http://adhlui.com.ui.edu.ng/jspui/handle/123456789/20 Department of pharmacology and Therapeutics Wed, 25 Feb 2026 10:17:34 GMT 2026-02-25T10:17:34Z http://adhlui.com.ui.edu.ng/jspui/handle/123456789/875 Title: EVALUATION OF ANTPSYCHOTIC EFFECTS OF METHYL JASMONATE IN MICE Authors: ANNAFI, O.S Abstract: Psychosis is a chronic neurological disorder that impairs the quality of life of the patients and remains a major health challenge worldwide. Current drugs used to manage psychosis are expensive and only provide symptomatic relief without altering the underlying pathological derangement. Methyl jasmonate (MJ) is a bioactive compound known to have beneficial effects against a wide range of neurological disorders. However, its usefulness in treatment of psychosis has not been scientifically proven. Thus, this study was undertaken to investigate the effects of MJ on psychosis in animal models. Fifty male Swiss mice (23.5±1.5 g) were assigned to 10 groups to evaluate acute antipsychotic-like effect of MJ on bromocriptine or ketamine-induced stereotypy. Groups 1-5 received 1% ethanol (vehicle, 10 mL/kg, i.p.), MJ (25, 50, 100 mg/kg, i.p.) and haloperidol (1 mg/kg, p.o.) 60 minutes prior to bromocriptine (5 mg/kg, p.o.) treatment, while groups 6-10 received vehicle (10 mL/kg, i.p.), MJ (25,50,100 mg/kg, i.p.) and risperidone (0.5 mg/kg, p.o.) 60 minutes prior to ketamine injection. Thereafter, each mouse was placed independently in an observation chamber (20 cm × 20 cm × 23 cm) and stereotyped behaviours were observed for 2 min at 10, 15, 30, 45 and 60 min after bromocriptine or ketamine injection. Another 36 mice (n = 6) were also allotted into treatment groups. Group 1 received vehicle (10 mL/kg, i.p.) while groups 2-6 were treated with ketamine (20 mg/kg, i.p.) once daily, for 14 days. Then, from 8th to 14th day, group 2 was treated with vehicle (10 mL/kg, i.p.) while Group 3-6 received MJ (25,50.100 mg/kg, i.p.) and risperidone (0.5 mg/kg) 60 minutes after ketamine injection. Hyper-locomotion was then measured as an index of psychotic-like behaviour using the open field chamber while memory was assessed using the Y-maze. Thereafter, whole brain samples were used to assay for malondialdehyde, reduced glutathione (GSH), catalase and Superoxide Dismutase (SOD) using spectrophotometric techniques. Histology of prefrontal cortex, hippocampus and substantial nigra were viewed in ketamine-treated mice and neuronal density was determined. Data were analysed using descriptive statistics and ANOVA at α0.05. Methyl jasmonate (25, 50 and 100 mg/kg) significantly reduced stereotypy score (0.62±0.21, 0.24±0.10 and 0.06±0.04) relative to vehicle (1.84±0.15) and (0.50±0.08, 0.36±0.06, 0.26±0.07) relative to vehicle (1.52±0.10) induced by bromocriptine and ketamine, respectively. Methyl jasmonate significantly ameliorated ketamine-induced hyper-locomotion (74.67±4.70, 75.67±2.88, 78.00±4.16 s) compared to vehicle (185.0±3.63) and memory deficit (80.1±2.8, 71.2±2.9, 57.0±3.4 %) relative to vehicle (53.7±2.0%). Methyl jasmonate reduced malondialdehyde concentration (19.96±1.64, 22.84±1.16, 24.65±1.70 μmol/g tissue) relative to vehicle (33.72±2.28 μmol/g tissue) but increased GSH levels (47.43±2.22, 42.23±2.83, 37.26±1.84 μmol/g tissue) compared to vehicle (21.95± 2.69 μmol/g tissue). Methyl jasmonate also increased catalase level in the brain homogenate (86.63±4.65, 83.36±4.24, 76.06±3.22 units/mg protein) relative to vehicle (59.91±3.94 units/mg) and SOD (27.52±1.63, 24.41±1.49, 19.71±1.59 units/mg protein) compared with vehicle (13.08±1.33 units/mg protein), respectively. Brain histology revealed that MJ has protective property on neuronal cells compared to ketamine-treated mice. Methyl jasmonate demonstrated antipsychotic property via activation of antioxidation pathway in Swiss mice. Description: A dissertation submitted to the department of Pharmacology and Therapeutics, Faculty of Basic Medical Sciences, University of Ibadan in partial fulfillment of the requirements for the award of the degree of Master of Philosophy (Pharmacology) of the University of Ibadan, Nigeria. Sun, 01 Jan 2017 00:00:00 GMT http://adhlui.com.ui.edu.ng/jspui/handle/123456789/875 2017-01-01T00:00:00Z http://adhlui.com.ui.edu.ng/jspui/handle/123456789/844 Title: EVALUATION OF ANTIPSYCHOTIC EFFECTS OF METHYL JASMONATE IN MICE Authors: ANNAFI, O.S. Abstract: Psychosis is a chronic neurological disorder that impairs the quality of life of the patients and remains a major health challenge worldwide. Current drugs used to manage psychosis are expensive and only provide symptomatic relief without altering the underlying pathological derangement. Methyl jasmonate (MJ) is a bioactive compound known to have beneficial effects against a wide range of neurological disorders. However, its use in treatment of psychosis has not been scientifically proven. Thus, this study was undertaken to investigate the effects of MJ on psychosis in animal models. Fifty male Swiss mice (23.5±1.5 g) were assigned to 10 groups to evaluate acute antipsychotic- Iike effect of MJ on bromocriptine or ketamine-induced stereotype. Groups 1-5 received 1% ethanol (vehicle, 10 mL/kg, i.p.) MJ (25, 50, 100 mg/kg, i.p.) and haloperidol (1 mg/kg, p.o.) 60 minutes prior to bromocriptine (5 mg/kg, p.o.) treatment, while groups 6-10 received vehicle (10 mL/kg, i.p.),MJ (25, 50,100 mg/kg, i.p,) and risperidone (0.5 mg/kg, p.o) 60 minutes prior to ketamine injection. Thereafter, each mouse was pIaced independently in an observation chamber (20 cm 20 cm x 23 cm) and stereotyped behaviours were observed for 2 min at 10, 15, 30, 45 and 60 min after bromocriptine or ketamine injection. Another 36 mice (n = 6) were also allotted into treatment groups. Group 1 received vehicle (10 mL/kg, i.p.) while groups 2-6 were treated with ketamine (20 mg/kg. i.p.) once daily for 14 days. Then, from 8th to 14th day, group 2 was treated with vehicle (10 mL/kg, i.p.) while Group 3-6 received MJ (25,50,100 mg/kg, i.p.) and risperidone (0.5 mg/kg) 60 minutes after ketamine injection. Hyper-locomotion was then measured as an index of psychotic-like behaviour using the open field chamber while memory was assessed using the Y-maze. Thereafter, whole brain samples were used to assay for malondialdehyde, reduced glutathione (GSH), catalase and Superoxide Dismutase (SOD) using spectrophotometric techniques. Histology of prefrontal cortex, hippocampus and substantial nigra were viewed in ketamine-treated mice and neuronal density was determined. Data were analysed using descriptive statistics and ANOVA at α0.05. Methyl jasmonate (25, 50 and 100 mg/kg) significantly reduced stereotype score (0.62±0.21, 0.24±0.10 and 0.06±0.04) relative to vehicle (1.84±0.15) and (0.50±0.08, 0.26±0.07) relative to vehicle (1.52±0.10) induced by bromocriptine and ketamine, respectively. Methyl jasmonate significantly ameliorated ketamine-induced hyper-locomotion (74.61±4.70, 75.67±2.88, 78.00±4.16 s) compared to vehicle (185.0±3.63) and memory deficit (80.1±2.8, 71.1±2.9, 57.0±3.4 %) relative to vehicle (53.7±2.0%). Methyl jasmonate reduced malondialdehyde concentration (19.96±1.64, 22.84±1.16, 24.65±1.70 umol/g tissue) relative to vehicle (33.71±2.28 umol/g tissue) but increased GSH levels (47.43±2.22, 42.23±2.83, 37.26±1.84 umol/g tissue) compared to vehicle (21.95± 2.69 umol/g tissue). Methyl jasmonate also increased catalase level in the brain homogenate (86.63±4.65, 83.36±4.24, 76.06±3.22 units/mg protein) relative to vehicle (59.91±3.94 units/mg) and SOD (27.52± 1.63, 24.41±1.49, 19.71±1.59 units/mg protein) compared with vehicle (13.08±1.33 units/mg protein) respectively. Brain histology revealed that MJ has protective property on neuronal cells compared to ketamine-treated mice. Methyl jasmonate demonstrated antipsychotic property via activation of antioxidation pathway in Swiss mice. Description: A Dissertation submitted to the Department of Pharmacology and Therapeutics, Faculty of Basic and Medical Sciences in partial fulfillment of the requirements for the Degree of Master of Philosophy of the University of Ibadan, Nigeria. Sun, 01 Jan 2017 00:00:00 GMT http://adhlui.com.ui.edu.ng/jspui/handle/123456789/844 2017-01-01T00:00:00Z http://adhlui.com.ui.edu.ng/jspui/handle/123456789/809 Title: ANTI-STRESS POTENTIALS AND THE MECHANISM OF ACTION OF MORIN HYDRATE IN SWISS MICE Authors: OLONODE, E. T. Abstract: Stress, is an integral component of life that distorts body homeostasis. The available anti-stress drugs are often ineffective in combating its multiple effects. Adaptogens with antioxidant and neuroprotective effects are known to relieve stress. Morin hydrate (MH), a flavonoid from Morus alba with known antioxidant and neuroprotective properties has not been investigated for its anti-stress potential. The study was designed to investigate the anti-stress property of MH and its mechanisms of action in mice. Eighty male Swiss mice (22.0 ± 2.5 g) were used for acute studies: Swimming Endurance Test (SET), Anoxic Tolerance Test (ATT) and Acute Restraint Stress (ARS). The SET and ATT consisted of 5 treatment groups each (n = 5): vehicle (normal saline, 10 mg/mL), MH (5, 10, 20 mg/kg) and adaptogen (ginseng, 25 mg/kg), administered intrapertioneally. Thirty minutes later immobility time was measured in SET and convulsion latency in ATT. In ARS, thirty male mice were allotted into treatment groups I-VI (n = 5): vehicle(10 mg/mL), vehicle-stress control (10 mg/mL), MH (5, 10, 20 mg/kg) and ginseng (25 mg/kg), and treated for 7 days prior to being restrained except group 1. Thereafter, mice were assessed for anxiety and depression in Elevated-Plus Maze (EPM) and Forced-Swim Test (FST), respectively. For chronic studies, ninety male mice were used in 3 models [Chronic- Restraint Stress (CRS), Paradoxical Sleep-deprivation (PSD) and Chronic-Unpredictable Stress (CUS) and grouped, respectively as in ARS. In CRS, mice were pre-treated and restrained for 14 days, and thereafter assessed for anxiety and depression in Mice were sleep-deprived for 48 hours in PSD, and exposed to stressors for 14 days in CUS before testing for memory and anxiety behaviours using Y-maze and EPM, respectively. Brain glutathione (GSH), malondialdehyde, nitric-oxide and blood glucose were determined spectrophotometrically in ARS, CRS, PSD and CUS. Serum corticosterone, brain tumor necrosis factor-alpha (TNF-α) and interleukin-l beta were measured in CUS using ELISA. Brain nuclear factor-kB (NF-kB) and inducible nitric-oxide synthase (iNOS) expressions in CUS were measured using immunohistochemistry. Data were analysed using ANOVA at α0.05. Morin hydrate (5, 10, 20 mg/kg) significantly reduced immobility (10.8 ± 0.20, 7.04 ± 0.77, 9.16± 0.59 s against 11.9 ± 0.25 s) in SET and prolonged convulsion latency ATT (33.1 ± 1.26, 34.1 ±2.40, 34.8 ± 1.06 s against 21.9 ± 1.15 s).The MH decreased anxiety, depression-like symptoms, malondialdehyde and nitric-oxide but increased GSH in ARS and CRS. The MH reversed memory impairment (65.87 ± 3.59, 69.17 ± 6.51, I 62.0± 5.12% against 50.87 ± 2.87%) and anxiety (64.75 ± 5.36, 57.75 ± 2.95, 61.00 ± 1.68 s against 45.0 ± 1.87 s) in PSD. Also, MH increased GSH (104.6 ± 8.50, 97.3 ±6.51, 91.5 ± 7.70 µmol/g tissue against 50.22 ±1.41 µmol/g tissue) but decreased malondialdehyde (7.57± 0.25, 4.50 ± 0.13, 3.16 ± 0.22 µmol/g tissue against 8.60 ± 0.14 µmol/g tissue) and nitric-oxide (163.0 ± 8.67, 121.3 ± 6.67, 124.7± 3.33 µmol/g tissue against 338.0 ± 16.77 µmol/g tissue). The MH increased GSH concentration in CUS and ameliorated CUS-induced increases in glucose, malondialdehyde and nitric oxide Ievels compared to controls. Morin hydrate reduced corticosterone (7.93 ± 0.19, 7.18 ±0.21, 7.46 ± 0.20 ng/mL. against 8.54 ±0.14 ng/mL), TNF-α (49.19 ± 0.55, 47.60± 2.48, 35.22 ± I .77 pg/mL against 92.37± 7.90 pg/mL), and interleukin-I beta (74.45 ± 2.18. 46.45 ± 2.71 43.12 ± 1.55 pg/mL, against 98.72 ± 4.03 pg/mL). Morin hydrate reduced iNOS and NF-kB protein levels in CUS. Morin hydrate exhibited anti-stress potential via mechanisms related to inhibition of hypothalamic-pitutary-adrenal axis hyperactivation, oxidative stress and neuroinflammation. Description: A Thesis in the Department of Pharmacology and Therapeutics, submitted to the Faculty of Basic Medical Sciences in partial fulfillment of the requirement for the Degree of Doctor of Philosophy of the University of Ibadan, Ibadan Wed, 01 Aug 2018 00:00:00 GMT http://adhlui.com.ui.edu.ng/jspui/handle/123456789/809 2018-08-01T00:00:00Z http://adhlui.com.ui.edu.ng/jspui/handle/123456789/808 Title: EVALUATION OF MECHANISMS UNDERLYING ANTIDEPRESSANT-LIKE EFFECT OF METHYL JASMONATE IN MICE Authors: UGBOMAH, A.N Abstract: Depression is a chronic, recurrent and severe disease that affects millions of individuals worldwide and impairs the quality of life of the patients. The clinical efficacy of existing antidepressants has been compromised by adverse effects, low remission and delayed onset of action thus necessitating search for alternative agents. Methyl jasmonate (MJ), isolated from Jasminum grandiflorum has antidepressant activity but the mechanisms of action remains unknown. This study was designed to elucidate the class of antidepressants and mechanisms by which MJ elicit antidepressant effect in mice. One hundred and fifteen male Swiss mice (22±1.5g) were used and treated intraperitoneally. Twenty five mice were assigned to 5 groups (n=5): vehicle (distilled water; 10 mL/kg), MJ (5, 10, 20 mg/kg) and imipramine (10 mg/kg), respectively 30 minutes prior to forced swim test (FST) and tail suspension test (TST). Immobility time served as depressive-like behaviour in both tests. For interaction with monoaminergic blockers, 30 mice were allotted to 6 groups (n=5): prazosin (62.5 µg/kg), yohimbine (1 mg/kg), haloperidol (0.2 mg/kg), sulpiride (50 mg/kg), p-Chloro-phenylalanine (100 mg/kg) and metergoline (4 mg/kg), 15 minutes prior to MJ (20 mg/kg), respectively and were subjected to TST, 30 min after MJ treatment. In lipopolysaccharide (LPS) model, 30 mice were allotted into 6 groups (n=5). Groups 1 and 2 received vehicle (10 mL/kg), while groups 3-6 received MJ (5, 10, 20 mg/kg) and imipramine (10 mg/kg), respectively. A week after, groups 2-6 received a single dose of LPS (0.83 mg/kg; i.p) and depressive-like behaviour was assessed using sucrose preference test. In Chronic Unpredictable Mild Stress (CUMS) model, 30 mice (n=5) were similarly grouped as in LPS model. Groups 2-6 were exposed to stressors for 2 weeks and 24 hours later, TST was used to assess depressive-like symptom. Brain homogenates of LPS-treated and CUMS mice were used to determine malondialdehyde, superoxide dismutase (SOD) and reduced glutathione (GSH) by spectrophotometry, while Tumour Necrosis Factor-alpha (TNF-α) and corticosterone were determined by ELISA. Data were analysed using descriptive statistics and ANOVA at α0.05. Methyl jasmonate (5, 10, 20 mg/kg) significantly reduced immobility time in TST (77.50±5.41, 111.8±1.27, 71.52±8.87 s) and FST (99.93±3.24, 90.75±6.40, 71.28±6.70 s) compared to controls (139.40±7.40; 113.4±3.55 s). Monoaminergic antagonists increased immobility time with MJ in TST. In LPS model, MJ increased sucrose preference (53.75±7.47, 60.52±9.42, 61.60±6.74%) versus control (22.50±3.23%). The MJ decreased corticosterone (1.36±0.17, 0.77±0.24, 0.56±0.08 ng/mL), TNFα (16.96±0.52, 17.70±1.59, 12.52±0.26 pg/mL) and malondialdehyde (30.89±2.47, 68.15±3.95, 40.02±1.38 µmol/g tissue) relative to controls (2.68±0.20 ng/mL; 20.67±1.81 pg/mL; 99.88±1.80 µmol/g tissue). The MJ increased GSH concentration and SOD activity. In CUMS model, MJ decreased immobility time (89.60±3.17, 81.00±4.34, 76.20±2.71 s) in TST compared to control (161.00±5.43 s). It also decreased corticosterone, TNFα and malondialdehyde levels compared to controls in LPS model. The MJ also increased GSH concentration (13.27±0.47, 16.41±0.62, 18.93±0.38 μmol/g tissue) and SOD activity (1.77±0.22, 4.38±0.35, 4.79±0.13 units/mg protein) compared to stressed-controls (6.47±0.64 μmol/g tissue; 0.90±0.03 units/mg protein). Methyl jasmonate exhibited antidepressant-like effect via enhancement of monoaminergic neurotransmission, reduction of brain corticosterone, attenuation of oxidative stress and neuroinflammation. Description: A thesis in the department of Pharmacology and therapeutics, submitted to the faculty of Basic Medical Sciences in partial fulfilment of the requirements for the degree of Doctor of Philosophy of the University of Ibadan Wed, 01 Nov 2017 00:00:00 GMT http://adhlui.com.ui.edu.ng/jspui/handle/123456789/808 2017-11-01T00:00:00Z