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
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 in...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-024-83900-8 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832585837930348544 |
|---|---|
| author | Khalid Saad Alharbi Muhammad Afzal Fahad A. Al-Abbasi Ehssan Moglad Salwa D. Al-Qahtani Naif A. R. Almalki Faisal Imam Nadeem Sayyed Imran Kazmi |
| author_facet | Khalid Saad Alharbi Muhammad Afzal Fahad A. Al-Abbasi Ehssan Moglad Salwa D. Al-Qahtani Naif A. R. Almalki Faisal Imam Nadeem Sayyed Imran Kazmi |
| author_sort | Khalid Saad Alharbi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-3937cc68eb3341008ecbd3cce4804a2c |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-3937cc68eb3341008ecbd3cce4804a2c2025-01-26T12:26:33ZengNature PortfolioScientific Reports2045-23222025-01-0115112410.1038/s41598-024-83900-8In vivo and in silico study of europinidin against streptozotocin-isoproterenol-induced myocardial damage via alteration of hs-CRP/CPK-MB/Caspase-3/Bcl-2 pathwaysKhalid Saad Alharbi0Muhammad Afzal1Fahad A. Al-Abbasi2Ehssan Moglad3Salwa D. Al-Qahtani4Naif A. R. Almalki5Faisal Imam6Nadeem Sayyed7Imran Kazmi8Department of Pharmacology and Toxicology, College of Pharmacy, Qassim UniversityDepartment of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical CollegeDepartment of Biochemistry, Faculty of Sciences, King Abdulaziz UniversityDepartment of Pharmaceutics, College of Pharmacy, Prince Sattam bin Abdulaziz UniversityDepartment of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah UniversityDepartment of Biochemistry, Faculty of Sciences, King Abdulaziz UniversityDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud UniversitySchool of Pharmacy, Glocal UniversityDepartment of Biochemistry, Faculty of Sciences, King Abdulaziz UniversityAbstract 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.https://doi.org/10.1038/s41598-024-83900-8EuropinidinDiabetesMyocardial infarctionIsoproterenolStreptozotocinDocking study |
| spellingShingle | Khalid Saad Alharbi Muhammad Afzal Fahad A. Al-Abbasi Ehssan Moglad Salwa D. Al-Qahtani Naif A. R. Almalki Faisal Imam Nadeem Sayyed Imran Kazmi 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 Scientific Reports Europinidin Diabetes Myocardial infarction Isoproterenol Streptozotocin Docking study |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Europinidin Diabetes Myocardial infarction Isoproterenol Streptozotocin Docking study |
| url | https://doi.org/10.1038/s41598-024-83900-8 |
| work_keys_str_mv | AT khalidsaadalharbi invivoandinsilicostudyofeuropinidinagainststreptozotocinisoproterenolinducedmyocardialdamageviaalterationofhscrpcpkmbcaspase3bcl2pathways AT muhammadafzal invivoandinsilicostudyofeuropinidinagainststreptozotocinisoproterenolinducedmyocardialdamageviaalterationofhscrpcpkmbcaspase3bcl2pathways AT fahadaalabbasi invivoandinsilicostudyofeuropinidinagainststreptozotocinisoproterenolinducedmyocardialdamageviaalterationofhscrpcpkmbcaspase3bcl2pathways AT ehssanmoglad invivoandinsilicostudyofeuropinidinagainststreptozotocinisoproterenolinducedmyocardialdamageviaalterationofhscrpcpkmbcaspase3bcl2pathways AT salwadalqahtani invivoandinsilicostudyofeuropinidinagainststreptozotocinisoproterenolinducedmyocardialdamageviaalterationofhscrpcpkmbcaspase3bcl2pathways AT naifaralmalki invivoandinsilicostudyofeuropinidinagainststreptozotocinisoproterenolinducedmyocardialdamageviaalterationofhscrpcpkmbcaspase3bcl2pathways AT faisalimam invivoandinsilicostudyofeuropinidinagainststreptozotocinisoproterenolinducedmyocardialdamageviaalterationofhscrpcpkmbcaspase3bcl2pathways AT nadeemsayyed invivoandinsilicostudyofeuropinidinagainststreptozotocinisoproterenolinducedmyocardialdamageviaalterationofhscrpcpkmbcaspase3bcl2pathways AT imrankazmi invivoandinsilicostudyofeuropinidinagainststreptozotocinisoproterenolinducedmyocardialdamageviaalterationofhscrpcpkmbcaspase3bcl2pathways |