EVALUATION OF MECHANISMS UNDERLYING ANTIDEPRESSANT-LIKE EFFECT OF METHYL JASMONATE IN MICE
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Date
2017-11Auteur
UGBOMAH, A.N
Type
ThesisLa langue
enMetadata
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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.
Assujettir
Methyl jasmonateAntidepressant-like activity
Antidepressant-like activity
Monoaminergic antagonist
Neurotransmission
Oxidative stress
Remarques
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