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 Alzheimer's 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-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.

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 Alzheimer's 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.

Anti-psychotic and sedative effect of calcium channel blockers in mice.

Calcium channel blockers (CCBs) are widely used as therapeutic agents, for the treatment of cardiovascular disorders. However, the discovery that CCBs bind to various regions of the brain suggest that they might also offer some beneficial effects in the treatment of neuropsychiatry disorders. This study was carried out to evaluate the anti-psychotic and sedative effects of two notable calcium channel blockers, verapamil and nifedipine in mice. The anti-psychotic effects of the CCBs were studied in the animal model of amphetamine-induced stereotyped behavioral disorders. The sedative effect was assessed utilizing the prolongation of the time of sleep, induced by thiopentone. The ability of CCBs to produce catalepsy in mice was also evaluated in the study. Graded doses of verapamil (5.0-20.0 mg/kg, i.p) significantly (p<0.05) suppressed stereotyped behaviour induced by amphetamine (10.0 mg/kg, i.p). In contrast, nifedipine (5.0-20.0 mg/kg, i.p) did not exhibit anti-psychotic effect, as it could not significantly reduce stereotypy caused by amphetamine. In the test for sedation, both verapamil (5.0-20.0 mg/kg, i.p) and nifedipine (10.0-20.0 mg/kg) significantly (p<0.05) prolonged the sleeping time induced by thiopentone (50.0 mg/kg, i.p). However, neither verapamil (5.0-20.0 mg/kg, i.p.) nor nifedipine (5.0-20.0 mg/kg, i.p.) at the tested doses produced any cataleptic behaviour in the animals. The results of the study suggest that verapamil has both anti-psychotic and sedative effects without inducing the side effect of catalepsy and might be relevant in the treatment of psychosis.

Effect of Aframomum melegueta. Seed Extract on Castor Oil-Induced Diarrhea.

The effect of the aqueous (aq) seed extract of Aframomum melegueta. K. Schum. (Zingiberaceae) on castor oil-induced diarrhea, intestinal fluid secretion, and gastrointestinal transit was investigated in the study. Castor oil (10 ml/kg, p.o.) induced copious diarrhea in all rats 3 h after treatment. Furthermore, it produced a significant increase in the volume of intestinal fluid secretion in rats and also enhanced intestinal transit in mice. The aq seed extract of A. melegueta. (100-500 mg/kg, p.o.) offered significant protection against diarrhea induced by the oil. At a dose range of 250-500 mg/kg, the extract reduced significantly the volume of fluid secretion in castor oil-treated rats. At these doses, it also demonstrated a significant antitransit activity in a dose-related manner. Acetylsalicylic acid (100 mg/kg, p.o.) delayed diarrhea and reduced the number of animals with diarrheal droppings to 20%. At the same dose level, acetylsalicylic acid reduced significantly the volume of intestinal fluid secretion but lacked antitransit property in castor oil-treated animals. N.-Nitro-L-arginine methyl ester (L-NAME) (2.5-10 mg/kg, i.p.) dose-dependently reduced the number of animals with diarrhea. At 50 mg/kg i.p., it offered 100% protection against diarrhea induced by the oil. Furthermore, L-NAME (10 mg/kg, i.p.) significantly inhibited both the intestinal fluid secretion and gastrointestinal transit induced by castor oil. However, L-NAME (10 mg/kg, i.p.) did not significantly modify the antidiarrheal effect of A. melegueta.. L-Arginine, a substrate of nitric oxide synthase or isosorbide dinitrate, a nitric oxide donor, did not alter the effect of A. melegueta. on diarrhea. Ascorbic acid (100 mg/kg, p.o.) and α.-tocopherol (20 mg/kg, p.o.) reduced the number of animals with diarrhea to 80% and 70%, respectively. However, they both lacked significant activities on intestinal fluid secretion and gastrointestinal transit induced by castor oil. The combination of ascorbic acid (100 mg/kg, p.o.) or α.-tocopherol (20 mg/kg, p.o.) with A. melegueta. (500 mg/kg) offered higher protection against diarrhea than the extract alone. Considering these results together, it may be inferred that Aframomum melegueta. seed extract may be a useful antidiarrheal agent.