EFFECTS OF METHANOL EXTRACT OF Artocarpus altilis (BREADFRUIT) ON ATHEROGENIC INDICES AND REDOX STATUS OF CELLULAR SYSTEM OF HYPERCHOLESTEROLEMIC RATS

Abstract

Hypercholesterolemia is a dominant risk factor for the development of cardiovascular diseases and has become a growing problem globally. Pharmacological interventions for the treatment of hypercholesterolemia involve the use of fibrates, bile acid sequestrants and statins. Due to high prevalence of adverse effects of these drugs, the quest for natural products with hypolipidemic potential is warranted. Artocarpus altilis (Breadfruit) is used locally in the treatment of hypertension. This study was designed to evaluate the effects of Methanol Extract of Artocarpus altilis (MEAA) on atherogenic indices and redox status of rats fed with dietary cholesterol. Studies on MEAA were conducted to determine its free radical scavenging potential. The 2,2-diphenyI-1-picrylhydrazyl (DPPH), nitric oxide (NO), hydrogen peroxide (H₂O₂) and hydroxyl (OH) radicals scavenging effects of MEAA were determined by uv- spectrophotometry. Thirty-five adult male rats (150-200g) were divided into 7 groups of 5 rats each and treated orally with corn oil (control), dietary cholesterol (30mg/0.3mL), MEAA (100mg/kg)+ cholesterol, MEAA (200mg/kg)+cholesterol, questran (0.26g/kg)+cholesterol, questran alone (0.26g/kg) and MEAA alone (200mg/kg) for nine consecutive weeks. Lipid profile - Total Cholesterol (TC), Triglycerides, Low Density Lipoprotein- cholesterol (LDL-C) and High Density Lipoprotein-Cholesterol (LDL-C) were determined spectrophotometrically. Liver function enzymes - Aspartate and Alanine Aminotransferases (AST and ALT) and lactate dehydrogenase (LDH) were assayed by spectrophotometric technique. Antioxidant parameters - reduced glutathione (GSH), glutathione-s-transferase (GST), glutathione peroxidase (GPx), catalase, superoxide dismutase (SOD) and lipid peroxidation (LPO) were estimated by spectroflorometry. Data were analysed using ANOVA and Student's t-test at p=0.05. The methanol extract of Artocarpus altilis effectively scavenged DPPH and OH radicals with lC₅₀ of 593 ug/mL and 487 ug/mL respectively. MEAA significantly scavenged H₂O₂ and NO in a dose-dependent manner. High dietary cholesterol intake caused a significant increase in the levels of serum hepatic and cardiac TC by 110%, 70% and 85%; LDL-C by 79%, 82% and 176%, and TG by 68%, 96% and 62%, respectively. In hypercholesterolemic rats, the serum and cardiac HDL-C levels (150.4±32.5, 347.5±25.0 mg/dL) were significantly lower than the controls (242.1±29.6, 451.2±79.8 mg/dL). Treatment with MEAA (200mg/kg) significantly increased serum and cardiac HDL-C levels (228.5±16.7, 433.0±45.9 mg/dL respectively) relative to hypercholesterolemic. In hypercholesterolemic rats, the levels of LDH, ALT and AST (4890.5±87.6, 121.8 ±19.6 and 362.1±11.0 U/L respectively) and LPO (4.8±0.7 umolMDA/mg protein) were significantly increased relative to controls (1822.8±177.9, 52.1±7.7, 218.0±18.0 U/L) and 1.3±0.2 umoIMDA/mg protein respectively. In contrast, hepatic and cardiac SOD, CAT and GPx were significantly decreased in hypercholesterolemic rats. Treatment with MEAA (200mg/kg) significantly improved the lipid profile and antioxidant indices of hypercholesterolemic rats. The results for MEAA (200mg/kg) were similar with questran treated rats. Methanol extract Artocarpus altilis elicited hypolipidemic effect in hypercholesterolemic rats via mechanism that involves radicals scavenging activities.