http://hdl.handle.net/123456789/58 Mon, 20 Apr 2026 00:59:39 GMT 2026-04-20T00:59:39Z http://hdl.handle.net/123456789/1971 ANTI-PLASMODIAL AND ANTI-INFLAMMATORY ACTIVITIES OF ETHANOL EXTRACT AND ETHYL ACETATE FRACTION OF Psidium guajava Linn LEAVES IN MICE AND RATS AJAO, Mutiu Yombo Inflammation during malaria is a determinant for the progression of plasmodial infection that causes health burdens in humans. Emergence of parasite resistance, absence of dual antiplasmodial and anti-inflammatory properties of current antimalarials necessitates search for new therapeutic strategies. Psidium guajava (Pg) leaves is commonly used in ethno-medicine for the treatment of malaria and other ailments, however, there is dearth of information of its antiinflammatory activity in malaria. This study was therefore designed to investigate the antiplasmodial and anti-inflammatory activities of Pg leaves in mice and rats. Fresh Psidium guajava leaves were authenticated at Forest Herbarium Ibadan (FHI. 110758), airdried, pulverized, extracted with 70% ethanol (EEPg), and partitioned sequentially into n-hexane (PgHXF), dichloromethane (PgDCF), ethyl acetate (PgEAF), and residual aqueous fractions (PgRAF). Ninety male mice infected with Plasmodium berghei (NK65) were used for prophylaxis, 4-Day SuppressiveTest (4-DST) and Curative Test (CT), respectively. For each test, thirty mice were divided into five groups (n=6); 1%Tween80 (control), EEPg (100, 200, 400mg/kg) and chloroquine (10mg/kg). Anti-inflammatory activities of EEPg were investigated in air-pouch model using thirty-six male rats allotted into six treatment groups (n=6); Normal saline (10 mL/kg), lipopolysaccharide (100 ηg/kg), EEPg (100, 200, 400mg/kg) and indomethacin (10 mg/kg). Cytokines (TNF-α, IL-1β) and leucocytes differentials were determined in exudates and blood obtained from the rats. The EEPg fractions were evaluated in mice using 4-DST. The most active fraction PgEAF was evaluated using CT with parasitemia and Mean Survival Time (MST) determined. Blood, liver and spleen were harvested for haematology, liver function (AST and ALT), inflammatory profiles (TNF-α, IL-6, MPO, IFN-γ, and IgG) and markers of oxidative stress (GSH, MDA, SOD, and CAT). Histological analysis of liver and spleen were done using standard method. Data were analysed using ANOVA at α0.05. Chemo-suppression of EEPg in Prophylaxis (84.0, 93.5, 97.2%), 4-DST (32.5, 61.7, 77.3%), CT (59.4, 78.6, 81.0%) was dose-dependent relative to untreated control. Pouch exudates showed significant decrease in levels of TNF-α (30.17±2.53, 37.13±5.0, 28.605±0.59 vs 55.56±1.74pg/mg protein) and IL-1β (193.80±5.67, 158.205±0.94 vs 241.30±4.21pg/mg protein) in EEPg compared with control. The EEPg (400mg/kg) compared with control significantly reduced lymphocytes (35.75±4.87 vs 57.75±1.03) and neutrophils (40.0±3.63 vs 60.25±1.32) counts. The chemo-suppression in 4-DST were PgHXF (49.3%), PgDCF (68.0%), PgEAF (89.1%) and PgRAF (79.5%) relative to untreated control. In CT, PgEAF significantly increased MST (20.83±1.92, 21.5±2.01, 24.83±1.6days) compared with control (10.3±0.1days). The PgEAF (200mg/kg) significantly reduced serum AST (113.6±2.39 vs 123.4±1.07U/L), ALT (92.62±3.05 vs 103.7±2.71U/L) and IFN-γ (73.76±1.94 vs 88.51±0.95pg/mL), and hepatic TNF-α (38.96±1.78 vs 67.15±5.04pg/mg protein) and IL-6 (60.37±2.92 vs 94.89±0.25pg/mg protein), respectively. Packed cell volume (25.67±0.24 vs 20.33±0.24%), haemoglobin (9.77±0.09 vs 6.63±0.09g/dL), platelet (9.33±0.47 vs 4.00±0.00 x103/µL) and serum IgG (18.54±1.01 vs 10.45±1.47pg/mL) increased significantly compared with control. PgEAF significantly reduced hepatic MDA but increased GSH, SOD and CAT, respectively. The PgEAF prevented hepatic and splenic injury in infected mice when compared with untreated control. Ethanol extract of Psidium guajava leaves and its ethyl acetate fraction exhibited anti-plasmodial and anti-inflammatory activities by parasites suppression through immune-modulation and potentiated antioxidant activities. Sat, 01 Jul 2023 00:00:00 GMT http://hdl.handle.net/123456789/1971 2023-07-01T00:00:00Z http://hdl.handle.net/123456789/1969 NEUROBEHAVIOURAL AND BIOCHEMICAL EVIDENCE OF ANTIDEPRESSANT ACTIVITY OF TROXERUTIN IN MICE SOWUNMI, Abimbola Adewale Depression is a debilitating neurological illness characterised by behavioural and neurochemical changes. Conventional antidepressants have poor efficacy, serious side effects and primarily target monoaminergic systems, whereas, there is involvement of neuroinflammation, necessitating newer antidepressants. Troxerutin, a bioflavonoid has been reported to have beneficial antidepressant and anti-inflammatory potentials; however, its mechanism is not fully elucidated. This study was designed to elucidate the antidepressant activity and underlying molecular mechanisms of troxerutin in Swiss mice. Troxerutin antidepressant activity was evaluated in 140 mice. In the acute study, 50 mice were used for Tail Suspension Test (TST) and Forced Swim Test (FST). Animals in each test were assigned into five treatment groups (n=5): distilled water (10 mL/kg), troxerutin (10, 20, 40 mg/kg) and imipramine (25mg/kg), respectively and their duration of immobility was measured 30 minutes after treatment. In the chronic studies, 90 mice were used in three experimental models: Chronic Unpredictable Mild Stress (CUMS), lipopolysaccharide (LPS), and Reserpine-induced Depression (RID). Animals were assigned into six treatment groups (n=5): distilled water (10mL/kg) naive, distilled water (10mL/kg) negative control, troxerutin (10, 20, 40 mg/kg) and imipramine (25mg/kg) respectively. Animals in CUMS, LPS or RID were exposed to stressors for 14 days (CUMS), single dose LPS (0.83mg/kg) after 7 days treatment, and reserpine (0.5mg/kg, daily) for seven days, respectively except for naïve group. The animals were subjected to behavioural assessment: Sucrose Preference Test (SPT), and Y-Maze in CUMS, Novelty Suppressed Feeding (NSF) in LPS, Splash Test in RID. Brain samples were collected for biochemical and histological analysis. In CUMS and LPS, the concentration of BDNF,CREB, MAPKs, corticosterone, TNF-α, IL-6, serotonin, norepinephrine, and dopamine were measured by ELISA and the levels of GSH, malondialdehyde, SOD, and nitrite were measured by spectrophotometry. In RID samples, concentrations of BDNF, CREB, serotonin, norepinephrine, and dopamine were measured. Histology assessment of prefrontal cortex and hippocampus was done by H&E staining for CUMS, and immunohistochemistry staining for iNOS in LPS model. Data were analysed using ANOVA at α0.05. Troxerutin significantly reduced immobility period in TST and FST. In chronic models, troxerutin reversed behavioural deficits compared to negative controls in SPT (75.40±3.38, 74.04±3.10, 75.76±1.62 vs 38.26±5.02%), Y-Maze (76.20±2.28, 75.40±1.03, 77.20±1.42 vs 45.20±1.31%), NSF (101.4±6.99, 100±3.06, 99.6±7.03 vs 216±4.94 sec), and Splash Test (100.6±3.01, 99.20±3.89, 100.6±3.25 vs 32.00±3.01). Troxerutin increased BDNF (184.2±1.47, 185.6±1.42, 190.0±0.50 vs 161.8±2.44pg/mL), MAPKs (2304±117.2, 2279±9.657, 2416±19.94 vs 1778±24.36pg/mL), CREB (15.97±0.60, 16.02±0.58, 17.86±1.35 vs 11.65±0.26ng/mL). Troxerutin also increased serotonin, norepinephrine and dopamine levels, but decreased corticosterone, TNF-α, and IL-6 in CUMS. Similar results were obtained with LPS and RID. Troxerutin compared to negative control increased GSH (0.626±0.02, 0.670±0.03, 0.668±0.03 vs 0.258±0.05µmol/g), SOD (4.90±0.21, 5.08±0.36,5.74±0.31 vs 2.44±0.27U/mg) but reduced nitrite (36.00±4.89, 31.60±4.99, 32.00±5.09 vs 76.00±9.69µg/ml),MDA (3.60±0.74, 3.60±0.24, 3.20±0.20 vs 8.60±0.24nmol/mg) in CUMS, and the same pattern was observed in LPS. Also, troxerutin increased neuronal density in CUMS and decreased iNOS expression in LPS. Troxerutin demonstrated antidepressant-like effect in mice by reversing neurobehavioural deficits in depression via inhibition of neuroinflammatory markers, modulation of oxidative stress, and up-regulation of monoaminergic neurotransmitters, and neurotrophic factors. Sat, 01 Jul 2023 00:00:00 GMT http://hdl.handle.net/123456789/1969 2023-07-01T00:00:00Z http://hdl.handle.net/123456789/1967 EVALUATION OF BENEFICIAL EFFECTS OF LEVETIRACETAM AND CARBAMAZEPINE IN POST STROKE EPILEPSY OGUNJIMI, Luqman Opeoluwa Post-stroke Epilepsy (PSE) has been identified as a significant clinical condition in stroke survivors affecting outcome, quality of life, and hospital cost. They are clinically underestimated without consensus for prophylaxis and treatment. The PSE were empirically managed with older Anti-Epileptic Drugs (AEDs) like Carbamazepine (CBZ), which is not without issues on side effect, drug-drug interactions, and tolerability. Newer AEDs like levetiracetam (LEV) have better safety and tolerability profiles, however there is limited clinical evidence supporting its use in the treatment and prevention of PSE. This study was therefore designed to identify determinants of PSE and compare prophylactic and therapeutic effects of LEV and CBZ monotherapy. The study was divided into three phases and carried out in three purposively selected tertiary health institutions in South West Nigeria. The first phase involved detailed review of records for socio-demographics, aetiology and medication characteristics of 946 adults, aged ≥1 6, and attending epilepsy clinics for a minimum period of 5 years using convenient sampling method. In the second phase, 346 neuroimage confirmed stroke patients who consented were recruited and followed up for 24 months. Post Stroke Outcome (PSO) such as severity, functional outcome, cognition and epileptiform pattern were assessed using National Institute of Health Stroke Scale (NIHSS), Modified Ranking Scale (MRS), Cognitive Screening Instrument for Dementia (CSID), and Electroencephalography (EEG), respectively. Development of PSE, Mortality Rate (MR) and determinants of PSE were evaluated. Those that developed seizures were randomised into AED groups and followed up for 1 2 months and PSO evaluated. The third phase recruited 240 neuroimage confirmed stroke patients with no prior seizure history and randomly divided into Prophylactic Group (PG) [80 each of LEV and CBZ] and Non-Prophylactic Group (NPG). The Lev (250mg) and CBZ (200mg) were administered twice daily and evaluated for PSO. Data were analysed using descriptive statistics, Chi square, and independent student’s t test at α0.05. The records showed that majority of the patients had idiopathic (60.1 %) and structural epilepsy (24.9%), with stroke being the commonest. Two hundred and ninety-four 294(31 .1 %) were not on AED and 51 5(79.0%) of those on AEDs used CBZ. Twenty-seven percent (27%) developed PSE and identified determinants of PSE were severe stroke (p0.01 0), diabetes mellitus (p0.002), cortical involvement (p0.01 6), insomnia (p0.009) and epileptiform pattern (p0.000). Comparing CBZ with LEV groups among PSE, PSO showed higher MR [21 (45.7%) versus 1 1 (23.9%), p0.029], poor outcome on MRS [28(63.6%) versus 1 7(40.5%), p0.032], severe NIHSS [26(56.5%) versus 1 3(28.3%), p0.006] and impaired cognition on CSID [20(43.5%) versus 1 6(34.8%), p0.08], respectively. In phase 3, 1 7(1 0.6%) of PG [1 0(1 2.8%) CBZ versus LEV 7(8.8%)] compared to 1 7(21 .3%) of NPG developed seizures. There was higher MR [22(1 3.7%) versus 34(42.5%), p0.029], poor outcome on MRS [(47(58.8%) versus 59(36.9%), p0.001 )], and CSID score (53.39±26.1 9 versus 36.37±34.06,vii p0.001 ) in NPG compared with PG. Stroke severity, cortical involvement, epileptiform pattern and background diabetes mellitus were identified as predictors of post stroke epilepsy. Levetiracetam exhibited better therapeutic effect than carbamazepine for prophylaxis and treatment of post stroke epilepsy. Sat, 01 Jul 2023 00:00:00 GMT http://hdl.handle.net/123456789/1967 2023-07-01T00:00:00Z http://hdl.handle.net/123456789/1741 NARINGENIN ATTENUATES NEUROBEHAVIOURAL DEFICITS AND BIOCHEMICAL PERTURBATIONS INDUCED BY CHRONIC HYPOXIC STRESS IN MICE OLUGBEMIDE, ABIMBOLA SADIAT Hypoxic stress is known to induce depression, cognitive dysfunction and anxiety-related complications through the activation of oxidative and inflammatory signaling pathways. Thus, inhibition of these pathways might mitigate hypoxic stress-induced neurobehavioural deficits. Experimental studies have shown that naringenin improves neurobehavioural disorders induced by ischemic stroke via inhibition of oxidative stress, neuroinflammation and neurodegeneration. However, there is paucity of information on its protective effects against neurobehavioural deficits induced by Chronic Hypoxic Stress (CHS). Hence, this study was designed to evaluate the effects and biochemical mechanisms of naringenin on CHS-induced depression, memory deficit and anxiety related behaviours in mice. Thirty-five male Swiss-mice (20-22 g) were distributed into 5 groups (n=7) and treated intraperitoneally. Mice in groups I (non-stress control) and 2 (stress-control) received 5%-DMSO (vehicle), while groups 3-5 were treated with 10, 25 and 50 mg/kg analytical grade of naringenin, daily for 14 days. Thirty minutes after daily treatment, each mouse in group 2-5 was subjected to 15 minutes hypoxic-stress in an air-tight 250 mL cylindrical vessel for 14 consecutive days. The neurobehavioural phenotypes (locomotor activity, anxiety, depression and memory) were evaluated on day 15 using standard experimental procedures. Thereafter, the animals were euthanized and the harvested brains were processed for determination of malondialdehyde, reduced glutathione (GSH), nitrite, superoxide-dismutase and catalase using standard biochemical techniques. Serum corticosterone and brain Tumor Necrosis Factor-alpha (TNF-α), and interleukin-1β were assayed using ELISA kits. The expressions of Inducible Nitric Oxide Synthase (iNOS), Nuclear Factor Kappa-B (NF-kB) and Brain Derived Neurotrophic Factor (BDNF) were determined using immunohistochemical techniques. The histomorphological changes of the amygdala were also determined using hematoxylin and eosin, and cresyl violet stains. Data were analysed using descriptive statistics and ANOVA at α0.05. Naringenin (25 and 50 mg/kg) relative to stress-control significantly attenuated CHS-induced locomotor deficit (11.71±0.57 and 12.29±0.57 vs 8.29±0.68) and prolonged immobility time in the test for depression (104.40±9.31 and 139.70±8.34 vs 197.40±6.83sec). It also reduced anxiety like behaviours but did not ameliorate memory deficit induced by CHS. Naringenin (10, 25 and 50 mg/kg) reduced malondialdehyde concentration (36.23±0.96, 40.65±1.60, 67.39±0.32 vs 79.86±4.26 μmol/g tissue) and increased GSH levels (20.85±0.63, 21.99±0.74, 21.65±0.46 vs 17.50±0.50 μmol/g tissue). It also restored the altered brain nitrite content and superoxide dismutase activity but not catalase. Naringenin (25 and 50 mg/kg) reduced CHS-induced increase in the brain contents of TNF-α (37.43±0.63 and 38.84±2.21 vs 50.14±2.26 pg/mL) and interleukin-1β (190.60±11.19, 157.60±6.09 vs 245.70±8.54 pg/mL). The CHS-induced increased brain expressions of iNOSand NF-kBimmunopositive cells were attenuated by naringenin. It also increased BDNF expressions but did not alter serum corticosterone. Histomorphological distortions and loss of neuronal cells in the amygdala induced by CHS was reduced by naringenin. Naringenin attenuated depression and anxiety like behaviours induced by chronic hypoxic stress. The mechanism was via neuroprotection relating to inhibition of oxidative stress, proinflammatory cytokines, expressions of inducible nitric oxide synthase and nuclear factor kappa-B, and upregulation of brain derived neurotrophic factor expressions. Thu, 01 Jul 2021 00:00:00 GMT http://hdl.handle.net/123456789/1741 2021-07-01T00:00:00Z