Alcohol exacerbates psychosocial stress-induced neuropsychiatric symptoms: Attenuation by geraniol.

Adaptation to psychosocial stress is psychologically distressing, initiating/promoting comorbidity with alcohol use disorders. Emerging evidence moreover showed that ethanol (EtOH) exacerbates social-defeat stress (SDS)-induced behavioral impairments, neurobiological sequelae, and poor therapeutic outcomes. Hence, this study investigated the effects of geraniol, an isoprenoid monoterpenoid alcohol with neuroprotective functions on EtOH escalated SDS-induced behavioral impairments, and neurobiological sequelae in mice. Male mice chronically exposed to SDS for 14 days were repeatedly fed with EtOH (2 g/kg, p. o.) from days 8-14. From days 1-14, SDS-EtOH co-exposed mice were concurrently treated with geraniol (25 and 50 mg/kg) or fluoxetine (10 mg/kg) orally. After SDS-EtOH translational interactions, arrays of behavioral tasks were examined, followed by investigations of oxido-inflammatory, neurochemicals levels, monoamine oxidase-B and acetylcholinesterase activities in the striatum, prefrontal-cortex, and hippocampus. The glial fibrillary acid protein (GFAP) expression was also quantified in the prefrontal-cortex immunohistochemically. Adrenal weights, serum glucose and corticosterone concentrations were measured. EtOH exacerbated SDS-induced low-stress resilience, social impairment characterized by anxiety, depression, and memory deficits were attenuated by geraniol (50 and 100 mg/kg) and fluoxetine. In line with this, geraniol increased the levels of dopamine, serotonin, and glutamic-acid decarboxylase enzyme, accompanied by reduced monoamine oxidase-B and acetylcholinesterase activities in the prefrontal-cortex, hippocampus, and striatum. Geraniol inhibited SDS-EtOH-induced adrenal hypertrophy, corticosterone, TNF-α, IL-6 release, malondialdehyde and nitrite levels, with increased antioxidant activities. Immunohistochemical analyses revealed that geraniol enhanced GFAP immunoreactivity in the prefrontal-cortex relative to SDS-EtOH group. We concluded that geraniol ameliorates SDS-EtOH interaction-induced behavioral changes via normalization of neuroimmune-endocrine and neurochemical dysregulations in mice brains.

Effects of glyphosate-based herbicide on gametes fertilization and four developmental stages in Clarias gariepinus.

Comparative toxicology continues to provide information on how the age of every living organism affects the frequency, severity, and nature of the potentially toxic agent. We investigated the effect of glyphosate-based herbicide (GBH) exposure on gametes and four developmental stages of Clarius gariepinus (C. gariepinus) (African Catfish). Gametes from healthy gravid female and mature male C. gariepinus were exposed to GBH in sublethal concentrations of 0.0 (G1, control), 0.02 (G2), 0.05 (G3), 0.1 (G4), 0.5 (G5), and 1.0 (G6) mg/L for 24 h at the standard conditions of temperature and water quality parameters. The surviving embryos were examined microscopically for malformation rate and edema occurrence post-GBH exposure. In a separate experiment; postfryer, fingerling, posfingerling and juvenile C. gariepinus were exposed to G1, G2, G3, G4, G5 and G6 of GBH concentrations daily consecutively for 28 days. Fish growth performance, behavioural changes, haematology, oxidative stress, and histology were assessed. From our results, GBH showed altered morphology 24 h post-fertilization, decreased body weight, growth parameters, behavioural indices, and survival rate in the various developmental stages. Oxidative stress metabolite, malondialdehyde levels, increases in the postfryer > postfingerlin > fingerling > juvenile C. gariepinus following GBH exposure. Leukopenia and thrombocytosis were observed in the postfingerlings and juvenile fish and decrease in the levels of reduced glutathione and activity of superoxide dismutase compared with the control. Histology showed gross necrosis of the fish gills, liver, brain, and cardiac myocytes in the exposed fish. Hence, our findings provide an insight into C. gariepinus developmental toxicity due to GBH, although continuous measurement of glyphosate levels in the fish and fish environment is essential.

Ameliorating Effect of Morin Hydrate on Chronic Restraint Stress-induced Biochemical Disruption, Neuronal, and Behavioral Dysfunctions in BALB/c Mice.

Introduction: Morin hydrate (MH) is a bioflavonoid component of many fruits and vegetables. Our previous research demonstrated that MH provides neuroprotection in mouse models of acute restraint stress and sleep deprivation by attenuating hippocampal neuronal damage and enhancing memory. Based on these findings, our study investigated the role of MH in chronic stress-induced neuronal and biochemical perturbations in BALB/c mice. Methods: Male BALB/c mice were divided into 6 groups (n=6). Groups 1 and 2 received vehicle (10 mL/kg normal saline), groups 3-5 received MH (5, 10, 20 mg/kg IP), while group 6 received ginseng (25 mg/kg) daily and 30 minutes afterward were restrained in a plastic cylindrical restrainer for 14 days. Results: Immobility time in the forced swim test increased in the MH-treated group, indicating an antidepressant-like effect. Also, a reduction in frequency and duration of open arms exploration was observed in the elevated plus-maze (EPM) test in stressed mice, and administration of MH (5, 10, 20 mg/kg, IP) reversed these effects. An increase in blood levels of glucose, triglycerides, total cholesterol, and brain malondialdehyde and nitrite levels was observed in the stressed groups, which was reversed by MH. Furthermore, MH reversed the stress-induced reduction in HDL cholesterol and glutathione (GSH) levels and attenuated stress-induced alterations in the prefrontal cortex and hippocampus. Conclusion: Our findings suggest that MH attenuated chronic restraint stress-behavioral and biochemical perturbations, probably due to its capability to decrease oxidative stress and brain neuronal damage. Highlights: Chronic stress perturbs physiological and psychological homeostasis;Morin hydrate normalized chronic stress-induced biochemical disruptions;Morin hydrate attenuated structural changes in prefrontal cortex and hippocampus. Plain Language Summary: Stress is a state of being overwhelmed by demands exceeding the personal and social means of coping. Exposure to excessive stress has resulted in disruption of neurochemical and physiological processes, which sometimes manifest as behavioural abnormalities. Therefore to cope with the stressful life style, there is need to develop a therapeutic agent of plant origin. Morin hydrate is a flavonoid with known antioxidant and neuroprotective properties; however, its effect in a stressful condition has not been studies. The study thus evaluated ameliorating effect of Morin hydrate on chronic restraint stress-induced biochemical disruption, neuronal and behavioral dysfunctions in BALB/c mice. To achieve this, mice were exposed to chronic restraint stress protocol for fourteen days. Behavioural changes were examined using various techniques. The vital parameters like antioxidant, glucose and nitrite levels were also taken. Our findings show that Morin hydrate prevented behavioral abnormalities and damage to the brain cells. It also inhibited stress-induced biochemical disturbance.

Aqueous extract of dry powder blend of seeds and leaves of Picralima nitida (Stapf) T. & H. Durand reduce pain and inflammation in animal models.

OBJECTIVES: Blend of seeds and leaves of Picralima nitida herein referred to as West African Durand powder (WDP) was investigated for antinociceptive and anti-inflammatory properties. METHODS: Acute toxic effect of the aqueous extract was evaluated in mice of both sexes. Antinociceptive effect of WDP (100-400 mg/kg) was evaluated in models of acetic acid-induced writhing and thermal nociception on hot plate in mice. Carrageenan-induced paw oedema and air pouch rat models were used to evaluate the anti-inflammatory activity of the extract. RESULTS: WDP (2,000 mg/kg) showed no toxic effect in mice. WDP at 100, 200 and 400 mg/kg inhibited abdominal writhings by 59.9, 66.0 and 79.0%, respectively. There was a significant increase in reaction time on the hot plate tests in mice treated with WDP (400 mg/kg). The paw oedema was reduced by WDP (100, 200 and 400 mg/kg) 5 h post-carrageeenan. Exudate volume was significantly reduced to 39.8 and 44.8% by 200 and 400 mg/kg WDP, respectively. WDP reduced Leucocytes counts (23.3 and 57.1%, respectively) and neutrophil counts (28.1 and 60.0%, as well as reduced nitrites, malondialdehyde levels and increased glutathione concentrations in the air pouch. CONCLUSIONS: These results suggest that aqueous extract of blend of seeds and leaves of P. nitida possesses antinociceptive and anti-inflammatory properties.

Cymbopogon citratus aqueous leaf extract attenuates neurobehavioral and biochemical changes induced by social defeat stress in mice.

Objective: Psychosocial stress has been implicated in the genesis of psychiatric disorders such as memory deficits, depression, anxiety and addiction. Aqueous leaf extract of Cymbopogon citratus (CYC) otherwise known as lemongrass tea has antidepressant, anxiolytic and anti-amnesic effects in rodents. This study was designed to evaluate if C. citratus could reverse the neurobehavioral and biochemical derangements induced by social defeat stress (SDS) in the resident/intruder paradigm. Methods: Intruder male mice were divided into five groups (n = 7): group 1 received saline (10 mL/kg, p.o.; non-stress control), group 2 also received saline (10 mL/kg, p.o.; SDS control) while groups 3-5 had C. citratus (50, 100 and 200 mg/kg, p.o.) daily for 14 d. The SDS was carried out 30 min after each treatment from day 7 to day 14 by exposing each intruder mouse in groups 2-5 to a 10 min confrontation in the home cage of an aggressive resident counterpart. The neurobehavioral features (spontaneous motor activity-SMA, anxiety, memory, social avoidance and depression were then evaluated. The concentrations of nitrite, malondialdehyde and glutathione as well as acetylcholinesterase activity in the brain tissues were also determined. Results: C. citratus (50, 100 and 200 mg/kg) attenuated hypolocomotion, heightened anxiety, depressive-like symptom, memory deficit and social avoidance induced by SDS. The altered levels of oxidative stress and acetyl-cholinesterase in SDS-mice were positively modulated by C. citratus. Conclusion: The results of this study suggest that C. citratus might mitigate psychosocial stress-induced neurologic diseases in susceptible individuals.

Evaluation of the anticonvulsant and anxiolytic-like activities of aqueous leaf extract of Cymbopogon citratus in mice.

Background Anxiety is a common ailment of high co-morbidity with epilepsy, a chronic neurologic disease characterized by recurrent seizures. Current drugs used for these conditions have several limitations such as disabling side effects, relapse, and ineffectiveness in certain population necessitating the search for alternative options. The aqueous leaf extract of Cymbopogon citratus (CYC) is widely used for its various health-promoting effects including relief of seizures and anxiety in ethnomedicine. This present study describes its effects on convulsions, anxiety-like behaviors, and social interaction in mice. Methods Male Swiss mice were pretreated orally with CYC (25, 50, and 100 mg/kg), diazepam (1 mg/kg), or distilled water (10 mL/kg) 60 min before induction of convulsions with intraperitoneal (i.p.) injection of picrotoxin (10 mg/kg), pentylenetetrazole (PTZ; 85 mg/kg), or isoniazid (300 mg/kg). The animals were then observed for the occurrence of seizure for 30 min or 2 h for isoniazid. The effects of CYC on anxiety-like behaviors, social interaction, and spontaneous motor activity (SMA) were evaluated in naive mice. Results CYC (25-100 mg/kg) did not prevent convulsions nor delay the latency to convulsions induced by picrotoxin, PTZ, or isoniazid. Pretreatment with CYC (50 and 100 mg/kg, p.o) produced anxiolytic-like effect, decreased SMA, and also enhanced social interaction behavior in naive mice. Conclusions The results of this study suggest that CYC did not exhibit an anticonvulsant property in mice injected with picrotoxin, PTZ, or isoniazid, but its anxiolytic-like activity and social interaction-promoting effect might be of benefit as an adjuvant in improving the quality of life of epileptic patients.

Antidepressant-like activity of methyl jasmonate involves modulation of monoaminergic pathways in mice.

PURPOSE: The efficacy of current antidepressant drugs has been compromised by adverse effects, low remission and delay onset of action necessitating the search for alternative agents. Methyl jasmonate (MJ), a bioactive compound isolated from Jasminum grandiflorum has been shown to demonstrate antidepressant activity but its mechanism of action remains unknown. Thus, the role of monoaminergic systems in the antidepression-like activity of MJ was investigated in this study. MATERIALS AND METHODS: Mice were given i.p. injection of MJ (5, 10 and 20mg/kg), imipramine (10mg/kg) and vehicle (10mL/kg) 30min before the forced swim test (FST) and tail suspension test (TST) were carried out. The involvement of monoaminergic systems in the anti-depressant-like effect of MJ (20mg/kg) was evaluated using p-chlorophenylalanine (pCPA), metergoline, yohimbine, prazosin, sulpiride and haloperidol in the TST. RESULTS: MJ significantly decrease the duration of immobility in the FST and TST relative to control suggesting antidepressant-like property. However, pretreatment with yohimbine (1mg/kg, i.p., an α2-adrenergic receptor antagonist) or prazosin (62.5µg/kg, i.p., an α1-adrenoceptor antagonist) attenuated the antidepressant-like activity of MJ. Also, pCPA; an inhibitor of serotonin biosynthesis (100mg/kg, i.p) or metergoline (4mg/kg, i.p., 5-HT2 receptor antagonist) reversed the anti-immobility effect of MJ. Sulpiride (50mg/kg, i.p., a D2 receptor antagonist) or haloperidol (0.2mg/kg, i.p., a dopamine receptor antagonist) reversed the anti-immobility effect of MJ. CONCLUSION: The results of this study suggest that serotonergic, noradrenergic and dopaminergic systems may play a role in the antidepressant-like activity of MJ.

Jobelyn® attenuates inflammatory responses and neurobehavioural deficits associated with complete Freund-adjuvant-induced arthritis in mice.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects the physical and psychosocial wellbeing of the patients and a major cause of work disability. Current drugs for its treatment only provide palliative effect, as cure for the disease still remains elusive. Jobelyn® (JB), a potent anti-oxidant and anti-inflammatory dietary supplement obtained from Sorghum bicolor, has been claimed to relieve arthritic pain. Thus, this study was designed to evaluate its effect on inflammatory and biochemical changes as well as neurobehavioural deficits associated with complete Freund-adjuvant (CFA)-induced arthritis in mice. The effect of JB (50, 100 and 200 mg/kg) on inflammatory oedema, neurobehavioural deficits, levels of biomarkers of oxidative stress and inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6) induced by 0.1 mL of CFA (10 mg/mL) was evaluated in male Swiss mice. Oral administration of JB (100 and 200 mg/kg) reduced inflammatory paw volume and reversed sensorimotor deficits induced by CFA. JB also reduced pain episodes, anxiety and depressive-like symptoms in CFA-mice. The increased level of oxidative stress in the joint and brain tissues of CFA-mice was reduced by JB. It also decreased tumor necrosis factor-alpha and interleukin-6 levels induced by CFA in the joint tissue of mice. These findings suggest that Jobelyn® attenuates inflammatory responses induced by CFA in mice via inhibition of oxidative stress and release of inflammatory cytokines. The ability of JB to attenuate CFA-induced nociception, sensorimotor deficits and depressive-like symptom suggests it might improve the quality of life of patients with arthritic conditions.

Effects of Jobelyn® on Isoniazid-Induced Seizures, Biomarkers of Oxidative Stress and Glutamate Decarboxylase Activity in Mice.

INTRODUCTION: Isoniazid-induced seizure, often described as Status Epilepticus (SE), is an emergency condition characterized by repeated convulsive episodes that responds poorly to the currently available anticonvulsant drugs. The current study aimed at ascertaining the effect of Jobelyn® (JB), an African dietary supplement, on seizures, altered oxidative stress, and glutamate decarboxylase activity induced by isoniazid in mice. METHODS: A total of 6 mice received JB (10-50 mg/kg, PO), pyridoxine (300 mg/kg), diazepam (5 mg/kg), or distilled water (10 mL/kg) 30 minutes prior to the induction of SE with injection of isoniazid (300 mg/kg, IP). Thereafter, the mice were observed for the onset of convulsions for a period of two hours. Moreover, the effect of JB on Glutamate Decarboxylase (GAD) activity and biomarkers of oxidative stress (glutathione and malondialdehyde) was also evaluated in the brain homogenates of another set of isoniazid-treated mice. RESULTS: JB (50 mg/kg, PO) prolonged the latency to convulsions, but could not prevent the occurrence of seizure episodes caused by isoniazid. Moreover, JB neither showed any protection against death nor delayed the latency to death caused by isoniazid. However, this dose of JB positively modulated the concentrations of malondialdehyde and glutathione in the brains of mice treated with isoniazid. The activity of GAD, the enzyme responsible for GABA synthesis, increased by JB, which suggested enhanced GABAergic neurotransmission. CONCLUSION: The current study findings suggest that JB prolongs the latency to convulsions, enhances GABAergic neurotransmission, and demonstrates anti-oxidative effect in isoniazid-treated mice.

Methyl Jasmonate Ameliorates Unpredictable Chronic Mild Stress-Induced Behavioral and Biochemical Alterations in Mouse Brain.

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.

Methyl jasmonate attenuated lipopolysaccharide-induced depressive-like behaviour in mice.

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.