methyl-jasmonate and Disease-Models--Animal

Cancer cells apply the Warburg pathway to meet their increased metabolic demands caused by their rapid growth and proliferation and also creates an acidic environment to promote cancer cell invasion. 3-bromopyruvate (3-BrP) as an anti-cancer agent disrupts glycolytic pathway. Moreover, one of the mechanism of actions of Methyl Jasmonate (MJ) is interference in glycolysis. Hence, the aim of this study was to evaluate MJ and 3-BrP interaction. MTT assay was used to determine IC50 and synergistic concentrations. Combination index was applied to evaluate the drug- drug interaction. Human tumor xenograft breast cancer mice was used to evaluate drug efficacy in vivo. Tumor size was considered as a drug efficacy criterion. In addition to drug efficacy, probable side effects of these drugs including hepatotoxicity, renal failure, immunotoxicity, and losing weight were evaluated. Serum alanine aminotransferase and aspartate aminotransferase for hepatotoxicity, serum urea and creatinine level for the possibility of renal failure and changes in body weight were measured to evaluate drug toxicity. IL10 and TGFβ secretion in supernatant of isolated splenocytes from treated mice were assessed to check immunotoxicity. 3-BrP synergistically augmented the efficacy of MJ in the specific concentrations. This polytherapy was more effective than monotherapy of 3-BrP, MJ, and also surprisingly cyclophosphamide as a routine treatment for breast cancer in the tumor bearing mice. These results have been shown by decrease in tumor volume and increase of tumor growth inhibition percentage. This combination therapy didn't have any noticeable side effects on kidney, liver, and immune system and body weight.

Topics: Acetates; Affinity Labels; Animals; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Cyclopentanes; Disease Models, Animal; Female; Mice; Oxylipins; Plant Growth Regulators; Pyruvates; Xenograft Model Antitumor Assays

Objectives Purinergic signaling pathway has been implicated in maladaptation of animals subjected to chronic stress. Previous studies have shown that methyl jasmonate (MJ) exhibited adaptogenic properties in mice exposed to unpredictable chronic mild stress (UCMS) via antioxidant and neuroprotective-related mechanisms. Methods This study evaluated the role of purinergic system in adaptogenic-like activity of MJ. Male Wistar rats were treated intraperitoneally with vehicle (10 mL/kg) or MJ (25, 50, or 100 mg/kg) 30 min prior exposure to UCMS. Thereafter, rats were assessed for swimming endurance in forced swim test (FST) and post-swimming motor coordination on beam walk test (BWT) apparatus. The rats' brains were processed for adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine deaminase, and arginase quantification. Hematological parameters, cholesterol, triglyceride, creatinine, and urea nitrogen were also determined. Results MJ prolonged swimming endurance time and reversed stress-induced post-swimming motor dysfunction. The altered hematological parameters induced by UCMS in rats were significantly (p<0.05) attenuated by MJ. MJ also reversed UCMS-induced alterations of total cholesterol, triglyceride, creatinine, and urea nitrogen levels. MJ averted UCMS-induced alterations in purinergic system by decreasing ATP and ADP hydrolysis, adenosine deaminase, and arginase activities in rats' brains. Conclusions Overall, these findings further suggest that MJ has adaptogenic-like activity in rats exposed to UCMS, which may be related to modulation of the purinergic signaling pathway.

Topics: Acetates; Animals; Antioxidants; Behavior, Animal; Chronic Disease; Cyclopentanes; Depression; Disease Models, Animal; Injections, Intraperitoneal; Male; Neuroprotective Agents; Oxylipins; Rats; Rats, Wistar; Receptors, Purinergic; Signal Transduction; Stress, Psychological

The present investigation was carried out to evaluate anti-inflammatory and membrane stabilizing properties of methyl jasmonate (MJ) in experimental rat models of acute and chronic inflammation. The effects of MJ on acute inflammation were assessed using carrageenan-induced rat's paw edema model. The granuloma air pouch model was employed to evaluate the effects of MJ on chronic inflammation produced by carrageenan in rats. The number of white blood cells (WBC) in pouch exudates was estimated using light microscopy. The levels of biomarkers of oxidative stress, such as malondialdehyde (MDA), glutathione (GSH) and activity of antioxidant enzymes in the exudates, were determined using spectrophotometry. The membrane stabilizing property of MJ was assessed based on inhibition of hemolysis of rat red blood cells (RBC) exposed to hypotonic medium. Our results indicated that MJ (25-100 mg·kg

Topics: Acetates; Animals; Anti-Inflammatory Agents; Cell Membrane; Cyclopentanes; Disease Models, Animal; Edema; Erythrocytes; Glutathione; Humans; Male; Malondialdehyde; Oxylipins; Plant Extracts; Rats; Rats, Wistar

Methyl jasmonate has recently been found to have anti-cancer activity. Methyl jasmonate detached hexokinase 2 from a voltage dependent anion channel causing a reduction in mitochondrial transmembrane potential that led to the release of cytochrome C and apoptosis inducing factor resulting in intrinsic apoptosis. Blocked adenosine triphosphate synthesis caused by mitochondrial injury hampered oxidative phosphorylation and led to cell necrosis. The results were applied to the in vivo treatment of nude mice with a satisfactory effect. Collectively, our results suggest that methyl jasmonate may be an adjuvant therapy for liver tumors due to its mechanism in cancer cells compared to that in normal cells: The major function is to inhibit glycolysis instead of changing aerobic metabolism.

Topics: Acetates; Animals; Apoptosis; Carcinoma, Hepatocellular; Caspases; Cell Line, Tumor; Cell Proliferation; Cyclopentanes; Disease Models, Animal; Drug Resistance, Neoplasm; Energy Metabolism; Glycolysis; Hexokinase; Humans; Liver Neoplasms; Membrane Potential, Mitochondrial; Mice; Mitochondria; Necrosis; Oxylipins; Plant Growth Regulators; Xenograft Model Antitumor Assays

Psychosis is a chronic neuropsychiatric disorder that affects millions of individuals worldwide and impairs the quality of life and productivity of the patients. The clinical efficacy of antipsychotic drugs has been compromised by adverse effects, relapse, and therapeutic failures, thus necessitating search for alternative agents. Methyl jasmonate (MJ) is a bioactive compound reported to have beneficial effects in various neurological disorders. This study was undertaken to investigate the antipsychotic-like effects of MJ in mice. Male Swiss mice were pretreated intraperitoneally with MJ (25-100 mg/kg) or vehicle (10 mL/kg) 60 min prior to bromocriptine (5 mg/kg) or acute injection of ketamine (10 mg/kg). Thereafter, each mouse was observed for stereotype behaviors for 2 min at 10, 15, 20, 30, and 45 min post-bromocriptine injection. Another set of mice received MJ (25-100 mg/kg) or vehicle (10 mL/kg) 60 min after chronic ketamine injection (20 mg/kg, i.p) once daily for 14 consecutive days. Afterwards, locomotor activity and memory function in this sequence were evaluated using open field and Y-maze tests. The levels of malondialdehyde (MDA) and glutathione (GSH) and activity of catalase and superoxide dismutase (SOD) in the brain were determined. MJ significantly inhibited stereotypy behavior induced by bromocriptine or acute ketamine injection, which suggest antipsychotic-like activity. It also attenuated hyper-locomotion and memory deficits induced by chronic injection of ketamine in mice. The increased oxidative stress as shown by the altered brain levels of MDA, GSH, and activity of antioxidant enzymes induced by chronic injection of ketamine was reduced by MJ. Taken together, these findings suggest that MJ demonstrated antipsychotic-like property via mechanism related to its antioxidant property and interference with dopaminergic neurotransmission.

Topics: Acetates; Animals; Antioxidants; Antipsychotic Agents; Brain; Bromocriptine; Cyclopentanes; Disease Models, Animal; Dopamine; Dose-Response Relationship, Drug; Ketamine; Locomotion; Male; Maze Learning; Memory; Memory Disorders; Mice; Oxidative Stress; Oxylipins; Psychotic Disorders; Stereotyped Behavior; Time Factors

Depression is a recurrent neuropsychiatric disorder that affects millions of individuals worldwide and impact negatively on the patients' social functions and quality of life. Studies have shown that i.p injection of lipopolysaccharide (LPS) induces depressive-like behavior in rodents via induction of oxidative stress and neuroinflammation. Methyl jasmonate (MJ), an isolated compound from jasmine plant has gained reputation in aromatherapy for treatment of depression, nervousness and memory deficits. This study was designed to evaluate the effects of MJ on LPS-induced depressive-like behavior in mice. Mice were given MJ (5-20 mg/kg), imipramine (10 mg/kg) or vehicle (10 mL/kg) intraperitoneally for 7 consecutive days. On day 7, treatment was carried out 30 min prior to i.p injection of LPS (830 μg/kg). Twenty four hours after LPS administration, tail suspension, forced swim and sucrose preference tests were carried out. Thereafter, serum corticosterone levels were determined using ELISA. The levels of malondialdehyde (MDA), glutathione (GSH) and tumor necrosis factor-alpha (TNF-α) were determined in brain tissue homogenates. LPS significantly increased immobility time in the tail suspension and forced swim tests when compared with vehicle (p < 0.05), which indicates depressive-like syndromes. However, the increased immobility time was significantly reduced by MJ (5-20 mg/kg) when compared with LPS-treated group. LPS administration also altered the levels of MDA, GSH, corticosterone and TNF alpha in mice, which was significantly reversed by MJ. These findings suggest that attenuation of LPS-induced depressive-like behavior by MJ may be related to suppression of oxidative stress and release of TNF alpha.

Topics: Acetates; Animals; Antidepressive Agents; Antidepressive Agents, Tricyclic; Behavior, Animal; Brain; Corticosterone; Cyclopentanes; Depression; Disease Models, Animal; Imipramine; Infusions, Parenteral; Jasminum; Lipopolysaccharides; Male; Mice; Oxidative Stress; Oxylipins; Plant Extracts; Tumor Necrosis Factor-alpha

Preclinical Research The effects of methyl jasmonate (MJ; 5, 10, 20 mg/kg, i.p), a natural product widely used for the relief of stress, depression, and exhaustion on unpredictable chronic mild stress (UCMS)-induced depression-like behaviors in mice was assessed and compared to those of imipramine (IMP; 10 mg/kg, i.p). MJ and IMP were given 30 min before exposure to UCMS with the procedure repeated daily for 2 weeks; 24 h after the stress session, the tail suspension test (TST) and sucrose preference test were assessed. MJ decreased immobility time in the TST and reversed impaired intake of sucrose relative to the stressed control suggesting antidepressant-like activity. MJ also reduced UCMS-induced increases in corticosterone and MDA (malondialdehyde) levels and attenuated UCMS-induced decreases in GSH and TNF-α levels and SOD activity. These findings suggest that MJ attenuated UCMS-induced depressive-like behaviors through decreased levels of corticosterone and decreasing oxidative stress and neuroinflammation in mouse brain.Drug Dev Res 78 : 381-389, 2017. © 2017 Wiley Periodicals, Inc.

Topics: Acetates; Animals; Behavior, Animal; Brain; Corticosterone; Cyclopentanes; Disease Models, Animal; Glutathione; Imipramine; Male; Malondialdehyde; Mice; Oxylipins; Stress, Psychological; Superoxide Dismutase; Treatment Outcome; Tumor Necrosis Factor-alpha

This study was undertaken to evaluate the adaptogenic-like activity of methyl jasmonate (MJ) in mice exposed to unpredictable chronic mild stress (UCMS). Male Swiss mice were treated with MJ (25-100mg/kg, i.p.) 30 min before exposure to UCMS daily for 14 days prior to testing for memory and anxiety. Thereafter, the blood glucose and serum corticosterone levels were estimated using glucometer and ELISA. The brain concentrations of malondialdehyde (MDA) and glutathione (GSH) were estimated using spectrophotometer. Brain histology and the population of healthy neurons in the hippocampal regions were also assessed. MJ reversed anxiety and memory impairment produced by UCMS, which suggest adaptogenic-like property. The reduction in the weight of adrenal gland and liver in MJ-treated groups further indicates adaptogenic activity. It further decreases the blood glucose and serum corticosterone levels in UCMS-mice. Also, MJ decreases the concentrations of MDA and elevated the levels of GSH in the brain of mice exposed to UCMS. Brain histology revealed that MJ attenuated UCMS-induced degeneration and death of neuronal cells in the pyramidal layer of the cornu ammonis 3 (CA3) and the sub-granular zone of the dentate gyrus of the hippocampus. Moreover, MJ decreased the population of dead neuronal cells of the pyramidal layer of the CA3 and the sub-granular zone of the dentate gyrus of the UCMS-mice, which suggests neuroprotection. Taken together, these findings suggest that MJ demonstrated adaptogenic-like activity in mice; which might be related to modulation of serum corticosterone levels, inhibition of oxidative stress and neuroprotection.

Topics: Acetates; Adaptation, Ocular; Adrenal Glands; Analysis of Variance; Animals; Anti-Anxiety Agents; Blood Glucose; Body Weight; Brain; Chronic Disease; Corticosterone; Cyclopentanes; Disease Models, Animal; Dose-Response Relationship, Drug; Glutathione; Liver; Male; Malondialdehyde; Maze Learning; Mice; Neurons; Oxylipins; Stress, Psychological

Methyl jasmonate (MJ) is a hormone released by plants in response to external stress, injury or pathogenic invasions. This present investigation evaluated the antidepressant effect of intraperitoneal doses of MJ in mice. Mice were given MJ in the doses of 10, 25 and 50 mg/kg daily for 7 days and then subjected to forced swim test (FST), tail suspension test (TST) and yohimbine lethality test (YLT). The results showed that MJ produced a significant decrease in the period of immobility in the FST and TST, indicating antidepressant activity. MJ potentiated the toxic effect of yohimbine in the YLT, which further suggests antidepressant property and also indicates facilitatory effect on both serotonergic and noradrenergic systems respectively. However, MJ did not significantly alter the spontaneous motor activity of the animals, which indicates a lack of central nervous system stimulant effect. Taken together, these findings suggest that MJ has antidepressant activity and the mechanisms underlying this effect may involve serotonergic and noradrenergic systems.

Topics: Acetates; Animals; Antidepressive Agents; Behavior, Animal; Cyclopentanes; Depression; Disease Models, Animal; Female; Hindlimb Suspension; Immobility Response, Tonic; Male; Mice; Motor Activity; Norepinephrine; Oxylipins; Plant Growth Regulators; Serotonin; Swimming; Yohimbine