Browsing by Author "Saheed O. Afolabi"

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    Effect of intranasal insulin on peripheral glucose profile in dexamethasone-induced insulin resistance in Wistar rats
    (Published by Elsevier, Netherlands, 2018-12) Anoka A. Njan; Chloe O. Fatigun; Abdul-Musawwir Alli-Oluwafuyi; Olufunke E. Olorundare; Saheed O. Afolabi; Olugbenga Akinola; Abdulbasit Amin
    This study evaluates the therapeutic potential of intranasal insulin (INI) in dexamethasone-induced insulin resistance in Wistar rats. In the first phase of the study, thirteen, healthy, untreated male Wistar rats were divided into 2 groups and administered either vehicle (0.9% Normal saline, 20 µl) or insulin (2 IU) intranasally to assess intranasal delivery of insulin in brain. In the second phase of experiments, to evaluate the acute effects of intranasal insulin on peripheral blood glucose, intranasal or intraperitoneal insulin was co-administered with or without dexamethasone 10 mg/kg to 26 male Wistar rats and blood glucose monitored. To evaluate effect of intranasal insulin in peripheral metabolic disease model, insulin or vehicle was administered via intranasal or intraperitoneal (IP) route to control or dexamethasone (Dex)-treated (0.5 mg/kg, IP) female Wistar rats for seven consecutive days. Twenty-four hours after last dose, trunk blood was collected via cardiac puncture. Biochemical assay of glucose, lipid and insulin was performed on serum while enzyme activity – glucokinase and glucose-6-phosphatase (G6Pase) or lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G6PDH) were assayed from liver and brain homogenates respectively. Acute intranasal but not intraperitoneal insulin elevated brain insulin after 30 min. In animals administered single dose of 10 mg/kg dexamethasone, intranasal and intraperitoneal insulin lowered blood glucose within one hour. However, only the former’s effect was maintained at the 3rd and fourth hour. Dex-induced hyperglycemia was associated with increased hepatic glucose-6-phosphatase activity and decreased high-density lipoprotein (HDL), these effect were attenuated by subchronic (INI) administration. Also INI did not induce oxidative stress in the brain which suggests no brain damage during the period of study. Subchronic administration of INI was able to reduce the effect of Dex-induced hyperglycemia that is associated with increased hepatic glucose-6-phosphatase activity and decreased high-density lipoprotein (HDL) without damage to the brain. We demonstrate the potential of brain targeting with intranasal insulin in a rat model of insulin resistance and peripheral metabolic disease.
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    Identification of neurotherapeutic constituents in Ocimum gratissimum with cholinesterase and mono amine oxidase inhibitory activities, using GC-MS analysis, in vitro, and in silico approaches
    (Informatics in Medicine Unlocked, 2023-05-04) Anoka A Njan; Esther O. Olaleye; Saheed O. Afolabi; Immanuel Anoka-Ayembe; Gideon A. Gyebi; Amase Nyamngee; Udoka N. Okeke; Solomon O. Olaoye; Fortune M. Alabi; Oluwapelumi P. Adeleke; Hussaini D. Ibrahim
    Neuroprotective activities of various extracts of Ocimum gratissimum (OG), have been reported, but there is paucity of information on its neurotherapeutic constituents. This study is aimed at identifying the neurotherapeutic constituents in OG leaves using in vitro assays, GC-MS chemical investigation and in silico studies including molecular docking, ensemble-based docking, molecular dynamics (MD) simulation, clustering and ADMET filtering analysis. Methanol extract of O gratissimum (MEOG) and solvent-partition (n-hexane, ethylacetate, and methanol residue fraction) of MEOG were investigated for in vitro acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and monoamine oxidase B (MAO-B) inhibition at concentration of 0.65, 12.5, 2.5, 5, and 10 mg/mL, using donepezil, phenazine methosulfate and selegiline as reference inhibitors for AChE, BChE and MAO B respectively. n-hexane solvent partition fraction was further investigated using GC-MS analysis. Identified compounds were screened against human AChE, BChE and MAO-B activities using molecular docking and molecular dynamics. The lead phytochemicals were further analysed for ADMET in silico analysis. MEOG and the 3 fractions (n-hexane, ethylacetate, and methanol residue fraction) inhibited the activities of AChE, BChE and MAO-B in a concentration-dependent manner with AChE (IC50 = 2.380, 2.022, 2.066 and 1.079 mg/mL respectively), BChE (IC50 = 2.261, 2.126, 2.630 and 1.465 mg/mL respectively) and MAO-B (IC50 = 2.345, 1.584, 2.933 and 2.935 mg/mL respectively). From the 38 GC-MS identified compounds, 7 hit compounds were further subjected to ensemble-docking, the lead phytochemicals (LP): cholestane and 3-methoxy-morphanin presented highest multiple binding tendencies to the three enzymes. Cholestane had the highest binding energies of −9.9, −9.0 and −11 kcal/mol, while 3-methoxy-morphanin presented the second-best binding energies of −9.3, −8.2 and −10.1 kcal/mol respectively. When compared with the binding pattern of reference inhibitors of the enzyme, lead phytochemicals were orientated in the catalytic sites of the enzyme and interacted with important catalytic residues. The LP-enzyme complexes were stable during the MD simulation analysis. Cholestane and 3-methoxy-morphanin presented favorable ADMET properties over several molecular descriptors and filters, with druggable properties and ability to cross the blood-brain barrier. Hence, cholestane and 3-methoxy-morphanin, in part, or in synergy with other hit phytochemicals, may be responsible for the neurotherapeutic activities of MEOG leaves