Anthony T. Eduviere

Methyl jasmonate enhances memory performance through inhibition of oxidative stress and acetylcholinesterase activity in mice.

AIMS Current research effort focuses on the development of safer natural compounds with multipronged mechanisms of action that could be used to ameliorate memory deficits in patients with Alzheimers disease, as cure for the disease still remains elusive. In this study, we evaluated the effect of methyl jasmonate (MJ), a naturally occurring bioactive compound on memory, acetylcholinesterase activity and biomarkers of oxidative stress in mice. MAIN METHODS Male Swiss mice were treated with intraperitoneal injection of MJ (10-40 mg/kg) alone or in combination with scopolamine (3mg/kg) once daily for 7 days. Thirty minutes after the last treatment, memory functions were assessed using Y-maze and object recognition tests. Thereafter, acetylcholinesterase activity and levels of biomarkers of oxidative stress were assessed in mice brains using standard biochemical procedures. KEY FINDINGS MJ significantly enhanced memory performance and reversed scopolamine-induced cognitive impairment in mice. MJ demonstrated significant inhibition of acetylcholinesterase activity suggesting increased cholinergic neurotransmission. It further decreased malondialdehyde concentrations in mouse brain indicating antioxidant activity. Moreover, MJ significantly increased glutathione levels and activity of antioxidant enzymes (catalase and superoxide dismutase) in mice brains. The increased oxidative stress; evidenced by elevated levels of malondialdehyde and decreased antioxidant defense systems in scopolamine-treated mice was attenuated by MJ. SIGNIFICANCE The results of this study suggest that MJ may be useful in conditions associated with memory dysfunctions or age-related cognitive decline. The positive effect of MJ on memory may be related to inhibition of oxidative stress and enhancement of cholinergic neurotransmission through inhibition of acetylcholinesterase activity.

Anti-aggressive activity of methyl jasmonate and the probable mechanism of its action in mice.

This study examines the anti-aggressive activity of methyl jasmonate (MJ) and its probable mechanism of action in mice. Male mice that showed aggression after housing individually with female counterparts for 3 weeks or kept in isolation for 4 weeks were treated with MJ, vehicle or haloperidol (HP) 60 min before the test for aggression. Effects of p-chlorophenylalanine (PCPA) or fluoxetine (FL) given alone or in combination with MJ were also investigated. In the interaction studies, PCPA or FL was given to the animals 30 min after MJ injection and aggression testing was carried out 30 min later. Parameters assessed in the study were latency to attack, frequency of attacks, aggressive postures, lateral threats, tail rattling and pursuit frequency. MJ (1, 5, 10 mg/kg) produced a significant dose-dependent decrease in offensive aggressive behaviors. MJ did not impair the defensive mechanisms of the animals and its anti-aggressive effect was not accompanied by sedation or catalepsy. PCPA (50 mg/kg), an inhibitor of 5-hydroxytryptamine (5-HT) biosynthesis, produced a significant increase in aggressive responses and reversed the anti-aggressive effect of MJ. Additionally, FL (10 mg/kg), a 5-HT reuptake inhibitor, produced a significant suppression of aggressive behaviors and also enhanced the antiaggressive effect of MJ. Taken together, these findings suggest that methyl jasmonate exhibits specific anti-offensive aggressive activity and may be relevant in the treatment of reactive aggression in humans. Although, it appears that MJ may be affecting 5-HT(1B) receptors, additional data are needed to clearly define the mechanism(s) by which MJ exhibit antiaggressive activity.

Free radical scavenging effect of donepezil as the possible contribution to its memory enhancing activity in mice.

Donepezil (DP) is the major drug currently used for enhancing memory function in patients with Alzheimers disease (AD), an action ascribed to the elevation of central cholinergic neurotransmission. However, there are indications that DP may protect neurons against injury through the prevention of free radical-mediated neuroinflammation that has been implicated in the pathology of AD. Thus, this study was carried out to examine the effect of DP on memory impairment and on biomarkers of oxidative stress induced by scopolamine (SC) and lipopolysaccharide (LP) in mice.Mice were treated with DP (0.5-4 mg/kg, i. p.) 30 min prior to i. p. injection of SC or LP once daily for 7 days before assessing for memory function utilizing the Y-maze paradigm and levels of biomarkers of oxidative stress using standard biochemical procedures.DP (0.5-2 mg/kg) significantly reversed the memory impairment produced by SC (1 mg/kg) or LP (250 µg/kg) in mice, indicating memory enhancing effect. The increased brain levels of malondialdehyde (MDA) evoked by SC (1 mg/kg) or LP (250 µg/kg), was significantly inhibited by DP (0.5-4 mg/kg), suggesting antioxidant property. Further, DP (0.5-4 mg/kg) significantly inhibited glutathione (GSH) depletion caused by SC (1 mg/kg) or LP (250 µg/kg) in mice brains, which suggest free radical scavenging property.These findings suggest that DP has antioxidant effect, which might be playing a significant role in its memory enhancing activity in mice. However, more detailed studies are necessary to confirm the relevance of this finding and its implications in clinical settings.

Jobelyn® exhibited anti-inflammatory, antioxidant, and membrane-stabilizing activities in experimental models.

Abstract Background: Jobelyn® (JB) is an African sorghum-based food supplement claimed to be efficacious for the treatment of rheumatoid arthritis (RA). Although in vitro studies confirmed its anti-inflammatory property, no study had shown the effect of JB using in vivo animal models of inflammation. Thus, its effects on acute and chronic inflammation in rats were evaluated in this study. Its effect on rat red blood cell (RBC) lysis was also assessed. Methods: Acute inflammation was induced with intraplanter injection of carrageenan and increase in rat paw volume was measured using plethysmometer. The volume of fluid exudates, number of leukocytes, concentrations of malondialdehyde (MDA), and glutathione (GSH) in the fluid were measured on day 5 after induction of chronic inflammation with carrageenan in the granuloma air pouch model. RBC lysis induced by hypotonic medium as determined by release of hemoglobin was measured spectrophotometerically. Results: JB (50–200 mg/kg) given orally produced a significant inhibition of acute inflammation induced by carrageenan in rats. It reduced the volume and number of leukocytes in inflammatory fluid in the granuloma air pouch model of chronic inflammation. It further decreased the levels of MDA in the fluid suggesting antioxidant property. JB elevated the concentrations of GSH in inflammatory exudates indicating free radical scavenging activity. It also significantly inhibited RBC lysis caused by hypotonic medium, suggesting membrane-stabilizing property. Conclusions: JB has in vivo anti-inflammatory activity, which may be related to its antioxidant and membrane-stabilizing properties, supporting its use for the treatment of arthritic disorder.

Morin hydrate mitigates rapid eye movement sleep deprivation-induced neurobehavioural impairments and loss of viable neurons in the hippocampus of mice

Rapid eye movement sleep deprivation distorts the bodys homeostasis and results in oxidative breakdown which may be responsible for a variety of neurological disorders. Some naturally occurring compounds of plant origin with antioxidant and neuroprotective properties are known to attenuate the detrimental effects of REM sleep deprivation. Morin hydrate, a flavonoid from Mulberry has demonstrated antioxidant and neuroprotective activities but its effect in sleep disturbed mice is unknown. The study was designed to explore the neuroprotective effect of Morin hydrate on 48 h. REM sleep deprivation-induced behavioural impairments and neuronal damage in mice. Mice were allotted into six treatment groups (n = 6): groups 1 and 2 received vehicle (10 ml/kg normal saline), groups 3-5 received Morin hydrate (5, 10, 20 mg/kg i.p) while group 6 received ginseng (25 mg/kg) which served as the reference drug. Treatment was performed daily for 5 days and animals were sleep-deprived on the last 48 h. Various behavioural tests (Elevated plus maze, Y-maze, locomotor activity) followed by oxidative parameters (malondialdehyde, nitric oxide, reduced glutathione) and histolopathological changes in the Cornu ammonis 1 (CA1) region of the hippocampus were assessed. Data were analysed using ANOVA at α0.05. Morin hydrate (5, 10, 20 mg/kg) significantly enhanced memory performance, improves anxiolytic-like behaviour, reverses hyperlocomotion, restored depleted reduced glutathione, attenuated raised malondialdehyde and nitric oxide levels as compared to control animals and protects against loss of hippocampal neurons. Results of this present study suggest that Morin hydrate possess neuroprotective effects against sleep deprivation-induced behavioural impairments, oxidative stress and neuronal damage.

Neurobehavioural and Analgesic Properties of Ethanol Bark Extract of Terminalia ivorensis A Chev. (Combrataceae) in Mice.

BACKGROUND Terminalia ivorensis A. Chev (Combretaceae) is a medicinal plant used in folk medicine in the management of pain, rheumatic condition, gastroenteritis and as a tranquilizer in psychotic disorder. OBJECTIVE We evaluated neurobehavioural and analgesic properties of the ethanol bark extract of T. ivorensis (EBETI). MATERIALS AND METHODS Effects of EBETI (1.25, 2.5, and 5 mg/kg) on novelty-induced behaviours were determined using open field test. Anxiolytic effect of EBETI (1.25, 2.5, and 5 mg/kg) was assessed using hole-board and elevated-plus maze paradigms. Analgesic property of EBETI (2.5, 5, and 10 mg/kg) was evaluated using acetic acid induced writhing, formalin and tail immersion tests. The extract was administered once intraperitoneally. RESULTS The LD50 of EBETI was 173 mg/kg. EBETI (1.25, 2.5, and 5 mg/kg) significantly reduced rearing (142.3±1.6, 83.5±1.9, 39.3±1.5) and grooming (33.8±3.4, 28.4±3.0, 18.2±1.7) as compared with controls (180.5±4.9; 52.4±5.2). Treatment with EBETI (1.25, 2.5, and 5 mg/kg) significantly reduced head-dipping on hole-board (9.4±2.3, 6.2±1.9, 5.4±2.9) as compared with control (26.8±1.9). However, there was no anxiolytic effect on EPM. EBETI (2.5, 5, and 10 mg/kg) significantly inhibited abdominal constriction in writhing assay (21.8.0±2.4, 12.2±1.6, 5.8±2.1) as compared with control (35.0±1.7). Inhibition of neurogenic and inflammatory phases of formalin test was notice. However, the extract could not alter response to thermal stimulus in tail immersion test. DISCUSSION AND CONCLUSION EBETI is sedative and has analgesic effect, thus supporting its folkloric use in pain management and as a tranquilizer in psychosis.

Antidepressant-like property of Jobelyn®, an African unique herbal formulation, in mice.

OBJECTIVES The purpose of this investigation was to evaluate whether Jobelyn® (JB) possesses anti-depressant-like property in the mouse forced swimming test (FST), tail suspension test (TST) and yohimbine-induced lethality test (YLT) in aggregated mice. METHODS Mice were given JB (10-100 mg/kg, p.o.) daily for 7 days and then subjected to FST, TST, YLT and open field test. The parameters assessed in both FST and TST were the time (s) spent in active movement (struggling time), first occurrence of immobility (s) and the duration of immobility (s). In the YLT, the mortality rate was recorded 24 h after yohimbine (35 mg/kg, i.p.) administration. In the open field test, the number of line crosses and total distance travelled (m) were measured for 10 min in the open field chamber. RESULTS JB significantly (p<0.05) decrease the duration of immobility both in the FST and TST, which suggests antidepressant-like property. JB significantly (p<0.05) prolonged the time spent in active swimming and delayed the first occurrence of immobility, indicating endurance promoting effect. It potentiated the toxic effect of yohimbine, which further suggests antidepressant-like activity and facilitation of both serotonergic and noradrenergic neurotransmissions. However, JB did not significantly increase the locomotor activity in the open-field test. CONCLUSIONS Jobelyn® has antidepressant-like activity, which may be related to the stimulation of serotonergic and noradrenergic pathways. The ability of Jobelyn® to delay the onset of immobility and to prolong the struggling time support its use as energizer in general body weakness or exhaustion.

Evaluation of the anticonvulsant and anxiolytic potentials of methyl jasmonate in mice.

Abstract Methyl jasmonate (MJ) is one of the most well-studied plant stress hormones belonging to the jasmonate family. Previous studies have shown that MJ potentiated pentobarbitone sleeping time and enhanced GABA-mediated inhibitory neurotransmission, suggesting potential benefits in disorders associated with hyperactivity of the brain. This study was carried out to evaluate whether MJ has anticonvulsant and anxiolytic properties in mice. The anticonvulsant effect was assessed based on the prevention of tonic-clonic seizures induced by chemoconvulsant agents in mice. The anxiolytic property was evaluated utilizing the elevated plus maze (EPM) and light/dark transition paradigms. The effect of MJ on spontaneous locomotor activity (SMA) was also assessed. Mice received intraperitoneal (i.p.) injections of MJ 30 min before the tests were carried out and diazepam (2 mg/kg, i.p.) was used as the reference drug. MJ (50–400 mg/kg) did not protect the mice against tonic-clonic convulsions induced by picrotoxin (10 mg/kg, i.p.) or strychnine (3 mg/kg, i.p.). However, MJ (100, 200, and 400 mg/kg) offered 20, 60, and 100% protection against pentylenetetrazole (100 mg/kg, i.p.)-induced convulsions. In a similar manner to diazepam (2 mg/kg), MJ (400 mg/kg) produced a marked sedative effect as shown by decreases in the number of lines crossed and the duration of ambulation in the open field test. In contrast to diazepam (2 mg/kg), MJ (5–50 mg/kg) did not show anxiolytic effects in the EPM and light/dark transition paradigms. These findings suggest that methyl jasmonate at high doses possessed anticonvulsant properties in the pentylenetetrazole animal model of epilepsy, but did not produce anxiolytic activity in mice.

Flavonoid-Rich Fraction of Ocimum gratissimum Attenuates Lipopolysaccharide-Induced Sickness Behavior, Inflammatory and Oxidative Stress in Mice

PURPOSE Ocimum gratissimum L. leaves has been traditionally used for management of febrile illnesses and symptoms typified of sickness behavior. In this work we investigated the modulatory effect of flavonoid-rich fraction of O. gratissimum leaves (EAFOg) on sickness behavior, inflammatory and oxidative stress responses in LPS-challenged mice. METHOD O. gratissimum leaf was first extracted with n-hexane, chloroform and methanol, and EAFOg was obtained by ethylacetate partitioning of a sequentially resultant methanol extract. The effect of EAFOg (25-100 mg/kg) on acute LPS-induced neurobehavioral impairment in an open field test (OFT) and depressive-like behavior in forced swimming test (FST) was investigated. Serum nitrite and TNF-α, as well as myeloperoxidase (MPO), malondialdehyde (MDA), and reduced glutathione (GSH) levels were determined in liver and brain tissues. RESULT EAFOg prevented the reduction in locomotor and rearing activity in OFT and the increase in immobility time in FST. The fraction significantly attenuated the elevation of serum TNF- α and nitrite levels. EAFOg reversed LPS-induced increase in MDA, MPO, and nitrite levels and attenuated GSH depletion in liver and brain tissues of mice. CONCLUSION Flavonoid-rich fraction of O. gratissimum leaf demonstrated significant modulation of LPS-induced sickness behavior, inflammatory and oxidative stress response in mice. This suggests an important therapeutic strategy in slowing down LPS-mediated hepatic and neuronal disease processes.

Pharmacological evaluation of the analgesic and anxiolytic activities of Jobelyn® in mice.

Abstract Background: This study presents the results of the pharmacological evaluation of the analgesic and anxiolytic potentials of Jobelyn®, a potent antioxidant African herbal formulation, in mice. The analgesic effect was assessed utilizing acetic acid-induced writhing, tail immersion and formalin-induced paw licking pain models. The anxiolytic activity was evaluated using elevated-plus maze (EPM) and light/dark box. Methods: Mice (5/group) were treated with JB (10–200 mg/kg, p.o.) 1 h before the tests were carried out. In the writhing test, the number of abdominal constrictions was recorded for a period of 30 min after induction of nociception with 0.6% acetic acid, i.p. In the tail immersion test, the latency to tail withdrawal responses to noxious heat was measured. The duration of paw licking (s) was measured as an index of nociception in the formalin test. In the anxiolytic test, the patterns of transition in the two arms of the EPM and in the light/dark box were assessed. Results: JB (10–200 mg/kg, p.o.) significantly inhibited the inflammatory pain produced by acetic acid as evidenced by decreased number of abdominal constrictions in comparison with the control. It also shows higher potency in suppressing the inflammatory pain associated with the second phase of the formalin test. However, JB did not exhibit anxiolytic properties nor modify the pain behavior in the tail immersion test. Conclusions: The results obtained from this study suggest that Jobelyn® might be efficacious against inflammatory pain and further support its recommendation for the management of pain with inflammation as the underlying factor.