Evidence of alterations in brain structure and antioxidant status following 'low-dose' monosodium glutamate ingestion.

OBJECTIVE: The study investigated the effects of low dose monosodium glutamate (MSG) on the brain, with a view to providing information on its effects on neuronal morphology and antioxidant status in mice. METHODOLOGY: Sixty male mice (20-22 g) were divided into six groups of ten animals each. Vehicle (distilled water), a standard (l-glutamate at 10mg/kg body weight) or MSG (10, 20, 40 and 80mg/kg body weight) were administered orally for 28days. Sections of the cerebrum, hippocampus and cerebellum were processed and stained using hematoxylin and eosin, examined under a microscope and captured images analysed. Plasma and brain levels of glutamate, glutamine, and antioxidants were assayed. Data obtained were analysed using descriptive and inferential statistics. RESULTS: MSG ingestion did not significantly alter body weight. Relative brain weight increased at 40 and 80mg/kg compared to vehicle. Histological and histomorphometric changes consistent with neuronal damage were seen in the cerebrum, hippocampus and cerebellum at 40 and 80mg/kg. Plasma glutamate and glutamine assay showed significant increase at 40 and 80mg/kg while no significant difference in total brain glutamate or glutamine levels were seen. Levels of brain superoxide dismutase and catalase decreased with increasing doses of MSG, while nitric oxide (NO) increased at these doses. CONCLUSION: The study showed morphological alterations consistent with neuronal injury, biochemical changes of oxidative stress and a rise in plasma glutamate and glutamine. These data therefore still support the need for cautious consideration in the indiscriminate use of MSG as a dietary flavor enhancer.

Influence of a Nigerian honey on CYP3A4 biotransformation of quinine in healthy volunteers.

WHAT IS KNOWN AND OBJECTIVES: Some studies, howbeit with conflicting reports, have suggested that consumption of honey has a potential to modulate drug metabolizing enzymes which may result in a honey-drug interaction. Numerous studies have established that honey varies in composition, influenced by the dominant floral, processing and environmental factors. Thus, variation in honey composition may be a contributing factor to the controversial results obtained. No previous drug interaction study has been carried out with any honey from Africa. CYP 3A4 is an important enzyme in drug metabolism studies as it is involved in the metabolism of over 50% of drugs in clinical use and quinine remains very relevant in malaria treatment in the tropics, and we therefore determined whether there is potential drug interaction between a Nigerian honey and quinine, a drug whose metabolism to 3-hydroxyquinine is mediated majorly by CYP3A4. METHODS: In a three-phase randomized crossover study with a washout period of 2 weeks between each treatment phase, ten (10) healthy volunteers received quinine sulphate tablet (600 mg single dose) alone (phase 1) or after administration of 10 ml of honey (Phase 2) and 20 mL of honey (Phase 3) twice daily for seven (7) days. Blood samples were collected at the 16th hour post-quinine administration in each phase, and quinine and its major metabolite, 3-hydroxyquinine, were analysed using a validated HPLC method. RESULTS: After scheduled doses of honey, the mean metabolic ratios of quinine (3-hydroxyquinine/quinine) increased by 24·4% (with 10 mL of honey) and reduced by 23·9% (with 20 mL of honey) when compared to baseline. These magnitudes of alteration in the mean metabolic ratios were not significant (P > 0·05; Friedman test). The geometric mean (95% CI) for the metabolic ratio of quinine before and after honey intake at the two dose levels studied was 0·82 (0·54, 1·23) and 1·29 (0·96, 1·72), respectively, and were also not significant (P = 0·296 and 0·081 respectively; Student's t-test). WHAT IS NEW AND CONCLUSION: This is a pioneer study on the effect of Nigerian/African honey on quinine metabolism. The findings indicated that low and high doses of honey did not significantly affect metabolism of quinine to 3-hydroxyquinine. This suggests that CYP3A4 activity is not significantly altered following low or high dose of honey, as CYP3A4 has been reported to be responsible for the conversion of quinine to 3-hydroxyquinine. In conclusion, the outcome of this study suggests that there may be no potential significant metabolic interaction between Nigerian honey and quinine administration.

Neuropharmacological profile of aqueous extract of Anaphe venata larva (Notondotidae) in rats.

Consumption of Anaphe larva had been reported to cause seasonal ataxia and impaired consciousness. Therefore this study examined the neuropharmacological and mechanism(s) of action of aqueous extract of Anaphe venata in rats. Behavioural effects namely rearing, stretching, sniffing and ataxia were determined after the intraperitoneal administration of aqueous extract of Anaphe larva in rats. Animals were divided into groups and graded doses (100, 200 and 400 mg/kg, i.p.) of extract were administered. The control group was administered normal saline (vehicle). The effects of scopolamine (3 mg/kg, i.p.), flumazenil (2 mg/kg, i.p.), naloxone (2.5 mg/kg, i.p.), and thiamine (1 mg/kg, i.p.) on the observed behavioral changes were also examined. The effects of the extract administered intraperitoneally at a dose of 200 mg/kg on the amphetamine-induced stereotypy and locomotion were evaluated. Aqueous anaphe extract induced significant (p< 0.01) stretching and ataxia behavioural effects while it inhibited rearing behaviour when compared with the vehicle-treated group. However, it had no significant effect on sniffing behaviour. Scopolamine reversed all the effects of the extract on rearing, stretching and ataxia. Both Flumazenil and naloxone only reversed the effects of the extract on stretching and ataxia-induced behaviours significantly. However, thiamine potentiated both stretching and ataxia-induced behaviours. The extract inhibited the amphetamine-induced stereotype behaviour and locomotion. In conclusion, these results showed that these anaphe-induced behavioural effects are mediated via cholinergic, GABAergic, opioidergic and dopaminergic receptor systems with strong muscarinic-cholinergic receptors involvement in ataxia-induced behaviour. We therefore suggest that muscranic-cholinergic like drugs may be of benefit in the management of patients that present with clinical condition of seasonal ataxia.

Anaphe venata larva extract-induced purposeless chewing in rats: the role of cholinergic, GABAergic and opioid systems.

Seasonal ataxia was reported in humans following the consumption ofAnaphe venata larva as protein supplement in diet and altered motor function in rodents when the extract was administered intraperitoneally. In this study we investigated the effect of the crude aqueous and Phosphate Buffer Saline (PBS) extracts of this larva on altered spontaneous rat behavior in a novel environment particularly chewing behaviour, with a view to determine the mechanism(s) involved in these behavioural alteration. Animals were randomly assigned into four groups (n = 6-12 per group) and graded doses of aqueous and PBS extracts (100-400 mg/kg) were administered dissolved in saline intraperitoneally (i.p.) to each animal in the experimental groups. The control group received an equivalent volume of saline. Behavioral scores were recorded for a period of 30 minutes after the administration of saline or extract. The role of various receptors in the extract induced chewing was evaluated using known receptor agonist/antagonists. Results revealed a significant increase in purposeless chewing (F (7, 95) = 7.85; p <0.05) by the aqueous extract compared to saline control at all dose levels, which was significantly attenuated by scopolamine (3 mg/kg, i.p) and thiamine (1 mg/kg, i.p) respectively (p <0.05); while flumazenil (2 mg/kg, i.p) and naloxone (2.5 mg/kg, i.p) did not alter the induced purposeless chewing behaviour. Also, administration of PBS induced a significant (F (7, 95) = 6.11; p <0.05) increase in chewing behaviour but only at 400 mg/kg dose level which was attenuated by scopolamine (3 mg/kg, i.p); while flumazenil (2 mg/kg, i.p), naloxone (2.5 mg/kg, i.p), and thiamine (1 mg/kg, i.p) potentiated purposeless chewing behaviour respectively. It may therefore be concluded from this study that Anaphe extract-induced purposeless chewing behaviour in rat is mediated via the activation of cholinergic neurotransmission which is modulated by GABAergic and opioid receptor systems.

Functional reactivity of the dopaminergic system following acute and chronic ketamine treatments.

This study examined the effects of acute (15 mg/kg, i.p.) and chronic subanesthetic (15 mg/kg, i.p., t.i.d, for 6 days) doses of ketamine [a noncompetitive N-methyl-D: -aspartate (NMDA) receptor antagonist] on amphetamine (presynaptic dopamine releasing agent; 10 mg/kg, i.p.) and apomorphine (a D(2) receptor agonist; 1 mg/kg, i.p.)-induced stereotyped behaviors. The effect of acute and chronic ketamine on haloperidol (a D(2) receptor antagonist; 1.6 mg/kg, i.p.)-induced catalepsy was also examined. Acute ketamine and chronic ketamine pretreatment increased amphetamine-induced stereotyped sniffing and locomotion compared with control groups. Acute ketamine significantly increased apomorphine-induced stereotyped sniffing. However, chronic ketamine had no significant effect on apomorphine-induced stereotyped sniffing. Acute, but not chronic ketamine treatment abolished haloperidol-induced catalepsy. The increase in amphetamine-induced stereotyped behaviors and the reversal of haloperidol-induced catalepsy by acute ketamine suggest that blockade of NMDA receptors by ketamine facilitates dopaminergic transmission. The absence of significant effect of chronic ketamine on apomorphine-induced stereotyped sniffing and haloperidol-induced catalepsy suggests that chronic ketamine does not modulate postsynaptic dopaminergic D(2) receptors. It is suggested that chronic ketamine increased amphetamine-induced behaviors by causing hypersensitivity of presynaptic dopamine releasing mechanisms on dopaminergic terminals.

Antinociceptive and antiinflammatory effects of essential oil of Dennettia tripetala G.Baker (Annonaceae) in rodents.

In this study we evaluated the analgesic and anti-inflammatory activities of the essential oil (EO) of the fruits of Dennettia tripetala in rodents. The plant is a tropical African plant and the fruits are commonly eaten as spices and consumed as a stimulant, and its various parts are used in the treatment of fever, cough and as anti-emetics.The analgesic effects of the oil was assessed in mice using the hot plate, acetic acid-induced writhings and formalin test, while carrageenan-induced paw oedema was used to study the antiinflammatory effects in rats. The EO at 25-50 mg/kg exhibited significant (p<0.05) antinociceptive effects comparable to a potent opioid agonist, morphine (10 mg/kg) and non-steroidal anti-inflammatory drugs such as, aspirin (100 mg/kg) and indomethacin (80 mg/kg). The antinociceptive effect of the EO was also blocked by naloxone (2 mg/kg) in all the models used. The EO demonstrated significant (p<0.05) anti-inflammatory effect in the carrageenan-induced paw oedema model of inflammation that is also comparable to dexamethasone (1 mg/kg) The results showed that the essential oil of D. tripetala possesses significant antinociceptive and antiinflammatory effects in the animal models used. The results also suggest that the analgesic effects may be mediated both centrally as well as peripherally, while the antiinflammatory activity may be effective in both early and late phases of inflammation. The results obtained may therefore be used to rationalize the use of the plant in the treatment of pain and fever in traditional medicine.

Antinociceptive and antiinflammatory effects of essential oil of Dennettia Tripetala G. Baker (annonaceae) in Rodents

In this study we evaluated the analgesic and anti- inflammatory activities of the essential oil (EO) of the fruits of Dennettia tripetala in rodents. The plant is a tropical African plant and the fruits are commonly eaten as spices and consumed as a stimulant, and its various parts are used in the treatment of fever, cough and as anti-emetics. The analgesic effects of the oil was assessed in mice using the hot plate, acetic acid-induced writhings and formalin test, while carrageenan-induced paw oedema was used to study the antiinflammatory effects in rats. The EO at 25-50 mg/kg exhibited significant (p0.05) antinociceptive effects comparable to a potent opioid agonist, morphine (10 mg/kg) and non-steroidal anti-inflammatory drugs such as, aspirin (100 mg/kg) and indomethacin (80 mg/kg). The antinociceptive effect of the EO was also blocked by naloxone (2 mg/kg) in all the models used. The EO demonstrated significant (p0.05) anti-inflammatory effect in the carrageenan-induced paw oedema model of inflammation that is also comparable to dexamethasone (1 mg/kg) The results showed that the essential oil of D.tripetala possesses significant antinociceptive and antiinflammatory effects in the animal models used. The results also suggest that the analgesic effects may be mediated both centrally as well as peripherally, while the antiinflammatory activity may be effective in both early and late phases of inflammation. The results obtained may therefore be used to rationalize the use of the plant in the treatment of pain and fever in traditional medicine

Hypoglycaemic constituents of Stachytarpheta cayennensis leaf.

The aqueous infusion (tea) of Stachytarpheta cayennensis leaves is used ethnomedically in Peru, Nigeria and other tropical countries for the management of diabetes. Oral administration (p. o.) of aqueous (125 mg/kg) and methanolic (2000 mg/kg) extracts of the leaves to alloxan-diabetic rats showed significant blood glucose reductions by 43 and 53%, respectively, at the end of a 4 hour period similar to the strong effect of glibenclamide (5 mg/kg, P. O.). The methanolic extract was successively partitioned into ethyl acetate, butanol and water fractions, and the same test showed that the butanol fraction (2000 mg/kg) had the highest (50%) hypoglycaemic activity at 4 hours after oral administration. It was also the most active fraction when tested in vitro [insulin release from an insulin secreting cell line (INS-1)] and was also active in normal rats and rats made hyperglycaemic by a glucose load. Its activity was comparable to that of glibenclamide (positive control) in these models. This active butanol fraction was subjected to chromatographic subfractionation; some subfractions reduced hyperglycaemia in alloxan-diabetic rats to 60 and 78% and induced insulin release from the INS-1 cells; other subfractions, however, gave hyperglycaemic activities IN VIVO and inhibition of insulin release from the INS-1 cells. Three major compounds of the butanol fraction were isolated and characterised as 6beta-hydroxyipolamide, ipolamide and isoverbascoside; they increased insulin secretion from INS-1 cells to 125, 128 and 127%, respectively, whereas glibenclamide increased insulin secretion to 157%. The results justify the ethnomedical use of the plant in the management of diabetes and suggest that the butanol fraction and some of its isolated constituents mediate their actions primarily by stimulating insulin release directly.