Vol. 15 (1), pp. 3076. Date of Electronic Publication: 2025 Jan 24.
Publication Year :
2025

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).)

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