Adegbuyi Oladele Aderibigbe

Studies on neuropharmacological profile of ethanol extract of Moringa oleifera leaves in mice

ETHNOPHARMACOLOGICAL RELEVANCE Moringa oleifera (family Moringaceae), commonly called Horseradish or tree of life, is traditionally used for the treatment of epilepsy and neurologic conditions. AIM OF THE STUDY The objective of this study is to investigate the neurobehavioural and anticonvulsant properties of the ethanol extract from the leaves of Moringa oleifera. MATERIALS AND METHODS Neurobehavioural properties were evaluated using the open field, hole board, Y-maze, elevated plus maze (EPM) and pentobarbitone-induced hypnosis. Pentylenetetrazole (leptazol), picrotoxin and strychnine induced convulsion tests were used to investigate the anti-convulsive actions of Moringa oleifera. RESULTS The result showed that the extract (250-2000mg/kg) caused a significant dose-dependent decrease in rearing, grooming, head dips and locomotion (P<0.001). It also enhanced learning and memory and increased anxiogenic effect. In addition, the extract (2000mg/kg) protected mice against pentylenetetrazol induced convulsion, but has no effect on picrotoxin and strychnine induced convulsion. The effects of the extract in the various models were comparable to those of the standard drugs used except in Y-maze, EPM and picrotoxin and strychnine induced convulsion. The LD50 obtained for the acute toxicity studied using oral route of administration was >6.4g/kg. CONCLUSION The findings from this study suggest that the ethanol extract of Moringa oleifera leaves possesses CNS depressant and anticonvulsant activities possibly mediated through the enhancement of central inhibitory mechanism involving release γ-amino butyric acid (GABA). The results partially justified the traditional use of the extract for the treatment of epilepsy.

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.

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.

Neuroprotective effects of the ethanol stem bark extracts of Terminalia ivorensis in ketamine-induced schizophrenia-like behaviors and oxidative damage in mice.

Abstract Context: Schizophrenia is a heterogenous neurological disorder, which has been hypothetically linked to oxidative imbalance and associated behavioral perturbations. Preliminary evidence from animal models predictive of human psychosis suggests that Terminalia ivorensis A. Chev. (Combretaceae) has antipsychotic-like activity in mice. Objective: This study investigates the neuroprotective property of the ethanol stem bark extracts of T. ivorensis (EETI) in reversal treatment of ketamine-induced schizophrenia-like behaviors and oxidative alteration in adult male Swiss albino mice. Materials and methods: Animals were divided into six treatment groups (n = 5). Animals received distilled water or ketamine (20 mg/kg) once daily intraperitoneally (i.p.) for 14 days, and from the 8th to the 14th day, they were treated with EETI (125, 250 or 500 mg/kg), risperidone (RIS) or vehicle orally once daily. Behaviors related to positive (locomotor activity) and cognitive (Y maze) symptoms of schizophrenia were assessed. Glutathione (GSH) levels, superoxide dismutase (SOD) and catalase (CAT) activities, including malondialdehyde (MDA) concentration were measured in mice whole brains. Result: The LD50 of EETI was 2236.06 mg/kg, p.o. body weight. EETI (125, 250 or 500 mg/kg, p.o.) demonstrated significant (p < 0.05) inhibition of ketamine-induced hyperlocomotion and cognitive dysfunction. The extract decreased MDA concentration (39.0, 62.6 and 67.5%) in a dose-dependent manner. Moreover, EETI significantly (p < 0.05) reversed the depletion of GSH, and increased activities of SOD and CAT in brain tissues. Discussion and conclusion: These findings suggest that EETI probably exert its antipsychotic-like activity, via a neuroprotective compensatory mechanism of action, and as such, could be relevant in the management of schizophrenia.

Anti-nociceptive activity of the crude extract of Myrianthus arboreus P. Beauv (Cecropiaceae) in mice.

ETHNOPHARMACOLOGICAL RELEVANCE Myrianthus arboreus P. Beauv (Cecropiaceae) is a shrub or a tree plant widely distributed in Tropical Africa. In the South Eastern part of Nigeria, the leaves are used in traditional medicine as an analgesic for muscular pains, and also as an enema to relieve pain in the back and loins. Although no scientific study has been performed to validate its traditional use in pain management, this study therefore aims at investigating the anti-nociceptive activity of M. arboreus leaves extract in mice. MATERIALS AND METHODS Anti-nociceptive activity of M. arboreus was investigated using acetic acid induced writhing, formalin induced paw licks, hot plate, and tail flick tests. Acute toxicity was determined using a slightly modified Lorkes method. RESULTS The extract of M. arboreus produced a significant dose-dependent [F (4, 20)=13.48 p<0.001] inhibition of abdominal writhings induced by acetic acid. In the formalin paw licking test, it produced a significant dose-dependent inhibition of neurogenic and inflammatory pain [F (4, 17.5)=60.13 p<0.001]. It also produced a significant dose dependent [F (4, 20)=30.5 p<0.001; F (4, 20)=0.321 p<0.0001] prolongation of the latency and reaction time in the hot plate and tail immersion tests. Peak effect was observed at the highest dose (40 mg/kg). LD50 of the plant was found to be 894 mg/kg. CONCLUSION M. arboreus possesses potent antinociceptive activity mediated centrally and peripherally, an effect which may justify its traditional use in the management of pain.

Morin Pretreatment Attenuates Schizophrenia-Like Behaviors in Experimental Animal Models

OBJECTIVES Morin is a naturally occurring flavonoid with strong anti-oxidant and anti-inflammatory properties. Studies have shown that flavones modulate neurotransmission through enhancement of gamma amino butyric acid activity in the central nervous system; which led to the hypothesis that they could exert tranquilizing effects in rodents. Hence, this study was designed to evaluate the antipsychotic effect of morin on experimental animal models. METHODS The antipsychotic effect of morin (25, 50 and 100 mg/kg) administered intraperitoneally (i.p.) was assessed on novelty-induced locomotion, apomorphine-induced stereotypy, ketamine-induced stereotypy, ketamine-induced hyperlocomotion and ketamine-enhanced immobility in forced swim test (FST). Catalepsy and rota rod tests were also carried out to evaluate the extrapyramidal side effects of morin. RESULTS Morin (25, 50 and 100 mg/kg, i.p.) pretreatments significantly (p<0.05) demonstrated anti-schizophrenia-like behavior by inhibiting ketamine-induced hyperlocomotion in mice. Moreover, morin (50 and 100 mg/kg, i.p.) significantly (p<0.05) reduced spontaneous locomotor activity. Also, morin suppressed apomorphine-induced stereotypy and ketamine-induced stereotypy. The increase in immobility in FST due to ketamine administration was reduced by morin in a significant dose-dependent manner. Furthermore, the antipsychotic activity of morin was not associated with extrapyramidal side effects, as evidenced by decreased decent latency and increased motoric coordination and performance in mice. CONCLUSION The results of the study revealed that morin demonstrated antipsychotic-like property devoid of extrapyramidal side effects in experimental animal models and may be beneficial in the treatment of schizophrenia-like behaviors; particularly in patients with behavioral hyperactivity and negative symptoms.

Antinociceptive property of Olax subscorpioidea Oliv (Olacaceae) extract in mice.

ETHNOPHARMACOLOGICAL RELEVANCE Olax subscorpioidea is a shrub or tree found in Nigeria, and other parts of Africa. It is used in the management of inflammatory disorder, mental illness, convulsion, pain, and cancer. However, there is dearth of information on scientific basis for its folkloric use in the management of pain. Therefore, the study was designed to investigate the antinociceptive property of the extract of Olax subscorpioidea (EOS) leaves in mice. MATERIALS AND METHODS Antinociceptive activity of EOS (12.5-50 mg/kg, i.p.) was investigated using acetic acid induced abdominal writhing, tail immersion, hot plate and formalin tests. RESULTS Extract of Olax subscorpioidea produced significant dose dependent inhibition of writhing frequency [F(4,20)=155.9, p<0.0001] and significant dose dependent inhibition of neurogenic and inflammatory pains [F(4,20)=116.7, p<0.0001; F(4,20)=40.05, p<0.0001]. It also produced a significant dose dependent prolongation of the latent period and reaction times in tail immersion and hot plate tests in mice [F(4,20)=19.49, p<0.0001; F(4,20)=97.95, p<0.0001]. CONCLUSION Olax subscorpioidea possessed potent analgesic action, mediated centrally and peripherally, thus justifying its use in the management of pain.

Jobelyn® pretreatment ameliorates symptoms of psychosis in experimental models.

Abstract Background: Psychosis is a chronic neurological disorder and it remains a major medical and social problem in most African countries. Individuals with psychotic illness in this region tend to seek help from traditional medical practitioners, who prescribe herbal remedies as alternative forms of treatment for the disease. Jobelyn® (JB) is a commercial polyherbal formulation that has been acclaimed to show beneficial effects in neurological disorders. However, its usefulness in psychosis has not been scientifically validated. Thus, this study was undertaken to evaluate its effects on animal models predictive of human psychosis. Methods: Antipsychotic activity of JB was assessed based on the inhibition of stereotyped behavior induced by amphetamine or apomorphine in mice. Amphetamine-induced hyperactivity and lethality in aggregated mice were additional tests employed to further evaluate the antipsychotic property of JB. The effect of JB on catalepsy was also assessed, using the inclined plane paradigm. Results: JB (5–50 mg/kg, p.o.) significantly (p<0.05) inhibited stereotypy induced by amphetamine (10.0 mg/kg, i.p.) or apomorphine (1 mg/kg, i.p.), which suggests antipsychotic activity. Furthermore, JB (5–50 mg/kg, p.o.) reduced lethality in aggregated mice and inhibited hyperactivity induced by amphetamine, respectively. However, JB (5–50 mg/kg, p.o.) did not cause cataleptic behavior, as it failed to alter the duration of stay of the animals on the inclined plane. Conclusions: Taken together, these findings suggest that JB exhibits antipsychotic-like activity, devoid of the adverse effect of cataleptic behavior, and may offer some beneficial effects in the symptomatic relief of psychotic ailments.

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.

Pharmacological Evaluation of Central Nervous System Effects of Ethanol Leaf Extract of Olax Subscorpioidea in Experimental Animals.

BACKGROUND Olax subscorpioidea Oliv. (Olacaceae) is a medicinal plant used in folk medicine in the management of pain, mental illness, and convulsion. We evaluated neurosedative and anticonvulsant properties of the ethanol leaf extract of O. subscorpioidea (ELEOS). METHODS Effects of ELEOS (3.125, 6.25, 12.5, 25 mg/kg) on novelty-induced behaviors were determined using open field test. Anxiolytic effect of ELEOS (3.125, 6.25, 12.5, 25 mg/kg) was assessed using hole-board and elevated-plus maze paradigms. The effect of O. subscorpioidea on pentobarbitone sleeping time was also investigated. Anticonvulsant property of ELEOS (12.5-50 mg/kg) was evaluated using pentylenetetrazole, picrotoxin and strychnine-induced convulsions assays. The extract was administered once intraperitoneally. RESULTS The LD50 of ELEOS was 300 mg/kg. ELEOS (3.125, 6.25, 12.5, 25 mg/kg) significantly reduced rearing (99.8±2.8, 76.2±2.9, 37.4±1.2, 5.8±0.8) and grooming (48.0±3.6, 33.8±2.9, 25.4±1.6, 7.6±0.8) as compared with controls (185.8±5.1; 63.8±4.3). Treatment with ELEOS (3.125, 6.25, 12.5, 25 mg/kg) significantly reduced head-dipping on hole-board (10.6±1.9, 8.8±1.2, 7.2±0.9, 6.0±1.1) as compared with control (27.8±1.5). However, there was no anxiolytic effect on EPM. ELEOS (12.5, 25, 50 mg/kg) significantly prolonged pentobarbitone-induced sleeping time (43.0±1.4, 51.0±1.2, 61.0±1.8) as compared with control (31.0±0.7). At 50 mg/kg, ELEOS significantly prolonged onset of seizure (2.72±2.07) and latency to death (9.20±1.24) as compared with controls (0.54±0.02; 2.00±0.44) in pentylenetetrazole-induced convulsions with no effect on picrotoxin and strychnine-induced convulsions. CONCLUSION The ELEOS is sedative and has mild anticonvulsant activity and this study supports pharmacological basis for its use in the management of mental illness and convulsion.