MODULATION OF KEY BIOCHEMICAL MARKERS RELEVANT TO STROKE BY ANTIARIS AFRICANA LEAF EXTRACT FOLLOWING CEREBRAL ISCHEMIA/REPERFUSION INJURY

Background: Oxidative stress plays a significant role in stroke pathogenesis. Hence, plants rich in antioxidant phytochemicals have been suggested as effective remedies for prevention and treatment of stroke and other neurological diseases. Antiaris africana Engl. (Moraceae) is traditionally used for the management of brain-related problems but there is paucity of data on its anti-stroke potential. Materials and Methods: Ischemia/reperfusion injury was induced by a 30 min bilateral common carotid artery occlusion/ 2 h reperfusion (BCCAO/R) in the brain of male Wistar rats. A sham-operated group which was not subjected to BCCAO/R and a group subjected to BCCAO/R without treatment with MEA served as controls. The ameliorative effect of 14 days of pretreatment with 50 mg/kg or 100 mg/kg A. africana methanol leaf extract (MEA) on BCCAO/R-mediated alterations to key markers of oxidative stress (malondialdehyde, reduced glutathione, xanthine oxidase, superoxide dismutase, catalase and glutathione peroxidase) and neurochemical disturbances and excitotoxicity (myeloperoxidase, glutamine synthetase, Na+/K+ ATPase, acetylcholinesterase and tyrosine hydroxylase), was evaluated and compared with the effect produced by treatment with 20 mg/kg quercetin as a reference standard. Results: Results show that pretreatment with MEA significantly mitigated or reversed BCCAO/R-induced changes in the level or activity of the evaluated biochemical markers of oxidative stress, neurochemical dysfunction and excitotoxicity compared with the BCCAO/R untreated control group (p < 0.05). The effect produced by 100 mg/kg MEA was similar to that of the reference standard, quercetin. Conclusion: These results revealed the neuroprotective potential of A. africana in stroke and other ischemia-related pathologies. Key words: brain ischemia

Quercetin and catechin assuage redox imbalance and neurochemical dysfunction in rotenone-induced neurotoxicity: A comparative in vivo experiment supported by in silico study

Background: Quercetin and catechin are structurally-related compounds that are capable of preventing or attenuating oxidative damage and mitochondrial dysfunction. Rotenone is a naturally occurring compound that has been used to model neurotoxicity characterized by Parkinson disease-like symptoms. Purpose: This study investigated the comparative property of quercetin and catechin, to ameliorate oxidative damage and neurochemical dysfunction in hippocampal and cortical regions of brain of rats intoxicated with rotenone in vivo, supported by in silico study. Method: Male Wistar rats were subcutaneously administered rotenone for 10 days followed by post-treatment with catechin or quercetin (5, 10 and 20 mg/kg) for 3 days. Markers of oxidative stress and neurochemical dysfunction were biochemically estimated in the hippocampus and cortex of the brain of rats while in silico study was carried out to evaluate the molecular interaction of some neurochemical enzymes with the compounds. Result: Quercetin and catechin ameliorated the reduction in complex 1 and Na+K+ATPase activities while attenuating the elevated lactate dehydrogenase activity in the brain of rotenone-intoxicated rats. Disturbances in acetylcholine, dopamine and glutamate metabolism as well as the evoked oxidative stress in rotenone-intoxicated rats were mitigated by quercetin and catechin. The in silico study revealed the key molecular interaction between the flavonoids and targeted enzymes (tyrosine hydroxylase, monoamine oxidase, glutamine synthetase and Na+K+ATPase) to be by hydrogen bond and hydrophobic interaction. Conclusion: Catechin and quercetin significantly assuaged cortical and hippocampal redox stress and attenuated neurochemical dysfunction caused by rotenone toxicity. Furthermore, this study highlighted that the neuroprotective potentials of the flavonoids is a function of their structural patterns, and quercetin elicited superior activity over catechin due to its structural advantages