PROTECTIVE EFFECTS OF CORCHORUS OLITORIUS LEAF EXTRACT AND FRACTIONS AGAINST ISOPROTERENOL-INDUCED ACUTE MYOCARDIAL INFARCTION IN WISTAR RATS.

Abstract

Acute Myocardial Infarction (AMI) is a leading cause of death associated with Heart Failure (HF) worldwide. Oxidative stress, inflammation and apoptosis are important underlying pathogenesis of AMI, which are not target of currently available drugs. Corchorus olitoriusleaf (COL) is useful in ethnomedicine to treat HF. However, there is paucity of scientific information on its effects on AMI. Therefore, the protective effects of COL extract and fractions against isoproterenol-induced AMI in Wistar rats were evaluated.

Corchorus olitorius leaf (COL) was obtained from Moniya market, Ibadan and authenticated at Forestry Research Institute of Nigeria (FHI; 110410). Air-dried COL was extracted with 70% ethanol (COE), concentrated and partitioned with N-hexane (COhex), dichloromethane (CODCM), ethyl acetate (COEtOAc) and ethanol (COEtOH) resulting in four fractions.Isoproterenol (100 mg/kg, i.p) was used to induce AMI in rats. Thirty-five animals (n=7) were pre-treated orally for nineteen days with; distilled water (1.0 mL/kg/day, non-AMI control), distilled water (1.0 mL/kg/day, AMI control), COE (250 and 500 mg/kg/day) or enalapril (10 mg/kg/day) before induction of AMI on days 20 and 21. Another 11 groups of rats (n=6) were pre-treated for twelve days with the four fractions; COhex, CODCM, COEtOAc and COEtOH (50 and 100 mg/kg/day), distilled water and enalapril before induction of AMI on days 13 and 14. Blood volume (BV) and flow (BF) were measured using tail cuff with QRS- and p-interval determined electrocardiographically. Thereafter, serum biomarkers of inflammation: advance oxidised protein product (AOPP), myeloperoxidase (MPO), C-reactive protein (CRP), creatine kinase-MB (CKMB), lactate dehydrogenase (LDH), nitrite and cardiac markers of oxidative stress (malondialdehyde, reduced glutathione and non-protein thiol (NPT) were determined using standard techniques. Nuclear Factor-kB (p65NFKappaB), Bcl-2 protein, Bax protein and p53 expression were determined using immunohistochemistry. Constituents of CODCM were identified using GC-MS. Data were analysed using descriptive statistics and ANOVA at α0.05

The AMI increased QRS interval (21.0±1.0m/s vs 13.0±0.5m/s), reduced p-interval (12.0±0.5m/s vs 21.0±0.5m/s), BF (1.4±0.3cm/s vs 32.0±0.5cm/s) and BV (25.0±1.0m/s vs 107.0±2.0m/s) compared to non-AMI control. The COE (250 mg/kg and 500 mg/kg) and enalapril reduced the interval of QRS (12.0±0.5m/s, 15.0±0.3m/s, 15.4±0.4m/s), increased p-interval (19.2±1.6, 19.2±0.6, 22.8±0.5m/s), enhanced BF (17.0±1.1cm/s, 8.0±0.4cm/s, 12.0±0.7cm/s) and BV (57.0±3.2m/s, 30.0±3.3m/s, 16.0±1.6m/s) significantly compared to AMI. There was a significant increase in nitrite, GSH, NPT in AMI rats compared to normal control, however, COE reversed it. The COE also prevented the increase in serum level of LDH, AOPP, MPO and malondialdehyde. Compared to AMI rats, COE fractions reduced serum level of CRP, CK-MB and tissue level of p53 and increased the expressions of p65NF-KappaB. The CODCM (50 & 100 mg/kg) and enalapril (10 mg/kg) decreased tissue expression of Bax and increased Bcl-2 expression (Bax; 1.00±0.01, 1.00±0.01, 1.00±0.01 vs 16.00±0.05 and Bcl-2; 8.00±0.01, 4.00±0.01, 5.00±0.01 vs 1.00±0.05). The highest activity was observed in CODCM fraction. Cystamine, 3-methoxyflavone were major components.

The protective effects of Corchorus olitorius against acute myocardial infarction in rats may be through modulation of thiol-related antioxidants and p65NFKappaB-dependent antiapoptotic pathways.