Antihyperglycaemic activity of the stem-bark extract of Tamarindus indica L. on experimentally induced hyperglycaemic and normoglycaemic Wistar rats.

Diabetes is the most common endocrine disease and its prevalence is reaching epidemic proportion worldwide. In 2002, WHO Expert Committee on diabetes mellitus recommended an urgent and further evaluation of the folkloric methods of managing the disease. In response to this recommendation, several medicinal plants are currently being investigated for their hypoglycaemic activity and one of such plants is Tamarindus indica. Tamarindus indica is a slow growing tree that is resistant to strong winds and perennial. The stem-bark extract of the plant is used locally for the management of diabetes. The stem-bark extract of Tamarindus indica L. was investigated for its hypoglycemic action on experimentally induced hyperglycaemic Wistar rats using a single dose of alloxan monohydrate (150 mg kg(-1) IP). The oral LD50 of the extract was found to be greater than 5,000 mg kg(-1). Phytochemical screening revealed the presence of carbohydrates, glycosides, saponins, flavonoids, cardiac glycosides, tannins, alkaloids and triterpenes. The 1000 mg kg(-1) dose of the extract lowered the blood glucose level significantly (p < 0.05) at the 4th, 8th and 16th h. The 500 mg kg(-1) lowered the BGL significantly (p < 0.05) throughout the study. In the oral glucose load method the 1000 mg kg(-1) dose of the extract significantly (p < 0.05) lowered elevated blood glucose at the 3rd and 5th. The 500 mg kg(-1) lowered the blood glucose from the 1st to the 5th, while the 250 mg kg(-1) also lowered the blood glucose level but only significantly at the 5th h. The extract is practically non toxic when administered orally. The stem-bark extract of Tamarindus indica Linn significantly lowered elevated Blood Glucose concentration (BGL) in the experimental animal models, while the crude extract was able to prevent an elevation in BGL when used in the oral glucose load model.

Evaluation of the antipsychotic potential of aqueous fraction of Securinega virosa root bark extract in mice.

Securinega virosa (Roxb ex. Willd) Baill. is a plant which is commonly used in African traditional medicine in management of mental illness. Previous study showed that the crude methanolic root bark extract of the plant possesses antipsychotic activity. In this study, the antipsychotic potential of the residual aqueous fraction of the plant was evaluated using two experimental models, apomorphine induced stereotypic climbing behaviour and swim induced grooming, all in mice. The effect of the fraction on haloperidol-induced catalepsy was also evaluated. The fraction significantly reduced the mean climbing score at the highest dose tested (500 mg/kg). In the swim-induced grooming test, the fraction significantly and dose-dependently (125-500 mg/kg) decreased the mean number and mean duration of swim-induced grooming activity in mice. Similarly, the standard haloperidol (1 mg/kg) significantly (p < 0.001) decreased the mean grooming episodes and duration. However, the fraction did not significantly potentiate haloperidol-induced catalepsy. These results suggest that the residual aqueous fraction of methanol root bark extract of Securinega virosa contains biological active principle with antipsychotic potential.

Psychopharmacological properties of saponins from Randia nilotica stem bark.

CONTEXT: Decoctions of Randia nilotica Stapf. (Rubiaceae) have been used in the Nigerian traditional medicine for the management of epilepsy, anxiety, depression and psychosis for many years and their efficacies are widely acclaimed among the rural communities of Northern Nigeria. OBJECTIVE: The aim of this study is to establish whether the saponins present in R. nilotica are responsible for its acclaimed beneficial effects in Nigerian traditional medicine. MATERIALS AND METHODS: The behavioural properties of the saponin-rich fraction (SFRN) of R. nilotica stem bark were studied on hole-board, diazepam-induced sleep, rota-rod and beam-walking in mice. The anticonvulsant properties of SFRN were also examined on maximal electroshock, pentylenetetrazole- and strychnine-induced seizures in mice. RESULTS: The intraperitoneal LD50 of SFRN in mice and rats were estimated to be 11.1 and 70.7 mg/kg, respectively. SFRN significantly prolonged the duration of diazepam-induced sleep; diminished head dip counts in the hole-board test and protected mice against maximal electroshock seizures. SFRN failed to protect mice against pentylenetetrazole- and strychnine-induced seizures; and had no effect on motor coordination on the rota-rod treadmill at the doses tested. SFRN significantly decreased the number of foot slips in the beam-walking assay in mice with no effect on time to reach the goal box. DISCUSSION AND CONCLUSION: This study provides evidence of the psychopharmacological effects of SFRN, thus supporting further development of the psychoactive components as remedies for epilepsy.

Effect of stavudine-based antiretroviral therapy on the severity of polyneuropathy in HIV/AIDS patients: a preliminary report from Zaria, Northern Nigeria.

BACKGROUND: Stavudine, a nucleoside reverse transcriptase inhibitor, used as first-line antiretroviral drug in many developing countries is said to exacerbate distal symmetrical polyneuropathy in HIV/AIDS patients. OBJECTIVE: To evaluate the severity of distal symmetrical polyneuropathy in HIV/AIDS patients on stavudine-based antiretroviral therapy. METHODS: Two hundred and twenty consecutive HIV-infected antiretroviral-naive adults who were eligible for antiretroviral therapy were studied. Each patient was evaluated using a questionnaire, which contained bio-data and distal neurologic symptoms/signs adapted from the subjective peripheral neuropathy screen and the Leeds assessment of neuropathic symptoms and signs pain score. Patients were then put on stavudine, lamivudine and nevirapine. For three months, after which each patient was re-evaluated using the same protocol. Patients with other risk factors for distal symmetrical polyneuropathy were excluded from the study. RESULTS: Three months of antiretroviral therapy reduced the mean neuropathic symptoms and signs scores from 0.71 ± 0.76 to 0.26 ± 0.47 (P=0.00) and 0.72 ± 0.57 to 0.58 ± 0.55 (P=0.00) respectively. The number of patients with symptoms and signs also reduced from 97.8% to 24.4% and 65.9% to 55.0% respectively while the mean CD4+ count rose from 194.3 ± 80.4 cells per mL to 416.1±191.2 cells per mL of blood. CONCLUSION: Three months of stavudine-based antiretroviral therapy reduces the severity of distal symmetrical neuropathy in HIV/AIDS patients, but more studies are needed to evaluate the long-term neuropathic effect of stavudine on Africans.

Pharmacological studies on siculine syrup. II: effects on smooth, skeletal and cardiovascular muscle preparations.

Earlier pharmacological screening showed that siculine syrup (a traditional herbal remedy purported to be useful in the prevention and treatment of sickle cell pain - crises, due to sickle cell anaemia - SCA) had antisickling and analgesic activities as well as antimicrobial and diuretic effects. SCA is an important haemoglobinopathy in Africa and many other communities/countries worldwide, with relatively high morbidity and mortality. The present study was to determine the effects of the extract on various isolated muscle preparations - smooth, skeletal and cardiovascular. Siculine (4-20 microg/mL), like acetylcholine (40-400 microg/mL), contracted the isolated rat uterus concentration dependently. Similar effects were observed with the guinea-pig ileum and rabbit jejunum (2-20 microg/mL). In contrast to these effects, the direct (muscle) and indirect (nerve) stimulations of rat phrenic nerve-diaphragm were relaxed by siculine (4 and 8 microg/mL) and d-tubocurarine (0.8 microg/mL). Siculine also concentration-dependently decreased both the rate and force of contraction of guinea-pig atria and rabbit heart and also resulted in a fall in cat blood pressure in a manner similar to those of acetylcholine. The possible therapeutic and/or toxicological consequences of these effects including the hypotensive activity is noteworthy since siculine syrup is used by the local population for the prevention and treatment of sickle cell pain crises.

Effect of Nigerian meals on the pharmacokinetics of chlorpropamide in type II diabetic patients.

Food-drug interactions are best evaluated on an individual drug basis, in a group of subjects in a population at risk. This is due to their complex nature, which is a function of type and size of meal, the physical and chemical form of the drug and the time lapse between food intake and drug administration. This work was aimed at investigating the effect of three different Nigerian meals, which are regularly consumed by the three major tribes in Nigeria, on the pharmacokinetics of chlorpropamide, a drug commonly used to treat Type II diabetes in this country. Meal A (maize flour meal) was composed of 81% carbohydrate, 3% protein and 11% fat; meal B (cassava flour meal) was composed of 76% carbohydrate, 3% protein and 15% fat; while meal C (browned yam flour meal) was composed of 85% carbohydrate, 2% protein and 8% fat. The effects of the three meals were investigated by administering each of the meals alone, without the medicinal drug (Treatment I); in Treatment II each meal was administered 30 min following the administration of 250 mg chlorpropamide; in Treatment III the drug was administered together with each of the standard meals. Analysis of the plasma levels of chlorpropamide was performed by high performance liquid chromatography (HPLC). Ingestion of the meal alone (Treatment I) resulted in a significant difference in postprandial plasma glucose levels. The time to maximum plasma chlorpropamide concentration was significantly increased in Treatment III (P < 0.05), while all pharmacokinetic parameters and plasma glucose levels were not significantly altered in Treatment II. Analysis of the results demonstrated a better glycaemic response with meals A and C compared with meal B.

Behavioural effects of the methanolic root bark extract of Securinega virosa in rodents.

Securinega virosa is used traditionally as sedative in children and in mental illnesses. In this study, the behavioral effects of methanolic root bark extract of S. virosa were investigated in mice. The results revealed that the extract significantly (P<0.05) and dose-dependently reduced the onset and prolonged the duration of sleep. The extract significantly (P<0.05) decreased exploratory activity and reduced the rate of apomorphine-induced stereotyped climbing at the doses tested (6.25-25 mg/kg). It also produced a significant and dose-dependent motor coordination deficit in mice at the doses tested (P<0.01). The intraperitoneal median lethal dose in mice was 774.6 mg/kg while the preliminary phytochemical screening revealed the presence of alkaloids, tannins, saponins and flavonoids. These results suggest that methanolic root bark extract of S. virosa contains biologically active principles that are sedative in nature and lend pharmacological credence to the ethnomedical use of the plant.

Euphorbia hirta leaf extracts increase urine output and electrolytes in rats.

Euphorbia hirta is locally used in Africa and Australia to treat numerous diseases, including hypertension and edema. The diuretic effect of the E. hirta leaf extracts were assessed in rats using acetazolamide and furosemide as standard diuretic drugs. The water and ethanol extracts (50 and 100 mg/kg) of the plant produced time-dependent increase in urine output. Electrolyte excretion was also significantly affected by the plant extracts. The water extract increased the urine excretion of Na+, K+ and HCO3-. In contrast, the ethanol extract increased the excretion of HCO3- decreased the loss of K+ and had little effect on renal removal of Na+. Acetazolamide, like the water extract, increased urine output and enhanced the excretion of Na+, K+ and HCO3-. The high-ceiling diuretic, furosemide, increased the renal excretion of Na+ and Cl-; but had no effect on K+ and HCO3- loss. This study suggests that the active component(s) in the water extract of E. hirta leaf had similar diuretic spectrum to that of acetazolamide. These results validate the traditional use of E. hirta as a diuretic agent by the Swahilis and Sukumas.

The effect of single does of rifampicin on the pharmacokinetics of oral nifedipine.

The pharmacokinetic interaction of oral rifampicin (1200 mg) and oral nifedipine (10 mg capsules), given as single doses, was investigated in six healthy volunteers (mean age 28.5 +/- 6.3 years and mean weight 67.0 +/- 4/45 kg). The plasma concentrations of nifedipine was monitored using a HPLC technique, 8 h after pre-treatment, with rifampicin. The mean relative bioavailability of nifedipine following pre-treatment with rifampicin 1200 mg was 35.8% (P < 0.0001). The mean elimination half life (t1/2) of nifedipine decreased from 2.62 to 1.03 h (P < 0.0001); and, the total clearance (ClT) increased from 17.33 to 50.17 ml min-1 kg-1 (P < 0.0001). There were no significant differences in Vd and Tmax. The study suggests that the effect of induction by rifampicin decreases the bioavailability of nifedipine by either increasing the first pass effect or decreasing its oral absorption. The induction also increases the clearance of nifedipine.

Antimalarial drug response of Plasmodium falciparum from Zaria, Nigeria.

The sensitivity of Zaria strains of Plasmodium falciparum to chloroquine, mefloquine, quinine and sulphadoxine/pyrimethamine was investigated 5 years after the appearance of in vivo/in vitro chloroquine resistance in urban Zaria. Infections in 36/43 children (83.7%) treated with chloroquine were sensitive while those in 7 (16.3%) were resistant. 8/13 isolates cultured (61.5%) were sensitive in vitro to chloroquine and 5 (38.5%) were resistant. Of the cultured isolates, 13/13 (100%), 12/13 (92.3%) and 5/7 (71.4%) showed mefloquine, quinine and sulphadoxine/pyrimethamine sensitivity, respectively. The results confirmed chloroquine and sulphadoxine/pyrimethamine resistance in urban Zaria and revealed emerging quinine resistance. Resistance to chloroquine and sulphadoxine/pyrimethamine is at RI level and chloroquine should continue to be the first-line drug for the treatment and prevention of P. falciparum infection in the Zaria area of northern Nigeria. We suggest that, while quinine serves as second-line drug, mefloquine should be reserved for infections resistant to chloroquine, quinine and sulphadoxine/pyrimethamine.

Analgesic effect of Irvingia gabonensis stem bark extract.

Irvingia gabonensis is used medicinally in most parts of tropical Africa for the treatment of a number of ailments. In West Africa the Mende tribe of Sierra Leone uses the stem bark to relieve pain. In order to establish a pharmacological rationale for the traditional use of this plant as a remedy for pain, the water and ethanol extracts of the powdered stem bark were screened for analgesic activity and compared with standard analgesic drugs. The water extract and morphine protected the mice from heat-induced pain. In contrast, the ethanol extract and metamizole sodium showed very low level of analgesic activity in this test. However, using tail pressure as a source of pain, the water and ethanol extracts, metamizole sodium and morphine offered protection to the mice against pain stimuli. Morphine and the water extract were more potent as analgesic agents in heat than non-heat pain test. The analgesic effects of the water extract and morphine were blocked by a non-selective opioid receptor antagonist, naloxone in both tests, whereas the analgesic effects of the ethanol extract and metamizole sodium were not antagonized by the same dose of the opioid antagonist. The data presented in this study suggest that the active principle(s) in the water extract has analgesic profile similar to that of the narcotic analgesic and the ethanol extract might contain compound(s) that behave like non-narcotic analgesic agent. These findings provide for the first time the pharmacological basis for the folkloric use of Irvingia gabonensis in the relief of pain.

Propranolol pharmacokinetics during the menstrual cycle.

The pharmacokinetics of propranolol during menstruation and in the mid menstrual cycle have been studied in nine young women taking a single 80 mg tablet on each occasion. There were wide between-individual differences in the serum concentration at any given time (4-5 fold at peak concentrations) but the serum concentration time curves within individuals showed only mild variations. The differences between the average pharmacokinetic parameter estimates for the group did not differ significantly between the two periods of study.

Acute toxicity studies with Jatropha curcas L.

The seeds of Jatropha curcas L. ingested accidentally by two children aged 3 and 5 years led to a clinical syndrome of restlessness, severe vomiting and dehydration. A systematic study of the seeds indicated that they produced toxic effects in mice. Macroscopic anal haemorrhage and death occurred when the seeds were administered with the feed. Post-mortem examination revealed infarction of various parts of the gastrointestinal tract with congested vessels. Sodium chloride solution (150 mmol/l: saline) extract of the dried seed administered intraperitoneally into mice caused death in doses as low as 1 mg/kg. Post-mortem studies in this case showed widespread haemorrhages involving the colon, lungs as well as infarction of the liver. Larger intraperitoneal doses (greater than 30 mg/kg) were lethal rapidly but not associated with gross gastrointestinal haemorrhage.

Influence of dosing interval and in-patient versus out-patient status on incidence of side-effects of niridazole.

The side-effects of niridazole used for urinary schistosomiasis were studied prospectively over a 3-month period in male patients receiving the standard dose of 25 mg day-1 kg-1 for 7 days. Side-effects were detected in 80% of in-patients but only in 33% of out-patients. The range of side-effects was greater in in-patients taking their daily doses in two portions than in those taking theirs in three. Cure rates and degree of schistosoma egg suppression were significantly lower in out-patients suggesting that compliance with treatment was poorer.