NEURO- AND CARDIO-PROTECTIVE PROPERTIES OF AQUEOUS-METHANOLIC LEAF EXTRACT OF AFRICAN LOCUST BEAN (Parkia biglobosa, (Jacq.) R. Br. ex G. Don

Abstract

The present study was designed to investigate aqueous-methanolic extract of P. biglobosa leaf (PBE) for its constituents, neuroprotective and cardioprotective properties in rats with a view to providing justification for its ethnomedicinal use. PBE was screened for phytochemical constituents and its antioxidant and free radical scavenging properties in vitro. Rat brain hippocampal slices were incubated with PBE (25, 50, 100, 200 μg/ml) to investigate its neuroprotective effects. Equally free phenolics (FPPB) and bound phenolics of PBE (BPPB) were investigated for their effects on enzymes of neurological significance (Na+, K+ ATPase and acetylcholinesterase). The cardioprotective potential of the extract was investigated by evaluating its angiotensin-converting enzyme (ACE) inhibitory and hypotensive effects in normotensive albino rats as well as its ability to protect against doxorubicin-induced cardiotoxicity. Finally, the toxicity of extract on extra cardiac tissues was determined in rats pretreated with PBE (75 mg/kg) over a 30-day period. PBE gave positive results for the presence of saponins, tannins, cardiac glycosides and terpenoids. The total flavonoids and total phenolics concentrations are 121.30 ± 3.2 mg quercetin equivalent/g extract and 55.40±1.2 mg gallic acid equivalent/g extract respectively. The extract showed a trolox equivalent antioxidant concentration (TEAC) value of 0.06 and concentration-dependent inhibition of membrane peroxidation induced by FeSO4 (IC50:75.87 ± 2.1μg/ml and 89.34 ± 2.5μg/ml) and SNP (IC50:28.1±1.6μg/ml and 17.25±0.78μg/ml) in rat liver and brain homogenates respectively. PBE further showed ability to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical (IC50: 98.33±10.0 μg/ml), considerable ferric reduction and moderate fe2+ chelation. HPLC-DAD analyses revealed the presence of catechin, epigalocatechin, rutin, quercetin, gallic, chlorogenic and caffeic acids as bioactive phenolics. Parkia biglobosa phenolics exhibited ACE inhibitory effect (FPPB; 16.22±6.0 μg/ml and BPPB; 47.80±3.1 μg/ml) while only FPPB (5, 10 μg/ml) caused significant increase (P<0.01) in cerebral Na+, K+ ATPase activity. Both PBE and its major polyphenol, catechin mitigated SNP- or CaCl2-dependent mitochondrial generation of ROS and Ca2+-induced swelling but only PBE produced mild depolarization of the ΔΨm. Also, both PBE and catechin decreased basal ROS generation and blunted the pro-oxidant effects of neurotoxicants in hippocampal slices. PBE rescued hippocampal celluar viability from SNP damage and caused a significant boost in hippocampus Na+, K+ Atpase activity. Futhermore, PBE exhibited cardioprotection by preventing doxorubicin-induced dyslipidemia, elevations of cardiac malondialdehyde, serum creatine kinase-MB, lactate dehydrogenase and reduction in the levels/or activities of cardiac antioxidant enzymes and molecules. Additionally, PBE exerted hypotensive effect by reducing the mean arterial blood pressure and heart rate in rats. The safety of PBE at the evaluated dosages was buttressed as the extract did not adversely affect biochemical indices of damage to vital organs. The results suggest that PBE possesses cardioprotective and hypotensive potentials through its antioxidant, anti-hyperlipidemic and ACE inhibitory activities. Equally both the phenolics and non-phenolics compounds in it exhibited neuroprotective potentials.