Solomon Umukoro

Evaluation of the anti-diabetic properties of Mucuna pruriens seed extract

OBJECTIVE To explore the antidiabetic properties of Mucuna pruriens(M. pruriens). METHODS Diabetes was induced in Wistar rats by single intravenous injection of 120 mg/kg of alloxan monohydrate and different doses of the extract were administered to diabetic rats. The blood glucose level was determined using a glucometer and results were compared with normal and untreated diabetic rats. The acute toxicity was also determined in albino mice. RESULTS Results showed that the administration of 5, 10, 20, 30, 40, 50, and 100 mg/kg of the crude ethanolic extract of M. pruriens seeds to alloxan-induced diabetic rats (plasma glucose > 450 mg/dL) resulted in 18.6%, 24.9%, 30.8%, 41.4%, 49.7%, 53.1% and 55.4% reduction, respectively in blood glucose level of the diabetic rats after 8h of treatment while the administration of glibenclamide (5 mg/kg/day) resulted in 59.7% reduction. Chronic administration of the extract resulted in a significant dose dependent reduction in the blood glucose level (P<0.001). It also showed that the antidiabetic activity of M. pruriens seeds resides in the methanolic and ethanolic fractions of the extract. Acute toxicity studies indicated that the extract was relatively safe at low doses, although some adverse reactions were observed at higher doses (8-32 mg/kg body weight), no death was recorded. Furthermore, oral administration of M. pruriens seed extract also significantly reduced the weight loss associated with diabetes. CONCLUSIONS The study clearly supports the traditional use of M. pruriens for the treatment of diabetes and indicates that the plant could be a good source of potent antidiabetic drug.

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.

Antidepressant activity of methyl jasmonate, a plant stress hormone in mice.

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.

Evaluation of the anti-stress and anticonvulsant activities of leaf extract of Alchornea cordifolia in mice.

AIM OF THE STUDY The extract of the leaves of Alchornea cordifolia (AC) is extensively used in ethnomedicine for ulcers, rheumatic pains, febrile convulsions and for enhancing physical performance. In this study, the anti-stress and anticonvulsant activities of the aqueous leaf extract of Alchornea cordifolia were investigated in mice. MATERIALS AND METHODS The anti-stress activity was assessed based on the ability of the extract to alter the duration of immobility, in the forced swim endurance test, whilst a picrotoxin-treated animal, was employed as the model for convulsive seizures. RESULTS The extract (100-400 mg/kg) given orally was found to significantly (p<0.05) reduce the duration of immobility, which suggest an anti-stress/anti-fatigue property. However, AC when tested at doses between 100 and 400 mg/kg did not prevent convulsions induced by picrotoxin in mice. The acute toxicity study carried out in mice revealed that the extract was well tolerated by the animals, as no death was observed at oral doses of 500-4000 mg/kg. CONCLUSIONS The results of this preliminary study provide evidence, which may support the use of Alchornea cordifolia against stress or fatigue in ethnomedicine.

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.

Evaluation of adaptogenic-like property of methyl jasmonate in mice exposed to unpredictable chronic mild stress.

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.

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.

Antipsychotic property of solvent-partitioned fractions of Lonchocarpus cyanescens leaf extract in mice

Abstract Background: This study was carried out to evaluate the antipsychotic property of solvent-partitioned fractions of the leaf extract of Lonchocarpus cyanescens (LC), a reputable medicinal plant used in folk medicine for the treatment of mental illnesses in Nigeria. Methods: The n-hexane fraction, ethyl acetate fraction (EAF), and aqueous ethanol fraction (AEF) of LC were tested for antipsychotic property based on the antagonism of stereotypy induced by apomorphine (APO). Antagonism of hyperactivity and lethality in aggregated mice induced by amphetamine (AMPH) were further employed for screening the antipsychotic effect of the fractions. EAF was tested for catalepsy utilising the horizontal plane paradigm. Thin-layer chromatography (TLC) was used to screen EAF for the presence of secondary metabolites. Results: AEF (100–400 mg/kg) significantly (p<0.05) suppressed stereotypy induced by APO (2 mg/kg, intraperitoneal [IP]) in comparison with control, suggesting antipsychotic activity. However, EAF (200 mg/kg, IP) was most potent in inhibiting the stereotypic effect of APO. EAF was also the most active in antagonising AMPH-induced hyperactivity and in protecting against death caused by AMPH in grouped mice. However, in contrast to haloperidol, EAF did not produce cataleptic behaviour in the horizontal plane paradigm. The TLC analysis revealed that EAF contains several compounds, with some of them having Rf values similar to that of haloperidol, which suggests the presence of active substances with the same chemical structural identity. Conclusions: These findings suggest that EAF contains the major active constituent(s) mediating the antipsychotic property of LC and further support its use for the management of psychosis in traditional medicine.

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.