Acute and sub-acute toxicity studies of the methanol extract of the leaves of Paullinia pinnata (Linn.) in Wistar albino mice and rats.

BACKGROUND: The aim of this study was to investigate the toxicological effects of the leaves of Paullinia pinnata Linn.(PP) in rodents using Wistar albino mice and rats as experimental models. METHODOLOGY: Acute toxicity study of the methanol extract of PP was carried out in Wistar strain albino mice using varying doses of the extract at 100, 200, 400, 800, 1600, 3200, 6400, and 10,000 mg/kg body weight. These doses were administered orally to male Wistar albino mice with the exception of the control group and observed for morbidity and mortality after Day 1, Day 7 and Day 14. Sub-acute toxicity study was conducted in male Wistar albino rats with varying doses of 50, 100, 200, 400 and 800 mg/kg body weight. These doses were administered orally once daily at 24 hour intervals for 28 days and the vehicle (physiological saline and Tween 80 (70:30 v/v)) was administered to the control groups in the experiments. Biochemical analyses were carried out on the plasma while pathological changes in the kidneys, liver and lungs were examined histologically. RESULTS: In the acute toxicity study, the mice did not show any form of morbidity or mortality. For the sub acute toxicity study, plasma levels of alkaline phosphatase (ALP), aspartate aminotransferase (AST), total cholesterol and the triglycerides were significantly elevated (p < 0.05) at the 400 mg/kg body weight dosage. Elevated levels of plasma ALP were also observed at 800 mg/kg body weight. The histopathological study showed that the lungs exhibited dose -dependent lymphocytic infiltrations and the pattern of occurrence of lesions observed in the liver was at a frequency of one rat per group at the 400 and 800 mg/kg body weight doses. CONCLUSION: The methanol leaf extract of Paullinia pinnata (Linn.) is well tolerated when orally administered at a dose of 200 mg/kg body weight but toxic at higher doses.

COMPARATIVE ASSESSMENT OF TOTAL PHENOLIC CONTENT IN SELECTED MEDICINAL PLANTS.

This study was to compare the total phenolic (TP) content in extracts from eleven plant materials collected at different geographical locations in Kenya, Nigeria, and USA. These plants have been selected because the majority of them are highly pigmented, from yellow to purple, and would therefore have economic value in industries for producing antioxidants and surfactants. Two of them were collected from the industrial and domestic waste outlets. Each analysis was achieved using the Folin-Ciocalteau technique. The order of decreasing phenolic acid content as gallic acid concentration (mg/g dry weight) was Prunus africana (55.14) > Acacia tortilis (42.11) > Khaya grandifoliola (17.54) > Curcuma longa (17.23) > Vernonia amygdalina (14.9)> Russelia equisetiformis (14.03) > Calendula officinalis (7.96) >Phragmites australis (control) (7.09) > Rauwolfia vomitoria (6.69) > Phragmites australis (industrial) (6.21) > Cnidoscolus aconitifolius (5.6). The TP contents of Spartina alterniflora species were below the detection limit.

Effect of Cnidoscolus aconitifolius leaf extract on the blood glucose and insulin levels of inbred type 2 diabetic mice.

The effects of Cnidoscolus aconitifolius (CA) leaf extract and chlorpropamide on blood glucose and insulin levels in the inbred type 2 diabetic mice are reported. After treatment with CA, the glucose levels were measured at 0 and 2-hour intervals in experimental groups and controls. Group I received no treatment and served as control; Group II was the reference and it received chlorpropamide; Groups I-III were moderately diabetic, 100-300 mg/dL blood glucose levels while Group IV were severely diabetic (> 300 mg/dL). Groups III and IV received CA and served as test groups. There was no significant difference between the blood glucose levels at 0 and 2 hours for the control group, (P>0.23) but there were statistically significant differences for Group II (P<0.0002); Group III (P<0.002) and Group IV (P<0.0001). For moderately diabetic mice, CA and chlorpropamide decreased the glucose levels by 25.6% and 16.3% respectively while for the severely diabetic mice CA decreased the blood glucose by 43.7%. It is proposed that CA has an insulinogenic property that possibly stimulated dormant beta-cells to secrete insulin. The histopathology of several organs in the treated animals was found to differ from the expected. The islets of Langerhans for example were found to be preserved in the time frame examined. Also the liver and kidney were found to display milder pathology in the treated groups.

Central nervous system depressant activity of Russelia equisetiformis.

The central nervous system depressant activity of the crude methanol extract (REC) and fractions (RE1, RE2, and RE3) of Russelia equisetiformis were evaluated in mice using the following models: amphetamine-induced stereotypy, picrotoxin-induced convulsion and phenobarbitone sleeping time. At 200-400 mg/kg, REC significantly increased phenobarbitone-sleeping time [P < 0.05] in a dose- dependent manner and also reduced the sleep latency significantly [P < 0.05]. The fractions, at doses 1.5 mg/kg for RE1 and 20 mg/kg for RE2 and RE3 also significantly prolonged Phenobarbitone sleeping time and sleep latency [P < 0.05]. Picrotoxin-induced convulsion was not prevented by 100-400 mg/kg of REC but this dose range significantly prolonged seizure latency. A significant reduction [P < 0.05] in amphetamine-induced stereotype behavior was observed with 200 mg/kg REC, but there was no protection against amphetamine-induced mortality. The results of this study suggest that Russelia equisetiformis methanol extract possesses central nervous system depressant activities.

Evaluation of the anti-inflammatory and analgesic properties of the extract of Russelia equisetiformis (Schlecht & Cham) Scrophulariacae.

A methanolic extract of Russelia equisetiformis whole plant was studied for anti-inflammatory and analgesic activities in rats and mice using carrageenan-induced rat paw oedema, acetic-acid-induced writhing and tail-flick test. The extract, at 10, 20 and 40 mg/kg, significantly (P <0.05) inhibited carrageenan-induced oedema in rats. Abdominal constriction induced by acetic acid was also inhibited by the extract, within the same dose range. The extract at the same dose also prolonged the latency period in the tail-flick response test, which was reverted by naloxone. The results suggested that the extract possesses potential anti-inflammatory and analgesic properties.

Evaluation of the anti-inflammatory and analgesic properties of Chasmanthera dependens leaf methanol extract.

A methanol extract of the dried leaves of Chasmanthera dependens was investigated for anti-inflammatory and analgesic activities. The extract (100--400 mg/kg, p.o.) produced dose-related inhibition of carrageenan-induced paw oedema and cotton pellet-induced granuloma in rats. Furthermore, an inhibition in the leakage of Evan's blue induced by acetic acid was observed in mice. At same doses, analgesic effect was also observed on writhing response induced by acetic acid as well as on the early and late phase of formalin-induced paw licking in mice.

Studies on the anti-inflammatory and related pharmacological properties of the aqueous extract of Bridelia ferruginea stem bark.

The anti-inflammatory profile of the aqueous extract of Bridelia ferruginea stem bark was investigated using both in vivo and in vitro models. The extract exhibited strong topical anti-inflammatory effect shown as inhibition of croton oil-induced ear oedema in mice, and reduced hind-paw swelling and growth retardation in the adjuvant-induced arthritis model in rats, following oral administration at 10, 20, 40 or 80 mg/kg. The extract (10-80 mg/kg, p.o.) caused an inhibition of increase in vascular permeability in both cyclophosphamide-induced haemorrhagic cystitis and acetic acid-induced vascular permeability in rats and mice, respectively. B. ferruginea produced stabilization of erythrocytes exposed to heat and stress-induced lysis. Antipyretic and analgesic properties of the extract were also observed.

Studies on the anti-inflammatory, antipyretic and analgesic properties of Alstonia boonei stem bark.

The methanol extract of the stem bark of Alstonia boonei was investigated for anti-inflammatory property. The analgesic and antipyretic properties of the extract was also evaluated. The extract caused a significant (P<0.05) inhibition of the carrageenan-induced paw oedema, cotton pellet granuloma, and exhibited an anti-arthritic activity in rats. Vascular permeability induced by acetic acid in the peritoneum of mice was also inhibited. The extract also produced marked analgesic activity by reduction of writhings induced by acetic acid, as well as the early and late phases of paw licking in mice. A significant (P<0.05) reduction in hyperpyrexia in mice was also produced by the extract. This study has established anti-inflammatory, analgesic and antipyretic activities of the stem bark of A. boonei.

Effects of the aqueous extract of Bridelia ferruginea stem bark on carrageenan-induced oedema and granuloma tissue formation in rats and mice.

The anti-inflammatory activity of the aqueous extract of the stem bark of Bridelia ferruginea was evaluated using carrageenan-induced paw oedema in rats and mice, and the cotton pellet granuloma method. The extract at doses ranging from 10 to 80 mg/kg p.o. significantly inhibited the carrageenan-induced rat paw oedema, with an ID50 value of 36 mg/kg. However, a low activity was produced in the mouse paw oedema. The extract also suppressed the granulomatous tissue formation of chronic inflammation. B. ferruginea therefore proved to be effective in both the acute and chronic phases of the inflammatory process.

Central nervous system depressant effect of Hoslundia opposita vahl.

The chloroform extract of the dried root of Hoslundia opposita has been evaluated for effects on the central nervous system (CNS). The extract significantly potentiated the phenobarbitone sleeping time in mice and produced a 60% protection against leptazol-induced convulsion. Neuropharmacological screening revealed CNS depression.

Biological effects of Myristica fragrans (nutmeg) extract.

The chloroform extract of nutmeg has been evaluated for antiinflammatory, analgesic and antithrombotic activities in rodents. The extract inhibited the carrageenan-induced rat paw oedema, produced a reduction in writhings induced by acetic acid in mice and offered protection against thrombosis induced by ADP/adrenaline mixture in mice.

Evaluation of the anti-diabetic property of Morinda lucida leaves in streptozotocin-diabetic rats.

The hypoglycaemic and anti-hyperglycaemic activities of a methanol extract of Morinda lucida Benth. (Rubiaceae) leaves were studied in normal and streptozotocin-diabetic rats. In normal rats, the extract demonstrated a significant (P < 0.05) and dose-dependent hypoglycaemic activity within 4 h after oral administration. The plasma glucose level of 400 mg kg(-1) of the extract at 4 h was 42.5 +/- 0.4 mg/100 mL (control 67.4 +/- 1.2 mg/100 mL). After 12 h, the plasma glucose level of rats administered 50, 100, 200 or 400 mg kg(-1) extract fell to 51.9 +/- 1.2, 47.3 +/- 0.8, 43.1 +/- 0.4 and 40.0 +/- 0.5 mg/100 mL, respectively. In hyperglycaemic rats, the extract produced a significant (P < 0.05) anti-diabetic effect from day 3 after oral administration, with 400 mg kg(-1) extract-treated animals having a plasma glucose level of 248.7 +/- 5.3 mg/100 mL compared with glibenclamide (10 mg kg(-1))-treated animals with a plasma glucose level of 251.5 +/- 5.8 mg/100 mL. These results suggest that the leaves of Morinda lucida have a strong glucose lowering property when administered to streptozotocin-treated rats.

Sensitivity of Plasmodium falciparum to mefloquine-sulphadoxine-pyrimethamine (Fansimef) in vivo and to mefloquine alone in vitro in Nigeria.

In Nigeria chloroquine remains the drug of choice for the treatment of falciparum malaria, since chloroquine resistance is not yet a problem. Nevertheless, in view of the rapid spread of multi-resistant Plasmodium falciparum in Africa it is desirable to test alternative drugs for efficacy and safety. To this end, we undertook a comparative controlled trial of the new triple combination, mefloquine-sulphadoxine-pyrimethamine (MSP, Fansimef) with chloroquine in a group of Nigerian children with symptomatic falciparum malaria. Our results showed that Fansimef was an effective blood schizontocide against the Nigerian strain of P. falciparum and was well tolerated. In particular, sinus bradycardia, which was frequently observed with Fanismef in the trials conducted in Zambia, was not seen in any of the Nigerian patients. In vitro sensitivity tests done on 26 P. falciparum isolates showed that all isolates were susceptible to complete inhibition by mefloquine, but the minimum concentration which produced complete inhibition in some isolates was higher than expected for fully sensitive parasites.

Effect of Solanum erianthum aqueous leaf extract on Plasmodium berghei in mice.

The aqueous leaf extract of Solanum erianthum collected in May was administered orally to albino Swiss mice infected with Plasmodium berghei berghei. The schizontocidal activity on early infection was assessed by administering the extract of S. erianthum, chloroquine, or distilled water as single daily dose from the day of infection for 4 days. Microscopic examination made on the fifth day from all the mice, showed S. erianthum extract producing a dose-related schizontocidal effect, with the highest having a chloroquine equivalent of 1.7 mg/kg. The residual activity of this extract was assessed by administering it to mice for 3 days prior to the day of inoculation with parasites. Seventy-two hours after infecting the mice, microscopic examination of the blood smears was made from all the mice. The extract produced dose-related activity. The highest dose and 1.2 mg/kg pyrimethamine produced 78.9 and 80.5% chemosuppression, respectively. Its effect on the established infection was studied by administering the drugs daily 72 h after infecting the mice, and for 5 days. The level of parasitaemia was assessed daily. The results show that the extract did not produce any significant suppression of infection. The observations are interesting and promising in view of the fact that the crude extract was used and also because controversy exists as to its usefulness as an anti-malarial agent.

Screening of Morinda lucida leaf extract for antimalarial action on Plasmodium berghei berghei in mice.

The leaf extract of Morinda lucida collected in August was administered subcutaneously to albino Swiss mice infected with P. berghei berghei. The schizontocidal activity on early infection was assessed by administering chloroquine (standard) distilled water or Morinda lucida as single daily dose on day 0-3 to infected mice. On day 4 the degree of parasitaemia and percentage was determined in relation to control. Its schizontocidal activity was also observed on an established infection by administering the drugs 72 h after infecting the mice and the degree of parasitaemia was determined daily. The repository action of pyrimethamine was also compared with Morinda lucida. On the early infection, the chloroquine equivalent of Morinda lucida was found to be 1.0 mg/kg. In established infection a daily increase in parasitaemia was observed in control group while the animals that received chloroquine (5 mg/kg) and 1/6 dilution of the stock of Morinda lucida extract showed a sharp fall in parasitaemia from the second day of treatment. For the prophylactic test, 1.2 mg/kg of pyrimethamine and 1/6 dilution of stock of extract produced 80.5% and 70% chemosuppression respectively. It is interesting to note that Morinda lucida leaves extract appears to have schizontocidal and repository effects in mice infected with P. berghei berghei.

Lack of schizontocidal activity of three herbal decoctions on Plasmodium berghei berghei in mice.

This work reports the effects of three herbal decoctions on Plasmodium berghei berghei in mice. The schizontocidal activity of each decoction was determined on an established infection using chloroquine as a standard and distilled water as control. Also a repository study of the decoction was carried out in another group of mice. The three decoctions neither reduced parasitaemia nor prolonged the life of infected mice that received them.

Effect of Azadirachta indica on Plasmodium berghei berghei in mice.

Azadirachta indica leaf extract has been investigated for antimalarial activity against drug sensitive strain of P. berghei berghei in mice. On administering the extract subcutaneously to infected mice in the "4-day schizontocidal test' 41.2% suppression of parasitaemia was observed. A similar observation was made when the extract was injected for 3 days before the animals were infected with the parasites, 21.7% chemosuppression was obtained. When treatment commenced after the infection had already established, there was no demonstrable suppression of parasitaemia.

Response of the non-pregnant and pregnant rat uterus to chloroquine in vitro.

The contractility of the uterus is known to vary at different phases of the oestrus cycle and during pregnancy. Chloroquine in low doses produced an initial reduction of the amplitude of spontaneous contraction followed by a dose-dependent increase in the amplitude of contraction and reduction in the rate of contraction of uteri in the proestrus, oestrus and dioestrus phases of the oestrus cycle. Reduction in both the rate and amplitude of contraction was recorded to higher doses on the uterus in the proestrus phase whilst a further increase in amplitude and reduction in rate of contraction were observed on uteri in oestrus and dioestrus phases. Chloroquine produced irregular non-dose-dependent spontaneous contractions of the quiet uterus in early pregnancy.