ABSTRACT
There is a growing consciousness of the universal role of oxidative stress (OS) in neurodegenerative disorders owing to its involvement in neuronal death. Reports indicate that toxins, such as lead and 1- methyl-4-phenylpyridinium (MPP+ ), cause a variety of neurological deficits via OS. However, exogenous antioxidants have been demonstrated to be effective against disorders linked to OS. Accordingly, this study was designed to investigate the in-vitro activities of aqueous Irvingia gabonensis stem bark extract (IGE) and its alkaloid fraction, as well as the in-vivo activity of IGE in models of neurotoxicity. For the in-vivo study, fifty-six (56) adult Wistar rats (n=7) were randomly assigned into groups A (control), B (100 mg/kg body weight [BW] of lead acetate [Pb] only), C (200 mg/kg BW of IGE and Pb), D (400 mg/kg BW of IGE and Pb), E (500 mg/kg BW of vitamin E and Pb), F (200 mg/kg BW of IGE only), G (400 mg/kg BW of IGE only), and H (500 mg/kg BW of Vitamin E only). After twenty-eight days of oral administration, neurobehavioral activities were evaluated and rats were sacrificed to harvest the cerebra, cerebella, and hippocampi for biochemical and histological assessments. For the in-vitro study, the human neuroblastoma SH-SY5Y cells were seeded at a density of 104 /well and treated for twenty-four hours as follows; plates I (control), II (2000 μM of MPP+ ), III (12.5 μg/mL of IGE and 2000 μM MPP+ ), IV, (25 μg/mL of IGE and 2000 μM MPP+ ), and V (50 μg/mL of IGE and 2000 μM MPP+ ), respectively. Also, the SH-SY5Y cells were pre-treated with the alkaloid fraction of I. gabonensis at the same concentration and duration. In-vivo results revealed that Pb-exposed rats demonstrated significant (p<0.05) weight loss, increased anxiety, impaired cognitive and locomotor functions, dysregulated antioxidant enzymes activity, and increased lipid peroxidation. Also, severe histological alterations were observed in the cerebrum, cerebellum, and hippocampus of Pb-exposed rats. However, pretreatment of rats with IGE attenuated the adverse effects induced by Pb. For the MPP+ -exposed SH-SY5Y cells, there was a significant reduction (p<0.05) in cell viability, morphological alterations, depletion of ATP levels and upregulation of caspase 3/7. However, pretreatment with IGE and its alkaloid fractions mitigated the adverse effects induced by MPP+ . Altogether, IGE and its alkaloid fraction exhibited potent neuroprotective activity in both in-vivo and in-vitro experimental models. Consequently, this study demonstrates the potent neuroprotective activity of I. gabonensis and offers translational research implications that I. gabonensis can be further developed into useful clinical formulations against neurological disorders linked to OS.
