Pharmacological evidence favouring the use of Nauclea latifolia in malaria ethnopharmacy: effects against nociception, inflammation, and pyrexia in rats and mice.

AIM OF THE STUDY: Nauclea latifolia Smith is used traditionally in the treatment of uncomplicated malaria and painful conditions among its several other applications. The objective of this study is to investigate the pharmacological activities of the plant relevant to the symptomatic treatment of malaria fever and other painful conditions as an initial step towards developing an effective therapy for the symptomatic management of malaria fever and relief of other painful conditions. MATERIALS AND METHODS: Various concentrations of the aqueous extract of the root bark of this plant were evaluated for its anti-nociceptive, anti-inflammatory and anti-pyretic activities in mice and rats. Investigation of the anti-nociceptive activities was performed using the acetic acid-induced abdominal constriction and hot-plate tests in mice and formalin-induced pain test in rats, as models of nociception. The extract was also investigated for its effect against inflammation induced by egg-albumin and pyrexia induced by yeast in rats. RESULTS: Our data showed that the aqueous extract of Nauclea latifolia root bark (50-200mg/kg p.o.) significantly (P<0.05) attenuated writhing episodes induced by acetic acid and increased the threshold for pain perception in the hot-plate test in mice, dose-dependently. The product also remarkably decreased both the acute and delayed phases of formalin-induced pain in rats and also caused a significant reduction in both yeast-induced pyrexia and egg-albumin-induced oedema in rats. These effects were produced in a dose-dependent manner. CONCLUSION: The results suggest the presence of biologically active principles in the extract with anti-nociceptive, anti-inflammatory and anti-pyretic activities that justifies its use in malaria ethnopharmacy and subsequent development for clinical application.

Ocular morbidity from sickle cell disease in a Nigerian cohort.

UNLABELLED: Sickle cell Retinopathy is increasingly being recognised as a cause of significant ocular morbidity and blindness in Africa south of the Sahara. This study looked for retinopathy in a cohort of 90 Nigerians with Sickle Cell Disease (SCD). METHOD: The cohort consisted of black Nigerians from the Hausa-Fulani, Ibo and Yoruba, as well as other minority ethnic groups resident in the Federal Capital Territory aged between 5-36 yr. 88 patients were SS and only 2 SC. RESULTS: SCD related posterior lesions were seen in 22 patients (24%). Of these, 19 cases (21%) had Non Proliferative Sickle Retinopathy (NPSR) while 5 (5.6%) had Proliferative Sickle Retinopathy (PSR) in various stages of development, and 2 had both PSR and NPSR. Patients with PSR are at risk of blindness from vitreous haemorrhage and tractional retinal detachment. A 14-year-old male with arterio-venous anastomosis was the youngest with PSR while the most advanced PSR lesion was a sea fan in a 25-year-old female. CONCLUSIONS: standard treatment consisting of photocoagulation and/or vitrectomy is not available in many eye centres in sub-Saharan Africa and steps need to be taken to improve this situation. The role of anti-sickling remedies, if any, is the subject of ongoing investigations. Our findings with NIPRISAN, a phytomedicinal preparation currently undergoing trials, will be reported subsequently.

Anti-diarrhoeal and ulcer-protective effects of the aqueous root extract of Guiera senegalensis in rodents.

The anti-diarrhoeal and ulcer-protective properties of the aqueous root extract of Guiera senegalensis, a popular herbal traditional medicine in Nigeria were investigated in rats and mice. Acute toxicity studies were also carried out. The intestinal transit in mice was significantly (P < 0.05) reduced and gastric emptying delayed. One hundred and Two hundred milligrams per kilogram (p.o.) of the extract elicited a greater anti-motility activity than 0.1 mg/kg of atropine. The extract exhibited ulcer-protective properties against ethanol-induced ulceration in rats with maximal anti-ulcer activity recorded at 100 mg/kg. Guiera senegalensis also exerted significant anti-enteropooling effects causing a dose-related inhibitory effect on castor oil-induced enteropooling in rats. A profound anti-diarrhoeal activity was observed when Guiera senegalensis was tested in diarrhoeic mice. The frequency of defaecation as well as the wetness of the faecal droppings was significantly reduced. Furthermore, the extract produced 100% inhibition of castor oil-induced diarrhoea in mice. The oral LD50 values obtained were > 5000 mg/kg in both mice and rats. The results support the folkloric applications of Guiera senegalensis for the treatment of diarrhoea and ulcer in Nigerian herbal traditional medicine.

Neuropharmacological effects of the aqueous extract of Nauclea latifolia root bark in rats and mice.

The present study evaluated the neuropharmacological effects of the aqueous extract of Nauclea latifolia root bark in rodents. Effects on the spontaneous motor activity (SMA), exploratory behaviour, pentobarbital sleeping time, apomorphine-induced stereotypic behaviour and motor coordination (rota-rod performance) were investigated. The extract (50-200 mg/kg p.o.) significantly (P<0.05) decreased the SMA and exploratory behaviour in mice and prolonged pentobarbital sleeping time in rats dose-dependently. The extract also remarkably attenuated the intensity of apomorphine-induced stereotypy dose-dependently in mice, but had no effect on motor coordination as determined by the performance on rota-rod. These results indicate the presence of psychoactive substances in the aqueous extract of the root bark of Nauclea latifolia.

Postsynaptic dopamine (D(2))-mediated behavioural effects of high acute doses of artemisinin in rodents.

Artemisinin or qinghaosu is the active principle of quinghao (Artemisia annua L.) developed from Chinese traditional medicine, which is now widely used around the world against falciparum malaria. Behavioural effects of high acute doses of artemisinin were studied on spontaneous motor activity (SMA), exploratory behavior, apomorphine-induced stereotype behavior and pentobarbital sleeping time in mice and rats in order to provide additional evidence on its safety profile on the central nervous system (CNS). Effects of the drug on bromocriptine-induced hyperactivity in short term reserpinised mice were also evaluated. Intraperitoneal (i.p.) injection of artemisinin at doses of 50 and 100mg/kg, significantly (P<0.05) reduced the SMA in mice, prolonged the pentobarbital sleeping time in rats, and attenuated the apomorphine-induced stereotypy in mice. Mice pretreated with reserpine, showed a significant decrease in locomotor activity compared to the saline-treated group. Bromocriptine, a D(2) receptor agonist, induced locomotor activity in mice pretreated with reserpine which was attenuated by artemisinin. The results suggest that artemisinin possesses sedative property, which may be mediated via postsynaptic dopamine (D(2)) receptor in the CNS.

Smooth muscle contraction induced by Indigofera dendroides leaf extracts may involve calcium mobilization via potential sensitive channels.

The contractile effects of the aqueous extract of the leaves of Indigofera dendroides (ID) were studied on the gastrointestinal motility in mice and isolated smooth muscle preparations obtained from rats and guinea pigs. The contractile effects of 10(-6) M acetylcholine, 80 mM KCl and 1.6 mg/ml ID were measured on the rat ileal smooth muscle exposed to calcium-free buffer or physiological solution, to determine the calcium pools mobilized by extract for activation of contraction. Acute toxicity test (LD(50)) was also carried out in mice. The result showed that ID (0.05-3.2 mg/ml) produced a concentration-dependent contraction of the guinea pig and rat ileum. These responses were not blocked by mepyramine (2.49 x 10(-9) M), verapamil (8.14 x 10(-9) M), or pirenzepine (4.7 x 10(-7) M), but were blocked completely by atropine (2.92 x 10(-9) M). A significant increase in propulsion of gastrointestinal motility was observed. Acetylcholine, KCl and ID produced contractions in Ca(2+) free media. The phasic components of the contractile responses to Ach as well as the tonic component of K(+) and ID-induced contractions were relatively resistant to short periods of calcium-free exposure. Ach, K(+) and ID still caused contractions in the presence of verapamil. The data revealed that ID-induced contractions were not mediated by histaminergic receptors, calcium channels, M1 muscarinic receptors. It also suggests that Ach mobilize Ca from some tightly bound or intracellular pool, whereas high K(+) and ID may mobilize Ca from some superficial or loosely-bound pool.

Effect of the aqueous extract of Chrysanthellum indicum on calcium mobilization and activation of rat portal vein.

The effects of the aqueous extract of Chrysanthellum indicum (CI) on calcium activation and mobilization were studied using the rat portal vein. The extract caused a concentration-dependent contraction of the portal vein. KCl (80 mM), norepinephrine (NA, 10(-6)M) and CI (4 mg/ml) evoked sustained contraction of the portal vein. In Ca-free medium (with EGTA) the contractions evoked by these agents were reduced significantly. The times-to-peak of KCl, NA and CI were similar -in normal PSS, but in Ca-free medium the times-to-peak for KCl and CI were greatly increased. The contractions induced by CI were not inhibited by chlorpropamide and prazosin, but were blocked by verapamil. The data obtained suggest that the aqueous extract of CI utilizes extracellular calcium pools to bring about contractile response and this effect might be mediated through the activation of potential-sensitive channels.

Central inhibitory activity of the aqueous extract of Crinum giganteum.

The aqueous extract of Crinum giganteum given intraperitoneally at doses of 6.25, 12.5 and 25 mg/kg in rats prolonged the duration of pentobarbital sleeping time and in mice reduced spontaneous motor activity, decreased the exploratory activity and attenuated amphetamine-induced stereotype behavior. The intraperitoneal and oral preliminary LD(50) in mice were found to be 627 and 1468 mg/kg, respectively. The data obtained suggest that the aqueous extract of C. giganteum contains some biologically active principles with sedative activity.

Central nervous system activity of the methanol extract of Ficus platyphylla stem bark.

The central nervous system (CNS) activity of the methanolic extract of Ficus platyphylla stem bark was studied on locomotor activity, pentobarbital sleeping time, exploratory behaviour, amphetamine-induced hyperactivity, apomorphine-induced stereotypy, active-avoidance and performance on tread mills (rota-rod), using mice and rats. The results revealed that the extract significantly reduced the locomotor and exploratory activities in mice, prolonged pentobarbital sleeping time in rats, attenuated amphetamine-induced hyperactivity and apomorphine-induced stereotypy in mice, dose-dependently. The extract significantly suppressed the active-avoidance response in rats, with no significant effect on motor co-ordination as determined by the performance on rota-rod. The results suggest that the extract may possess sedative principles with potential neuroleptic properties.

A multicentre study to determine the efficacy and tolerability of a combination of nelfinavir (VIRACEPT), zalcitabine (HIVID) and zidovudine in the treatment of HIV infected Nigerian patients.

Summary Forty (40) HIV positive patients with CD4 cell counts between 100 - 500 cellh/mm3 were recruited from 8 different centres in Nigeria including a research centre and specialist and teaching hospitaLs They were enrolled into an open, non-comparative study of a triple combination regimen containing the Protease Inhibitor (PI), Nelfinavir and two Reverse Transcriptase Inhibitors (RTIs), Zakitabine (Hivid) and Zidovudine for a period of 24 weeks. Thirty-one (31) patients completed the study. Nine (9) patients withdrew from the study. Two of these because of Adverse Events (AE), 2 others because they developed tuberculosis and had to withdraw because of rifampicin therapy. The remaining five (5), withdrew voluntarily. Efficacy of the PI containing triple regimen was evaluated using viral load and absolute CD4 changes, weight gain and clinical response during the course of the triaL Twenty-two (22) patients had plasma viral loads measured at the beginning and at the end of the trial (24 weeks). Seventeen (17) out of the 22 patients (77%), experienced a significant reduction in their plasma viral loads (p<0.05 There was 1 log reduction in plasma viral load in 6 patients (25%), 2 log in 4 patients (17%). In 2 patients (8%), plasma viral load was reduced below the level of detection. The viral load increased over the treatment period in five patients (21%). Similarly 22 out of the 26 patients (85%) experienced increase in the level of their CD4 lymphocyte counts at the end of the study. The average CD4 counts of all 26 patients rose from 272.94 +/- 137.71/dl to 414 +/- 243.71/ul over 24 weeks (p<0.05). There was monthly rise of 27 CD4 cells/microl. Four (4) patients (15%) had a fall in their CD4 lymphocyte counts. Twenty (20) out of the 26 patients (77%), who completed the study were observed to have weight gains ranging from 1.5 to 31 kilograms over the 24 week study period. In 4 patients, there was no weight gain during the study period. Two patients (5%) were withdrawn due to adverse events from the viracept combination. One of these was because of life threatening diarrhoea while the other patient had severe peripheral neuropathy and severe weakness in the lower limbs. Eight (8) other patients had diarrhoea but not severe enough to stop them from continuing with the triaL Other adverse events seen include anaemia (1 patient), pancytopenia (1 patient), and transient elevation of serum urea and creatinine (1 patient). None of these adverse events was severe enough to warrant withdrawal from therapy. The study has therefore demonstrated the significant efficacy and tolerability of (Nelfinavir/Zalcitabine/ Zidovudine combination in suppressing viral replication, increasing the CD4 cell counts and improving the quality of life in Nigeria patients with HIV.

Antinociceptive and smooth muscle contracting activities of the methanolic extract of Cassia tora leaf.

The leaves of Cassia tora Linn. (Family: Caesalpiniaceae) were soxhlet extracted with methanol. The spasmogenic effects of the extract were evaluated on guinea pig ileum, rabbit jejunum and mice intestinal transit. Antinociceptive activity of the extract was also evaluated in the mice. The LD(50) values of the extract in mice were >2000 mg/kg i.p. and p.o. The extract contracted smooth muscles of guinea pig ileum and rabbit jejunum in a concentration-dependent manner. Atropine reversibly blocked this activity. Mepyramine also reduced the contractile amplitude due to the extract in a concentration-dependent manner. The extract increased intestinal transit in mice dose dependently. C. tora extract significantly (P<0.05) reduced the number of acetic acid induced abdominal constrictions in mice and the effect was comparable to that of aspirin (150 mg/kg i.p.). The extract also significantly (P<0.05) reduced the nociceptive response of mice to increased force (g). The effects were dose-dependent. The studies suggest that the use of C. tora, traditionally, as a purgative and in the treatment of other ailments is justifiable.

Molecular surveillance of HIV-1 field strains in Nigeria in preparation for vaccine trials.

We conducted a national molecular epidemiologic survey of HIV-1 strains in Nigeria to determine the most prevalent subtype(s) for use in developing candidate vaccines. A total of 230 HIV-1-positive blood samples collected from 34 of the 36 Nigerian states were analyzed by our modified env gp41-based heteroduplex mobility assay (HMA) and/or gp41 sequencing and analysis. Overall, 103 (44.8%) were subtype A, 125 (54.3%) were subtype G, one (0.4%) was subtype C, and one (0.4%) was subtype J, and one (0.4%) was unclassifiable. To further characterize Nigerian viruses to aid in strain selection for candidate vaccines, one gp41 subtype G and five gp41 subtype A strains were selected for full envelope sequencing. The one subtype G sequence had consistent phylogenies throughout gp160, using programs to detect recombination. However, all five sequences that were primarily subtype A in gp41 were found to be recombinant viruses. Two of the five (40%) were A/G/J mosaics with common breakpoints. The remaining three gp160 recombinants all had their own unique break points: two A/? and one A/?/G, however, all five had the majority of their mosaic breakpoints occurring in gp41. None of the five were consistent with the circulating recombinant form (CRF)02_AG strain previously reported to be prevalent in West Africa. In conclusion, we showed a clear dominance and widespread distribution of gp41 subtypes A and G in fairly equal proportions, suggesting that vaccines designed for use in this geographic locale should incorporate the gene(s) of both subtypes. However, appreciating the magnitude of diversity of HIV-1 strains in Nigeria may require sequencing and analysis of longer gene regions for the identification of prevalent or emerging CRFs.

Sedative effects of the methanolic leaf extract of Newbouldia laevis in mice and rats.

The effect of the methanolic extract of Newbouldia laevis seem on the central nervous system of rats and mice was investigated. The extract was tested on spontaneous motor activity, exploratory behaviour, apomorphine induced climbing behaviour in mice and pentobarbital induced hypnosis in rats. The extract caused considerable reductions of exploratory activity, spontaneous motor activity and prolonged pentobarbitone-induced hypnosis in rats. It was also found to attenuate apomorphine climbing in mice. The results suggest that the methanolic extract of Newbouldia laevis may contain principles that have sedative properties.

Effect of Zizyphus spina-christi Willd aqueous extract on the central nervous system in mice.

The effects of the aqueous extract of Zizypus spina-christi Willd root bark against exploratory behaviour, spontaneous motor activity (SMA), motor coordination (Rota-rod performance) and pentobarbital-induced hypnosis were investigated in mice. The extract induced a significant (P<0.05) dose-dependent reduction in exploratory behaviour and SMA when administered orally. It also prolonged pentobarbital sleeping time but failed to inhibit motor coordination (rota-rod performance) in the experimental mice. These results suggest that the extract contained some constituents that depress the central nervous system, which may not be due to neuromuscular blockade.

Effect of the aqueous extract of African mistletoe, Tapinanthus sessilifolius (P. Beauv) van Tiegh leaf on gastrointestinal muscle activity.

Effects of the aqueous extract of T. sessilifolius on the gastrointestinal muscle were investigated on smooth muscle preparations isolated from rabbit jejunum, guinea pig ileum and on gastrointestinal transit in mice. Elemental analysis of the extract was also carried out. The aqueous extract of T. sessilifolius evoked a concentration dependent contraction of the rabbit jejunum and guinea pig ileum. The contractions evoked by the extract were not attenuated either by atropine or mepyramine, but they were completely blocked by verapamil. The elemental analysis revealed the presence of Mg, Zn, Fe, Cu, and very high concentration of Ca. The intraperitoneal LD50 in mice was found to be 1500 mg/kg. The aqueous extract of T. sessilifoliius possesses active components that may be mediating the observed biological activity through calcium mobilization.

Behavioral effects of the aqueous extract of Guiera senegalensis in mice and rats.

Behavioral effects of the aqueous extract of Guiera senegalensis on the central nervous system of mice and rats were investigated. Spontaneous motor activity, pentobarbital sleeping time, amphetamine-stereotyped behavior, exploratory activity and performance on treadmills (rota-rod) were evaluated. The results revealed that the aqueous extract of G. senegalensis reduced spontaneous motor activity in mice, prolonged the duration of pentobarbital sleeping time in rats and attenuated amphetamine-induced stereotype behavior in rats. The extract also decreased exploratory activity in mice and had no observable effects on motor coordination (rota-rod) at the doses tested. The results suggested that the crude aqueous extract of G. senegalensis possesses some biologically active principles that are sedative in nature.

Effect of niprisan on single oral dose pharmacokinetics of paracetamol in rats.

The single oral dose pharmacokinetics of paracetamol was studied alone and after coadministration with NIPRISAN In rats. Paracetamol concentrations were measured in rat plasma using UV-spectrophotometer and the data were fitted into an open two-compartment pharmacokinetic model using the computer program (STATIS Version 3.0). Results indicated no significant difference in the absorption of paracetamol between study and control groups but a significant reduction (p < 0.05) at some sampling time as the dose of NIPRISAN was increased double-fold. The pharmacokinetic parameters showed only 1.51 and 7.19% reduction in AUC(0-infinity) and Cmax respectively for paracetamol (20 mg/kg) + NIPRISAN (500 mg/kg). It was thus concluded that the gastric presence of NIPRISAN did not significantly reduce the absorption of paracetamol in rats.

Anti-inflammatory, analgesic and anti-lymphocytic activities of the aqueous extract of Crinum giganteum.

The anti-inflammatory, anti-lymphocytic and analgesic properties of Crinum giganteum, a popular herb used for the management of asthma and other respiratory disorders was investigated in rats and mice. The extract dose-dependently produced significant (P<0.05) inhibition of formalin induced pain in rats. It also demonstrated significant (P<0.01) inhibition of abdominal constriction induced with 0.75% v/v acetic acid in mice. On the cotton pellet induced granulomatous tissue formation in rats, the extract significantly (P<0.05) decreased the weight. However, no significant inhibition was observed in the egg albumin-induced inflammation in rats. Oral administration of this extract in rats for 14 days significantly affected (P<0.05) the total leukocyte count and the overall percentage lymphocytes. The intraperitoneal and per oral LD(50) were 627+/-5.8mg/kg and 1486+/-18.9 mg/kg in mice and 520+/-10.2mg/kg and 1023+/-4.3 mg/kg in rats, respectively. Preliminary phytochemical analysis of the extract indicates the presence of tannins. These results therefore indicate that C. giganteum bulb contains biologically active principles, which have potentials for the treatment of inflammatory processes.

Neuropharmacological effect of the aqueous extract of Sphaeranthus senegalensis in mice.

Effects of the aqueous extract of Sphaeranthus senegalensis Vaill. (Family: Compositae) were studied on spontaneous motor activity, exploratory behaviour, rota-rod performance and pentobarbital sleeping time in mice. Preliminary phytochemical evaluation and acute toxicity (LD(50)) values were also studied. The extract (50 and 100 mg/kg p.o.) produced reduction in spontaneous motor activity, exploratory behaviour and motor coordination and prolonged pentobarbital sleeping time. Glycosides, saponins and tannins were shown to be present in the extract. The i.p. LD(50) in mice was 2735.61 and 5000 mg/kg orally. The results suggest that the aqueous extract of S. senegalensis contains some active principles, which may be sedative in nature.

Antidiarrhoeal activity of the aqueous extract of Terminalia avicennoides roots.

The antidiarrhoeal effects of the aqueous root extract of Terminalia avicennoides were evaluated in rodents. Studies were carried out on the isolated rabbit jejunum, gastrointestinal motility in vivo and on castor oil-induced diarrhoea in mice. The results revealed that the extract exhibited a concentration-dependent inhibition of the spontaneous pendular movement of the isolated rabbit jejunum and attenuated acetylcholine induced contractions. The extract (100, 200 and 400 mg/kg) also caused a dose-dependent decrease of gastrointestinal transit and markedly protected mice against castor oil-induced diarrhoea. The intraperitoneal LD(50) of the extract was found to be 871.4-917.4 mg/kg in mice (95% confidence). A preliminary phytochemical screening of the aqueous extract of T. avicennoides roots revealed the presence of tannins, saponins and flavonoids. The results obtained showed that the water extract of T. avicennoides roots may contain some biologically active principles that may be active against diarrhoea and this may be the basis for its use traditionally for gastrointestinal disorders.