EFFECTS OF Abrus precatorius (L.) LEAF METHANOL EXTRACT ON HIGH FAT DIET-INDUCED OXIDATIVE STRESS, INFLAMMATION AND DYSLIPIDEMIA IN MALE WISTAR RATS

Abstract

ABSTRACT Abrus precatorius leaf is widely used for tradomedicinal purposes in treating myriads of diseases. However, there is a paucity of information on its pharmacological mechanism of action on such diseases. The present study investigated the antioxidative, anti-inflammatory and antidyslipidemic effects of A. precatorius leaf methanol extract (APLME) on high-fat diet (HFD)-induced dyslipidemic male Wistar rats. Seventy male Wistar rats (280 - 300) g were separated into seven groups (n = 6): group 1 (control); group 2 (HFD); group 3 (HFD + standard drug, 7.2 mg/kg atorvastatin p.o.); group 4 (HFD + 150 mg/kg APLME); group 5 (HFD + 300 mg/kg APLME); group 6 (HFD + 450 mg/kg APLME); group 7 (HFD + 600 mg/kg APLME p.o.). High-fat diet was given for 20 weeks after which treatments (APLME and atorvastatin) were given for 4 weeks.Blood was collected, and tissues were harvested for biochemical and histological analyses. Standard chemical methods and gas chromatography-mass spectroscopy profiling were employed to determine the APLME phytoconstituents. Data were analyzed using one way analysis of variance with Tukey’s post-hoc test to separate means at p<0.05.The bioactive phytochemicals mainly found in APLME were benzofuran-2,3-dihydro-Coumaran, phytol-acetate, and 3-o-Methyl-d-glucose. Rats administered HFD only showed significant (p<0.05) increase in MDA levels in serum, liver, heart, and kidney with values of 53.55±0.50,12.70±0.15,10.47±0.35, and 7.941±0.08μmol/g proteinrespectively when compared to the control. The APLME-treated groups showed a dose-dependent significant decrease in all tissues, compared to the HFD group, with the 600 mg/kg APLME group having 17.80±0.77,1.69±0.10,3.36±0.16, and 3.27±0.10 μmol/g protein respectively. Conversely, there were significant (p<0.05) increases in SOD, CAT, GSH, GPx, GST, and G6PDH activities in a dose-dependent manner when compared to the HFD-group. Furthermore, HFD significantly (p<0.05) lowered the anti-inflammatory biomarker IL-10 while significantly (p<0.05) increasing the levels of pro-inflammatory biomarkers TNF-α, MPO, and hs-CRP when compared to the control. Reduction in pro-inflammatory with parallel significant (p<0.05) increase in anti-inflammatory biomarkers resulted from APLME treatment. APLME-treated groups had significant (p<0.05) decrease in lactate dehydrogenase (LDH), creatine kinase isozyme (CK-MB), and aspartate aminotransferase, with the 600 mg/kg APLME group having80.14±1.90, 92.81±1.84, and 125.6±2.01 U/L activities respectively which were significantly (p<0.05) elevated in HFD. Lipid profile of APLME-treated groups resulted in a significant increase in HDL-C and APO A-I, with a corresponding reduction in serum total cholesterol, triglycerides, LDL-C, VLDL-C, phospholipids, NEFA and APO B in the 600 mg/kg APLME-group having 67.77±0.19, 79.56±1.44, 20.75±1.29, 15.91±0.47, 44.99±1.34, 5.96±0.33 and 18.52±0.35 mg/dL respectively. Additionally, APLME at 600 mg/kg significantly (p<0.05) decreased HMG-CoA reductase (34.61±0.77 to 22.64±0.36 U/L), Fatty acid synthase (10.70±0.19 to 3.38±0.29 U/L) but increased Lecithin cholesterol acyltransferase (1.63±0.14 to 10.41±0.19 U/L) activities when compared with HFD-group. The liver of both APLME-treated and HFD-group showed mild to moderate portal sinusoidal congestion and cellular infiltration but no visible lesion in the heart and kidney. Conclusively, oral administration of Abrusprecartorius leaf methanolic extract at 600 mg/kg lowered high fat diet-induced oxidative, inflammatory and dyslipidemic abnormalities in male Wistar rats.