Ismail Ogunbayode Ishola

Background : Toxicity accounts for nearly one-third of candidate drug attrition, underscoring the need for robust preclinical toxicological evaluation early in the drug development pipeline. To the best of our knowledge, this is the first comprehensive toxicological profiling of Spondias mombin hydroethanolic leaf extract in rodent models in Nigeria. Traditionally used for the treatment of dysentery, gonorrhea, wounds, and anemia, S. mombin hydroethanolic extract warrants systematic evaluation to support its safe therapeutic use and guide the optimization of lead compounds. Methods : Acute toxicity was assessed in mice using a limit test following a single oral dose and a 14-day observation period. Subacute and subchronic toxicity were evaluated in female Wistar rats (n = 6/group and n=10/group) administered 40, 200, or 1000 mg/kg/day of extract for 28 and 60 days, respectively. A control group received distilled water. Hematological and biochemical analyses were conducted post-treatment before humane euthanasia. Results : No mortality or observable signs of toxicity were recorded at doses up to 2000 mg/kg. The extract significantly reduced white blood cell count, absolute lymphocytes, and total bilirubin (WBC: 5.60 × 10³/µL vs. 9.35 × 10³/µL; lymphocytes: 2.08 × 10³/µL vs. 4.28 × 10³/µL; bilirubin: 1.99 µmol/L vs. 2.39 µmol/L). S. mombin extract also exhibited dose-dependent increases in red blood cell and hemoglobin counts, alongside reductions in AST, ALT, and ALP levels in the subacute phase. In the subchronic study, S. mombin significantly reduced total cholesterol (40 mg/kg: 1.96 mmol/L vs. control: 2.85 mmol/L) and bilirubin (1000 mg/kg: 10.69 µmol/L vs. control: 22.58 µmol/L). Conclusion : The validated safety profile of S. mombin hydroethanolic leaf extract supports its continued ethnomedicinal use and highlights its promise as a candidate for further pharmacological development—particularly as a potential hematinic, anti-infective, and hepatoprotective agent.

Parkinson’s disease (PD) is a neurodegenerative disease characterized by Lewy body formation mainly phosphorylated and aggregated α-synuclein, with subsequent neurotoxicity and death of dopaminergic neurons in the basal ganglia. The neuroprotective action of curcumin and piperine has been reported. We used the GAL4/UAS bipartite system for targeted expression of α-synuclein pan-neuronal and dopamine neurons to create genetically induced PD. Hence, in this study we assessed the ameliorative effect of curcumin and piperine on α-synuclein-induced dopaminergic neuron degeneration and photoreceptor degeneration in the Drosophila melanogaster model of PD. Male Drosophila melanogaster (upstream activating sequence (UAS) linked to synuclein (SNCA) flies were crossed with virgin wild-type Can-ton-S, DDC-GAL4 or GMR-GAL4 female flies) cultured on either medium containing graded concentrations of curcumin and/or piperine (5, 10, and 50 μM) or vehicle. The parameters measured included fecundity, larval motility, negative geotaxis, and lifespan. Vehicle, curcumin, or piperine supplementation in SNCA>Cs, SNCA>DDC, or SNCA>GMR flies did not affect fecundity or larval motility, but piperine (5 μM and 10 μM but not 50 μM) supplementation reduced fecundity. SNCA>DDC flies significantly reduced climbing performance and lifespan, peaked in week 4, ameliorated by the curcumin and piperine combination. Moreover, the increased aggregation of synuclein, as evidenced in ommatidial degeneration in SNCA>GMR flies’ eyes, was attenuated by the curcumin and piperine combination. Findings from the present study further reinforced the potential benefit of curcumin and piperine in the management of PD.

Introduction: Globally, the incidence of inflammation and inflammatory disorders has continued to rise at an alarming rate. Entandrophragma utile is a species of flowering plant widely distributed in Africa and has been used for the management of sickle cell disease, rheumatism, ocular inflammation, duodenal and stomach ulcers. This research aims to formulate and evaluate an anti-inflammatory herbal emulgel using an extract from Entandrophragma utile stem bark (EUB). Method: Using a carrageenan-induced paw oedema model, the anti-inflammatory efficacy of EUB the extract was assessed. The formulated Entandrophragma utile emulgels (EUE) were characterized, and their anti-inflammatory activity was demonstrated, by utilizing diclofenac emulgel-treated rats with complete Freund’s adjuvant (CFA)-induced arthritis model as the positive control group. Results: The emulgels formulated had characterization results within acceptable ranges; pH (4.25–5.80), viscosity (418.9–112.8 mPas), spreadability (25.00–31.82 gcm/s), extrudability (30.86–51.02 g/cm²), and a swelling index of (30–60%). The emulgel produced a concentration-dependent inflammatory inhibition with a peak effect (117.97%) at the end of the 4th week which was comparable to that of commercial diclofenac (127.19%). The phytochemical analysis led to the identification of saponins, flavonoids, phenols, and tannins as active secondary metabolites. Conclusions: The stem bark extract of E. utile possessed noteworthy (p < 0.05) reduction in inflammation in comparison to diclofenac and its emulgel formulation showed enormous potential for treating inflammation and pain.

Decline in cholinergic function and oxidative/nitrosative stress play a central role in Alzheimer’s disease (AD). Previous quantitative HPLC profiling analysis has revealed the presence of Pinostrobin, formononetin, vitexin and other neuroprotective flavonoids in Cajanus cajan seed extract. This study was designed to investigate the protective action of Cajanus cajan ethanol seed extract (CC) on learning and memory functions using scopolamine mouse model of amnesia. Materials and methods: Adult mice were pretreated with CC (50, 100, or 200mg/kg, p.o) or vehicle (10ml/kg, p.o) for 16 days consecutively. Scopolamine, a competitive muscarinic cholinergic receptor antagonist (1mg/kg, i.p.) was given an hour after CC pretreatment from days 3 to 16. The mice were subjected to behavioural tests from day 11 (open field test (OFT)/ Y-maze test (YMT) and Morris water maze task (MWM) from days 12-16. Animals were euthanized 1h after behavioral test on day 16 and discrete brain regions isolated for markers of oxidative stress and cholinergic signaling. Molecular docking analysis was undertaken to predict the possible mechanism(s) of CC-induced anti-amnesic action. pre-administration of CC significantly reversed working memory and learning deficits caused by scopolamine in YMT and MWM tests, respectively. Moreover, CC prevented scopolamine-induced oxidative and nitrosative stress radicals in the hippocampus evidenced in significant increase in glutathione (GSH) level, superoxide dismutase (SOD) and catalase (CAT) activities with a marked decrease in malondialdehyde (MDA) production, as well as significant inhibition of hippocampal scopolamine-induced increase in acetylcholinesterase activity by CC. The molecular docking analysis showed that out of the 19 compounds, the following had the highest binding affinity; Pinostrobin (-8.7 Kcal/mol), friedeline (-7.5kCal/mol), and lupeol (-8.2 Kcal/mol), respectively, to neuronal muscarinic M1 acetylcholine receptor, α7 nicotinic acetylcholine receptor and amyloid beta peptide binding pockets, which further supports the ability of CC to enhance neuronal cholinergic signaling and possible inhibition of amyloid beta aggregation. This study showed that Cajanus cajan seeds extract improved working memory and learning through enhancement of cholinergic signaling, antioxidant capacity and reduction in amyloidogenesis.

Decline in cholinergic function and oxidative/nitrosative stress play a central role in Alzheimer’s disease (AD). Our quantitative preliminary study revealed the presence of several neuroprotective flavonoids in Cajanus cajan seed extract. Hence, this study was designed to investigate the protective action of Cajanus cajan ethanol seed extract (CC) on learning and memory functions using scopolamine mouse model of amnesia. Adult mice were first pretreated with CC (50, 100, or 200mg/kg, p.o) or vehicle (10ml/kg, p.o) for 16 days. Scopolamine an anti-muscarinic agent (1mg/kg) was given an hour after CC pretreatment from days 3 to 16. The mice were subjected to behavioural tests (open field test (OFT), Y-maze test (YMT) or Morris water maze task (MWM). Animals were euthanized on day 16 and biochemical analysis was carried on the brain tissue to assay for biomarkers of oxidative stress and cholinergic system. Molecular docking analysis was also done to investigate the possible mechanism(s) through which CC exerts its anti-amnesic action. The results showed that the pre-administration of CC ameliorated working memory and learning deficits caused by scopolamine in YMT and MWM tests, respectively. CC improved cholinergic function via attenuation of scopolamine-induced increase in acetylcholinesterase activity in the hippocampus. Furthermore, CC attenuated scopolamine-induced oxidative stress and increased nitrite generation in the hippocampus evidenced in significant increase in glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) activities with a marked decrease in malondialdehyde (MDA) levels. Phytochemicals obtained from CC displayed significant interaction at the M1 muscarinic acetylcholine receptor, alpha-7 nicotinic acetylcholine receptor and amyloid beta peptide binding pockets which suggests the involvement of these target proteins in the activity of CC. Findings obtained from this study showed that CC improved working memory and learning through enhancement of cholinergic systems and reduction in amyloidogenesis.

It is well established that there is a link between type 2 diabetes mellitus and Parkinson’s disease (PD) evidenced in faster progression and more severe phenotype in patients living with diabetes suggestive of shared cellular pathways; hence, antidiabetic drugs could be a possible treatment options for disease modification. This study evaluated the effect of glimepiride (GMP), a third generation sulphonylurea, on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD in mice. Sixty mice were divided randomly into six individual groups of 10 mice each and dose orally as follows: group 1: vehicle (10 ml/kg, p.o.); group 2: MPTP (20 mg/kg, i.p. × 4 at 2-h interval); groups 3–5: GMP (1, 2, or 4 mg/kg, p.o.) + MPTP (20 mg/kg, i.p. × 4 at 2-h interval); and group 6: GMP (4 mg/kg, p.o.). Effect of glimepiride on motor activities were appraised with the use of open-field test and rotarod performance while non-motor activity was evaluated using force swim test (FST; depression) and Y-maze test (working memory). MPTP induced significant decrease in latency to fall on rotarod, distance covered/rearing in open field, mean speed and climbing in FST, and percentage alternation behavior in Y-maze suggestive of motor and non-motor dysfunction. However, MPTP-induced motor and non-motor dysfunction were ameliorated with glimepiride post-treatment. In addition, MPTP-induced increase in oxidative stress parameters and cholinergic neurotransmission was attenuated by glimepiride. In addition, MPTP-induced nigral dopamine neuron loss (decrease in tyrosine hydroxylase-positive neuron (TH)) and neuroinflammation (activation of glial fibrillary acid protein (GFAP) and ionized calcium binding adaptor molecule 1 (iba-1)) were ameliorated by GMP administration. This study showed that glimepiride ameliorates MPTP-induced PD motor and non-motor deficits through enhancement of antioxidant defense signaling and attenuation of neuroinflammatory markers. Thus, this could be useful as a disease-modifying therapy in the management of PD.