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.

Psychopharmacological Properties of the Saponin Fraction of Ficus Platyphylla Stem Bark

The psychopharmacological effects of a saponin-rich fraction (SFG) obtained from crude methanolic extract of Ficus platyphylla stem bark were studied on spontaneous motor activity (SMA); pentobarbitalinduced sleep; motor coordination; amphetamine-induced hyperactivity and stereotyped behaviour; catalepsy; forced swim and tail suspension tests in rodents. SFG reduced SMA dose dependently; suggesting that it may contain psychoactive principles with sedative effects. The fraction shortened the onset and prolonged the duration of pentobarbital-induced sleep; which confirmed its sedative properties. The fraction diminished immobility time in forced swim and tail suspension tests; which is indicative of antidepressant properties. It attenuated amphetamine-induced hyperactivity and stereotyped behaviour; induced catalepsy and exacerbated haloperidol-induced catalepsy in rodents; but had no effect on motor coordination in the treadmill experiment at the doses tested. These effects were similar to those of classical neuroleptics and antidepressants. Our study provides scientific evidence of psychopharmacological effects of the saponin fraction of Ficus platyphylla stem bark and therefore supports further development of its psychoactive components as antipsychotics and antidepressants

Effect of Annona senegalensis rootbark extracts on Naja nigricotlis nigricotlis venom in rats.

Annona senegalensis Pers (family: Annonaceae) is used traditionally in Nigeria to treat victims of snakebite. The potency of the methanol extract of the root bark of the plant was tested against cobra (Naja nigricotlis nigricotlis Wetch) venom in rats. The extract was also tested on brine shrimp (Artemia saline Leach). The activity of the extract against the venom induced mortality, occurrence of toxic signs, activity on liver enzymes as well as its ability to reverse experimentally induced increase in body temperature were evaluated. Results indicated that the extract caused reduction in the induced hyperthermia and directly detoxified the snake venom used by 16-33%. It, however, failed to restore the biochemical functions (sGOT and sGPT) of the liver. The extract exhibited an LC(50) of 232.7 microg/ml in the brine shrimp test.

The efficacy of Sphaeranthus senegalensis Vaill extract against diarrhoea in rats.

The aqueous extract of Sphaeranthus senegalensis (Asteraceae) was investigated for anti-diarrhoeal activity in rats. Its effect on castor oil-induced diarrhoea and fluid accumulation and on gastrointestinal (charcoal meal) test was evaluated. Results showed that pre-treatment for 30 min with the extract at 50, 100 and 200 mg/kg, p.o. causes a dose-dependent protection against castor oil-induced diarrhoea and intraluminal fluid accumulation and inhibited gastrointestinal transit motility. These results suggest that the plant contain active constituents that may be useful against diarrhoea.

Is Berlina grandiflora (Leguminosae) toxic in rats?

The toxicity profile of the aqueous methanolic extract of Berlina grandiflora (BG) stem bark was studied in rats. The rats were administered graded doses (125-500 mg/kg p.o) of the extract daily for 21 days and the effects on body weight, organ weight, clinical signs, gross pathology, hematology, histology and serum biochemical parameters were measured. The relative weights of the heart, liver, kidneys and lungs of treated rats were unaffected but there were significant changes in the relative weights of the spleen and testes. The packed cell volume and hemoglobin concentrations were slightly reduced whereas total leucocytes counts were increased remarkably. Alkaline phosphatase and Creatine Kinase levels were reduced in all the groups but Glutamate oxaloacetate was significantly elevated. Total proteins and albumin levels remained normal. BG elicited a significant increase in gamma glutamyl transferase concentrations at 250 mg/kg. No significant changes occurred in urea, uric acid and BUN concentrations but calcium levels shot up remarkably. Histological findings did not reveal any treatment-related effects. The acute toxicity LD50 was estimated to be >2000 mg/kg but dose-related mortality rates of 16.7, 33.4 and 50% were observed during the sub-acute toxicity studies. These findings have once more highlighted the limitations of acute toxicity LD50 testing and suggest that BG may exert varied toxicological effects when administered orally in rats.

Antinociceptive profile of the methanolic extract of Neorautanenia mitis root in rats and mice.

The antinociceptive activity of the methanolic extract of Neorautenania mitis was studied in mice and rats. Five experimental models of nociception employed were: acetic acid-induced abdominal constriction and hot-plate test in mice, formalin-induced pain, analgesy-meter and Randall-Selitto tests in rats. The antinociceptive action of the extract was tested against naloxone in the hot-plate test in a bid to further elucidate probable mechanisms of antinociception. Results showed that the extract at doses of 5, 10 and 20 mg/kg body weight caused significant (P<0.05) dose-dependent antinociceptive activity in all the nociceptive models. Naloxone (2 mg/kg), significantly (P<0.05) antagonised the antinociceptive activity at the highest dose of the extract (20 mg). The study showed that the methanolic extract of Neorautanenia mitis possesses both peripherally and centrally mediated antinociceptive activity. The peripherally mediated action may be linked partly to lipoxygenases and/or cyclo-oxygenases, while the central anti-nociception is likely to be mediated via opioid receptors in the CNS.

Anti-nociceptive and anti-inflammatory activities of the methanolic extract of Parinari polyandra stem bark in rats and mice.

The methanolic extract of the stem bark of Parinari polyandra (family Rosaceae) was investigated for possible anti-nociceptive and anti-inflammatory effects in mice and rats. Three models were used to study the extracts effects on nociception which were the acetic acid-induced abdominal constriction test, hot-plate method (both in mice) and the formalin test in rats. The anti-inflammatory effects were investigated employing the albumin-induced hind-paw oedema in rats. Results of the study revealed the extract to have significant (P<0.05) anti-nociceptive effect at a dose of 200 mg/kg p.o. in mice and rats in all the models for anti-nociception while 100 mg/kg p.o. showed significant (P<0.05) effect in the acetic acid-induced abdominal constriction test and in phase I of the formalin test. The extract also exhibited anti-inflammatory effects which were found to be significant (P<0.05) at 200 mg/kg p.o. in the rats tested. Preliminary phytochemical screening of the extract showed the presence of flavonoids, tannins, and saponin glycoside. The results suggest the extract contains pharmacologically active principles. The result is in agreement with the local application of the plant in painful and inflammatory conditions.

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.

Anti-inflammatory and anti-nociceptive effects of Sphaeranthus senegalensis.

Sphaeranthus senegalensis Vaill (Asteraceae) is used in traditional medicine as a remedy for rheumatic pains and other ailments. The anti-inflammatory and anti-nociceptive activity of the aqueous extract of the whole shoot of the plant was evaluated in mice and rats. Activity of the extract against egg-albumin induced hind paw oedema was measured to evaluate the anti-inflammatory activity while the anti-nociceptive potency was evaluated using three painful stimuli viz acetic acid induced abdominal constriction and hot plate test in mice, and the formalin test in rats. Results indicated that the extract possess remarkable dose dependent anti-inflammatory activities in rats. The extract also showed anti-nociceptive activities against acetic acid induced writhing, formalin and the hot plate pain models. The effects were significant (P < 0.05) when compared with the saline control group. The results suggest the presence of a potent anti-inflammatory and anti-nociceptive principle in the extract, which support the folkloric use of the plant in relieving rheumatic pains.

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.

Neuropharmacological screening of Diospyros mespiliformis in mice.

The neuropharmacological activities of the aqueous extract of Diospyros mespiliformis stem bark were screened in mice. The extracts effect on pentobarbital-induced sleeping time, pentylenetetrazole induced seizure, spontaneous motor activity (SMA), exploratory behaviour, and rota-rod performance (motor coordination) were evaluated. The extract (100 and 200 mg/kg p.o.) produced a significant (P<0.05) prolongation of pentobarbital-induced sleeping time, and reduced the SMA and exploratory behaviour. The extract prolonged onset of the phases of seizure activity but did not protect mice against lethality induced by pentylenetetrazole. It also failed to affect the motor coordination test. These results suggest that the extract contained an agent with neuropharmacological activity that may be sedative in nature.

Pharmacological evidence favouring the folkloric use of Diospyros mespiliformis Hochst in the relief of pain and fever.

The methanol extract of Diospyros mespiliformis was evaluated for its claimed folkloric usage in the relief of pain and fever. Antipyretic, analgesic and anti-inflammatory effects of the extract were evaluated in rats and mice. Studies were carried out on yeast-induced pyrexia in rats, acetic acid-induced writhing in mice, formalin test and egg albumin-induced anti-inflammatory activity in rats. The extract (50 and 100 mg/kg i.p.) gave a potent antipyretic effect for 100 mg/kg and significant activity (P<0.05) against all the analgesic and anti-inflammatory models used. The LD(50) of the extract was estimated to be 513.80+/-33.92 mg/kg i.p. in mice. These results provide support for the use of the plant in relieving pain and fever.

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.

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.

Double-blind, placebo-controlled, randomised cross-over clinical trial of NIPRISAN in patients with Sickle Cell Disorder.

The study was undertaken to determine the safety and efficacy of NIPRISAN, a phytomedicine, developed for the management of patients with Sickle Cell Disorder (SCD). The study design is a placebo-controlled double blind cross-over trial. Eighty-two (82) patients with SCD were recruited and randomised into two groups. An initial 4 month pre-trial study was undertaken to determine the similarity of the groups. The main study was conducted over a twelve-month period with crossover at six months. Safety of the drug was assessed clinically and biochemically. NIPRISAN significantly (P < 0.01) reduced the frequency of SCD crisis associated with severe pains. Acute toxicity to the liver assessed by the activities of liver enzymes, indicate that NIPRISAN is safe. Renal function assessed by the serum levels of creatinine and blood urea nitrogen remained normal. Both the clinical and laboratory results of the present phase IIB (pivot) clinical study suggest that NIPRISAN is a safe and efficacious phytomedicine for the management of patients with Sickle Cell Disorder.

Pharmacological effects of the aqueous extract of Neorautanenia mitis in rodents.

The pharmacological effects of the aqueous extract of Neorautanenia mitis (family Papilonaceae) were studied in rodents. Investigations were carried out on acetic acid-induced writhing (pain) in mice and hind paw oedema in rats. The effects of the extract were also studied on the isolated non-pregnant rat uterus and rabbit jejunum. Results showed the extract to possess significant (P<0.05) dose-dependent anti-nociceptive activity between 12.5 and 50.0 mg/kg p.o. in mice and slight anti-inflammatory activity at 25 and 50 mg/kg p.o. in rats. The extract also produced a concentration-dependent inhibition of the normal rhythmic contraction of the isolated non-pregnant rat uterus. It was found to inhibit oxytocin-induced as well as acetylcholine-induced contractions in the rat uterus. The extract also exhibited concentration-dependent inhibition of spontaneous contractions of the rabbit jejunum. Preliminary phytochemical analysis of the extract revealed the presence of saponin glycosides, flavonoids, tannins and alkaloids. The extract had an intraperitoneal (i.p.) LD(50) of 282.84+/-3.2 mg/kg in mice. These data corroborate the traditional use of this plant in the treatment of dysmenorrhea.

The pharmacological effects of an aqueous extract from Acacia nilotica seeds.

An aqueous extract of the seed of Acacia nilotica was investigated for its pharmacological profile. On the isolated guinea-pig ileum, the extract displayed sustained dose-related contractile activity. The contractions which were reduced by hexamethonium, promethazine or atropine were completely abolished by nifedipine. The intravenous (i.v.) administration of the extract (11, 22, 44, 55 microg/kg) to anaesthetized cats produced a dose-related significant elevation of blood pressure. The mechanisms of the spasmogenic and vasoconstrictor actions of the extract have not been determined, however, the results suggest the involvement of calcium.

Antihypertensive effect of roselle (Hibiscus sabdariffa) calyx infusion in spontaneously hypertensive rats and a comparison of its toxicity with that in Wistar rats.

The LD(50) of roselle calyx extract and its effect on blood pressure were determined. The LD(50) was found to be above 5000 mg kg(-1). Roselle calyx infusion was found to lower significantly (p<0.05) both systolic and diastolic pressure in spontaneously hypertensive and normotensive Wistar-Kyoto rats at tested doses of 500 and 1000 mg kg(-1) body weight. The reduction in blood pressure in both groups was positively correlated with weight. Continuous consumption of the infusion at 1000 mg kg(-1) was discovered to lead to sudden death in spontaneously hypertensive rats but not in Wistar-Kyoto rats. Water intake was not significantly different (p>0.05) in the control groups of the two strains of rats used, neither was there a significant difference in their urine output. The water intake in the treated spontaneously hypertensive and normotensive rats was not different from the corresponding control groups. However the urine output of the treated spontaneously hypertensive rats was significantly higher. A significant decrease in serum creatinine, cholesterol, and glucose in the treated rats compared with the control as well as a significant increase in serum uric acid was observed. The serum proteins (albumin and total protein) in the treated rats when compared with the control groups was not changed significantly.

Evaluation of Nigerian traditional medicines: II. Effects of some Nigerian folk remedies on peptic ulcer.

Antiulcer activity of four medicinal plants, Diodia sarmentosa (whole plant), Cassia nigricans (leaves), Ficus exasperata (leaves) and Synclisia scabrida (leaves), which are commonly used by the Nigerian traditional healers for the treatment of peptic ulcer were investigated. Acute toxicity tests were also carried out. The results revealed that the four extracts possess significant anti-ulcerogenic properties in a dose-dependent way. They protected rats from aspirin-induced ulcerogenesis, delayed intestinal transit, increased the pH, and decreased both the volume and acidity of gastric secretion. These results correlate with local use of the plants.

Evaluation of Nigerian traditional medicine: effects of Gakani, a herbal anti-asthmatic drug.

The anti-asthmatic potential of Gakani, a popular herbal drug in Nigeria was investigated. The LD50 values of the freeze-dried aqueous extract in mice and rats were 20.9 +/- 2.4 mg/kg and 18.6 +/- 4 mg/kg, respectively. The extract unsurmountably blocked the effects of histamine and isoprenaline on the guinea pig tracheaL chain. It produced initial dose-related contractions of the isolated guinea pig ileum and rat stomach strip, which was followed by persistent autoinhibition and inhibition of histamine- and 5-hydroxytryptamine (5-HT)-induced responses of the two preparations, respectively. The extract had good anti-inflammatory effect in rats, causing a dose-related inhibition of the increase in the paw circumference (acute inflammation) induced by subplantar injection of fresh egg albumin. These results highlight the anti-asthmatic and toxic potential of this preparation and the need for a systemic approach in the study of traditional medicines.