Spectrophotometric studies of a novel Gedunin-2-Hydroxypropyl- ß-cyclodextrin binary system.

BACKGROUND: Gedunin, a limonoid, is linked with antimalarial, anticancer and anti-allergic activities. This study was aimed at preparing an inclusion complex of gedunin and 2-hydroxypropyl-p-cyclodextrin (HBD) to increase solubility of-gedunin in polar solvents which will increase absorption and bioavailability in vivo and thus enhance pharmacological effects. MATERIALS AND METHODS: Gedunin was obtained from the hexane extract of Entandrophragma angolense heartwood by column and preparative thin layer chromatography. The structure was previously confirmed by spectroscopic means (NMR). The electronic absorption spectra data of the complexes formed between gedunin. and HBD in various solvents was determined using the UV-VIS spectrophotometer. The stoichiometry of inclusion was determined by Job's method of continuous variation. RESULTS: Evidence of interaction was observed between gedunin and HBD in the various solvents but gedunin and its complex with HBD exhibited sharp absorption bands in acetate buffer (pH 3.5).The spectrophotometric titrations showed curves with a single point of inflexion when the experiment was carried'out at 25°C (298 K) and 37°C (310 K). A stoichiometric ratio of 1:1 for complex formation was obtained. The formation constants (K,) obtained at 25°C and 37°C.were 9.539 x.10³ M⁻¹ and .1.853 x 104 M⁻¹ respectively. Thermodynamic considerations revealed hydrophobic interaction between gedunin and HBD. CONCLUSION: A stable inclusion complex of gedunin and HBD was formed at room and body temperature. This complex formation involved trapping of poorly soluble gedunin into the hydrophobic core of the cyclodextrin and may enhance the pharmacological activity of gedunin in vivo.

Pharmacological properties of the extract and some isolated compounds of Clausena lansium stem bark: anti-trichomonal, antidiabetic, anti-inflammatory, hepatoprotective and antioxidant effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Clausena lansium (Fool's Curry Leaf) is used for various ethnomedical conditions in some countries, including bronchitis, malaria, viral hepatitis, acute and chronic gastro-intestinal inflammation, and as a spicy substitute of the popular Curry leaf tree (Murraya koenigii). AIM OF THE STUDY: This study was to evaluate the ethnomedical uses of the stem bark in inflammatory conditions, hepatotoxicity and to determine the anti-diabetic and anti-trichomonal properties of the plant. MATERIALS AND METHOD: Anti-trichomonal, in vivo and in vitro antidiabetic and insulin stimulating, anti-inflammatory, hepatoprotective and anti-oxidant activities using Trichomonas gallinae, glucose loaded rats and in vitro insulin secreting cell line (INS-1 cell), carrageenin-induced rat paw oedema, CCl(4)-induced hepatotoxicity and DPPH scavenging ability methods respectively for the extracts and some isolates were determined. RESULTS: A dichloromethane extract was superior over methanolic extract with respect to an anti-trichomonal activity which was measured after 24 and 48 h. The isolated compounds imperatorin and 3-formylcarbazole had the main anti-trichomonal activity (LC(50)s of 6.0, 3.0 and 3.6, 9.7 microg/mL after 24 and 48 h, respectively). Methanolic extract (100 mg/kg) induced maximum and significant (p<0.05) anti-hyperglycaemic activity of 15.8% at 30 min and a 38.5% increase in plasma insulin at 60 min, compared to control. The increase in plasma insulin after 60 min, compared to 0 min, was 62.0% (p<0.05). The significant 174.6% increase of insulin release from INS-1 cells (in vitro) at 0.1 mg/ml indicates that it mediates its antidiabetic action mainly by stimulating insulin release. Imperatorin and chalepin were the major active constituents increasing in vitro insulin release to 170.3 and 137.9%, respectively. 100 mg/kg of the methanolic extract produced an anti-inflammatory activity after 4 h. A sedative effect was not observed. 100 and 200 mg/kg of methanolic extract administered i.p., reduced CCl4-induced hepatotoxicity firstly by 5.3 and 8.4% reduction in phenobarbitone-sleeping time respectively, secondly by reversing the reduction in serum liver proteins by 7.0-8.8%, serum AST, ALT and ALP activities by 27.7-107.9% and thirdly by diminishing increased values of plasma AST, ALT and ALP activities by 13.2-83.8%. The extract exhibited antioxidant activities. CONCLUSION: The hepatoprotective activity of C. lansium is partly due to its anti-oxidant and anti-inflammatory properties and confirms its folkloric use in the treatment of gastro-intestinal inflammation, bronchitis and hepatitis. In addition the use of C. lansium stem bark would be useful in diabetes and trichomoniasis.

Anti-protozoan activities of Harungana madagascariensis stem bark extract on trichomonads and malaria.

AIM OF THE STUDY: The ethanolic stem bark extract of Harungana madagascariensis (Hypericaceae), (Choisy) Poir were evaluated for their activities on Trichomonas gallinae (Rivolta) Stabler isolated from the pigeon (Columba livia). It was also tested for their anti-malarial activity on N67 Plasmodium yoelii nigeriensis (in vivo) in mice and on Plasmodium falciparum isolates in vitro. MATERIALS AND METHODS: The anti-trichomonal screening was performed in vitro using Trichomonas gallinae culture. The minimum lethal concentration (MLC) is the lowest concentration of the test extract in which no motile organisms were observed. The anti-malarial effects were determined in-vivo for suppressive, curative and prophylactic activities in mice receiving a standard inoculum size of 1 x 10(7) (0.2 ml) infected erythrocytes of Plasmodium yoelii nigeriensis intraperitoneally, and the in vitro was performed against 3 isolates of Plasmodium falciparum in a candle jar procedures. RESULTS: The IC(50) of the extract and metronidazole (MDZ) (Flagyl) on Trichomonas gallinae at 48 h are 187 and 1.56 microg/ml. The IC(50) of the extract, chloroquine (CQ) and artemether (ART) on Plasmodium falciparum are between 0.052 and 0.517 microg/ml for the extract and 0.021 and 0.0412 microg/ml for ART and CQ, respectively. The actions of the extract in in vivo study on Plasmodium yoelii nigeriensis showed that in both suppressive and prophylactic tests the percentages chemo-suppressive were between 28.6-44.8% and 30.2-78.2% respectively, while only 80 mg/kg of the extract reduced the parasitaemia level when compared to the control and the standard drugs in curative test. CONCLUSIONS: Harungana madagascariensis stem bark extract therefore exhibited significant anti-protozoan effects against Trichomonas and Plasmodium both in vivo and in vitro.

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

A study of the In Vivo activity of the leaf extract of Alchornea cordifolia against multiply antibiotic resistant S. aureus isolate in mice.

The effect of a 50% aqueous ethanol extract of Alchornea cordifolia (Schum and Thonn) Muell. Arg. leaf was investigated in mice which had been infected intraperitoneally with 5.0 x 10(9) cfu of Staphylococcus aureus. Dose-dependent antibacterial activity was demonstrated and the rate of survival of infected mice was improved significantly by doses between 25 and 200 mg/kg of injected extract when compared with untreated infected controls. The intraperitoneal median lethal dose of the extract was found to be 800 mg/kg.

Antimicrobial and Antioxidant Activities of Some Nigerian Medicinal Plants

Ten Nigerian plants suggested from their ethnomedical uses to possess antimicrobial and antioxidant activities were studied for their anti-microbial and anti-oxidant properties. Antimicrobial activity was tested against Escherichia coli NCTC 10418, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, Candida albicans, Candida pseudotropicalis and Trichophyton rubrum (clinical isolate). Trichilia heudelotti leaf extract showed both antibacterial and antifungal activities and was the most active against all the strains of bacteria tested. Boerhavia diffusa, Markhamia tomentosa and T. heudelotti leaf extracts inhibited the gram negative bacteria E.coli and P. aeruginosa strains whereas those of M. tomentosa, T. heudelotti and Sphenoceutrum jollyamum root inhibited at least one of the fungi tested. At a concentration of 312 µg/ml, hexane and chloroform fractions of T. heudelotti extract inhibited 6 and 14% of the fifty mult-idrug resistant bacteria isolates from clinical infectins, respectively. At ≤ 5mg/ml, the CHCl3 (64%) and aqueous (22%) fractions of T. heudelotti and those of CHCl3 (34%) and EtOAC (48%) of M. tomentosa gave the highest inhibition that was stronger than their corresponding methanol extracts. The corresponding EC50 of the extracts on M. acuminata, T. heudelotti, E. senegalensis and M. tomentosa were 4.00, 6.50, 13.33, and 16.50 ig/ml using the TLC staining and 1,1-dipheyl-2-picry-hydrazyl (DPPH) free radical scavenging assay. Therefore, leaf extracts of M. tomentosa and T. heudelotti, especially the latter, possess strong antimicrobial and antioxidant activities and should be further investigated. These activities justified the ethnomedical uses of these plants

Changes in the visceral functions of Plasmodium berghei-infected and -uninfected rats following administration of artemether.

1. The effects of artemether (12.5, 25.0 and 50.0 mg/kg per day, i.m.), administered to different groups of Plasmodium berghei-infected and -uninfected adult Wistar rats for 1 week, were investigated. 2. The parameters evaluated were the feeding, drinking and urinating patterns of the rats and these were compared with those of rats that received normal saline. 3. Artemether caused a significant dose-dependent reduction in food consumption of both P. berghei-infected and -uninfected rats (P < 0.05). Food intake in infected rats was reduced by approximately 7 g/24 h. This reduction in food intake was further reduced during drug treatment with artemether. Artermether also reduced food intake in uninfected rats. The food consumption of rats that received 12.5 and 25.0 mg/kg artemether was restored after stopping treatment, in contrast with rats that received 50.0 mg/kg, in which the significant reduction in food consumption persisted 1 week after drug administration. 4. During treatment with artemether, the water intake of infected rats was significantly lower than that of uninfected rats in the 12.5 mg/kg artemether-treated group, but was significantly higher in infected rats than in uninfected rats dosed with 25.0 and 50.0 mg/kg artemether. 5. For all doses of artemether tested, a significant increase in urine output was observed in infected rats during treatment and 1 week after treatment, whereas in uninfected rats a significant increase in urine output was observed only following 25.0 and 50.0 mg/kg artemether 1 week after drug administration. 6. The present study confirms the anorexic activity of a high dose of artemether in both P. berghei-infected and -uninfected rats. It also indicates that high doses of the drug could cause impaired renal function in rats and that the significant increase in urine output could also be due to other effects of artemether, namely those on thirst, anti-diuretic hormone output and the osmotic pressure of the blood.

Anti-trichomonal, biochemical and toxicological activities of methanolic extract and some carbazole alkaloids isolated from the leaves of Murraya koenigii growing in Nigeria.

The methanolic extract of Murraya koenigii leaf was screened for toxicological and biochemical effects on rats because of the folkloric uses as an anti-dysentery and anti-diabetes. The extract was moderately toxic (LD(50)=316.23 mg/kg body weight) to rats and had appreciable effect on the liver and kidney at higher doses leading to liver inflammation. It had little or no effect on haematology and relative organ weight of lungs, heart and spleen. Acute doses (500 mg/kg) reduced significantly serum globulin, albumin, urea, glucose, total protein, aspartate transaminase (AST), and increased cholesterol and alanine transaminase (ALT) indicating hepatic injury. However, chronic administration for 14 days gave a significant (p<0.05) reduction in the serum cholesterol, glucose, urea, bilirubin, ALT and AST showing that the plant has hypoglycaemic and hepatoprotective effects after prolonged use. The activity demonstrated by some of the isolated carbazole alkaloids and their derivatives against Trichomonas gallinae confirmed that the anti-trichomonal activity of the leaf may be due to its carbazole alkaloids. The order of activity was C(18)>C(23)>C(13). Girinimbine and girinimbilol with IC(50) values of 1.08 and 1.20 microg/ml were the most active. Acetylation of girinimbilol and mahanimbilol improved their activities to 0.60 and 1.08 microg/ml.

Antimicrobial and antioxidant activities of some Nigerian medicinal plants.

Ten Nigerian plants suggested from their ethnomedical uses to possess antimicrobial and antioxidant activities were studied for their anti-microbial and anti-oxidant properties. Antimicrobial activity was tested against Escherichia coli NCTC 10418, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, Candida albicans, Candida pseudotropicalis and Trichophyton rubrum (clinical isolate). Trichilia heudelotti leaf extract showed both antibacterial and antifungal activities and was the most active against all the strains of bacteria tested. Boerhavia diffusa, Markhamia tomentosa and T. heudelotti leaf extracts inhibited the gram negative bacteria E. coli and P. aeruginosa strains whereas those of M. tomentosa, T. heudelotti and Sphenoceutrum jollyamum root inhibited at least one of the fungi tested. At a concentration of 312 microg/ml, hexane and chloroform fractions of T. heudelotti extract inhibited 6 and 14% of the fifty multi-drug resistant bacteria isolates from clinical infections, respectively. At < or = 5 mg/ml, the CHCl(3) (64%) and aqueous (22%) fractions of T. heudelotti and those of CHCl(3) (34%) and EtOAC (48%) of M. tomentosa gave the highest inhibition that was stronger than their corresponding methanol extracts. The corresponding EC(50) of the extracts on M. acuminata, T. heudelotti, E. senegalensis and M. tomentosa were 4.00, 6.50, 13.33, and 16.50 ig/ml using the TLC staining and 1,1-dipheyl-2-picry-hydrazyl (DPPH) free radical scavenging assay. Therefore, leaf extracts of M. tomentosa and T. heudelotti, especially the latter, possess strong antimicrobial and antioxidant activities and should be further investigated. These activities justified the ethnomedical uses of these plants.

Antinociceptive; anti-inflammatory and cytotoxic activities of Pentaclethra macrophylla aqueous extracts in mice

The aqueous leaf; stem - bark; seed and fruit pericarp extracts of Pentaclethra macrophylla were examined for their cytotoxicity; while only the leaves and seeds were tested for analgesic and anti-inflammatory activities using in-vivo and in-vitro experimental models. Cytotoxicity haemagglutination assay revealed the following order of toxicity among the plant parts: fruit pericarp stem - bark seed leaf with 71.4; 25.6; 5.3; and 0.5 haemagglutination titre values respectively. The extracts at 30 and 60 mg/kg exhibited analgesic activity and anti-inflammatory property using the flick and hot plate tests; acetic acid induced writhing test; and leucocyte counts; pulmonary oedema and oedema paw of mice in a dose-dependent manner. These findings therefore explain and justify ethnomedical uses of Pentaclethra macrophylla in the treatment of itching (inflammatory response) and pain in animals and in man

Pro- and antioxidant effects and cytoprotective potentials of nine edible vegetables in southwest Nigeria.

Antioxidant and cytoprotective activities of boiled, cold, and methanolic extracts of nine edible vegetables in Southwest Nigeria were evaluated in the 1,1-diphenyl-2-picrylhydrazyl free radical assay and hemagglutination assay in bovine erythrocytes, respectively. Crassocephalum rubens showed the highest antioxidant activity (56.5%), Solanum americanum and Vernonia amygdalina exhibited moderate antioxidant activity (26.0-37.5% and 14.8-36.2%, respectively), Solanum macrocarpon, Telfaria occidentalis, Amaranthus hybridus, and Jatropha tanjorensis produced weak activity (1.6-15.8%, 1.6-7.7%, 2.8-6.62%, and 10.7-12.1%, respectively), while Celosia argentea and Talinum triangulare were pro-oxidants. It was also shown that extracts from all the vegetables are pro-oxidants at high concentrations of either 1 or 5 mg/mL or both. On the other hand, the studies on the cytoprotective effect showed that all the plant extracts demonstrated a very low hemagglutination titer value between 0.32 and 5.56 except S. americanum methanolic extract, which had a titer of 50.0. These results indicated correlation between the antioxidant properties and the hemagglutination values of these plant extracts; however, the membrane stabilizing capacity of the extracts supports the plants' antioxidant activity.

Antitrichomonal and antioxidant activities of Dorstenia barteri and Dorstenia convexa.

Dorstenia barteri and D. convexa extracts and some isolated components of the former were investigated for effectiveness against Trichomonas gallinarum and compared with quercetin and quercitrin. The antioxidant activity of the extracts/compounds was also determined. The minimum lethal concentrations (MLCs) for the extract of D. barteri leaves and twigs at 24 h were found to be 15.625 and 15.625 microg/ml, respectively. However, the MLCs of the leaf and twig extract of D. convexa were 125 and 437.5 microg/ml, respectively. The prenylated and geranylated chalcones were as active as the prenylated flavones, 6-prenylapigenin and the diprenylated derivative 6,8-diprenyleridictyol. The order of the antitrichomonal activity of the compounds at 24 h was: quercetin (0.121 microg/ml) > quercitrin (0.244 microg/ml) > or = bartericin B (0.244 microg/ml) > bartericin A (0.73 microg/ml) > stigmasterol (0.98 microg/ml) > 6,8-diprenyleridictyol = isobavachalcone = dorsmanin F (31.25 microg/ml). D. barteri extracts, quercitrin, and bartericin A, and the prenylated flavonoids had potent antioxidant properties. The twig extract of D. barteri was more potent than the leaf extract. Moderate (EC50 >50 microg/ml) and high (EC50 <50 microg/ml) antioxidant activities were detected in the leaf and twig extracts of D. barteri and the prenylated flavonoids. Prenylated flavonoids and the isolated compounds with antioxidant properties described here may account for the anti-inflammatory action of these extracts. The antitrichomonal and antioxidant activities shown by the extracts and compounds in this study are consistent with the ethnomedicinal and local use of the Dorstenia species studied.

Antitrichomonal and antioxidant activities of Dorstenia barteri and Dorstenia convexa

Dorstenia barteri and D. convexa extracts and some isolated components of the former were investigated for effectiveness against Trichomonas gallinarum and compared with quercetin and quercitrin. The antioxidant activity of the extracts/compounds was also determined. The minimum lethal concentrations (MLCs) for the extract of D. barteri leaves and twigs at 24 h were found to be 15.625 and 15.625 æg/ml, respectively. However, the MLCs of the leaf and twig extract of D. convexa were 125 and 437.5 æg/ml, respectively. The prenylated and geranylated chalcones were as active as the prenylated flavones, 6-prenylapigenin and the diprenylated derivative 6,8-diprenyleridictyol. The order of the antitrichomonal activity of the compounds at 24 h was: quercetin (0.121 æg/ml) > quercitrin (0.244 æg/ml) > or = bartericin B (0.244 æg/ml) > bartericin A (0.73 æg/ml) > stigmasterol (0.98 æg/ml) > 6,8-diprenyleridictyol = isobavachalcone = dorsmanin F (31.25 æg/ml). D. barteri extracts, quercitrin, and bartericin A, and the prenylated flavonoids had potent antioxidant properties. The twig extract of D. barteri was more potent than the leaf extract. Moderate (EC50 >50 æg/ml) and high (EC50 <50 æg/ml) antioxidant activities were detected in the leaf and twig extracts of D. barteri and the prenylated flavonoids. Prenylated flavonoids and the isolated compounds with antioxidant properties described here may account for the anti-inflammatory action of these extracts. The antitrichomonal and antioxidant activities shown by the extracts and compounds in this study are consistent with the ethnomedicinal and local use of the Dorstenia species studied.

Antinociceptive and anti-inflammatory effects of Dorstenia barteri (Moraceae) leaf and twig extracts in mice.

The present study was undertaken to investigate the antinociceptive and anti-inflammatory activities of the leaf and twig extracts of Dorstenia barteri (Moraceae) in mice. Both the leaf and twig extracts of Dorstenia barteri at 50, 100 and 200 mg/kg showed significant (P < 0.05-0.01) antinociceptive activities in chemical-, mechanical- and thermal-induced pain test models. Intraperitoneal administration of the plant extracts at 50, 100 and 200 mg/kg significantly (P < 0.05-0.01) inhibited carrageenin-induced acute inflammation in oedema paw weight, pulmonary oedema and number of pleural leucocytes in a dose-dependent way. The twig extract was found to be more active than the leaf extract in all the experimental models used. The inhibitory effects of the plant extracts were comparable to those of the reference drugs acetylsalicyclic acid (ASA) and phenylbutazone (PBZ) at 100 mg/kg i.p. The significant reduction in acetic acid-induced abdominal contractions, the decrease in oedema paw weight as well as in the number of leucocytes in the pleural cavity exudates, and the significant increase in the reaction time and pain threshold of mice observed in this study suggest that Dorstenia barteri extracts possess both anti-inflammatory and antinociceptive activities. The present study, therefore, lend pharmacological support to the folkloric uses of Dorstenia barteri extracts in the treatment, control and/or management of arthritis, rheumatism, gout, headache and other forms of body pains in some parts of Africa.

Effects of autacoid inhibitors and of an antagonist on malaria infection in mice

The effects of p-chlorophenylalanine, an inhibitor of serotonin synthesis, indomethacin, an inhibitor of prostaglandin synthesis, cyproheptadine, a serotonin, bradykinin and histamine antagonist, were assessed separately and in combination with chloroquine (CQ) in Vom strains of Swiss albino mice (18-22 g) of either sex infected intraperitoneally with 1 x 10(7) Plasmodium yoelii nigeriensis-induced malaria. As prophylactic, these agents reduced from 31.9 ± 4.5 to 16.1 ± 8.1 percent the level of parasitemia relative to control but had no appreciable activity as curative agents when administered subcutaneously once daily for 4 days after 72 h of parasites innoculum in vivo. However, CQ alone and the combination of these agents with CQ in curative and prophylactic treatments significantly reduced (from 50.3 ± 5.8 to 4.9 ± 0.75 percent) the level of parasitemia (P < 0.05), which was taken only once 72 h after the parasites innoculum. The prophylactic result was shown to produce better results than the curative treatment. The data indicate that inhibitors and an antagonist can reduce the parasitemia load (the extent of damage and the severity of infection) as well as enhance the effects of CQ when combined with it for malaria therapy. The study reveals that the production of autacoids in established infection renders autacoid inhibitors and an antagonist ineffective for radical cure in malarial mice; however, selective inhibition of local hormones implicated in the pathological manifestations of malaria infection by autacoid inhibitors and an antagonist may be a possible pathway to reduce the severity of infection and the associated tissue damage and to enhance the efficacy of available anti-malarials.

Effects of autacoid inhibitors and of an antagonist on malaria infection in mice.

The effects of p-chlorophenylalanine, an inhibitor of serotonin synthesis, indomethacin, an inhibitor of prostaglandin synthesis, cyproheptadine, a serotonin, bradykinin and histamine antagonist, were assessed separately and in combination with chloroquine (CQ) in Vom strains of Swiss albino mice (18-22 g) of either sex infected intraperitoneally with 1 x 10(7) Plasmodium yoelii nigeriensis-induced malaria. As prophylactic, these agents reduced from 31.9 +/- 4.5 to 16.1 +/- 8.1% the level of parasitemia relative to control but had no appreciable activity as curative agents when administered subcutaneously once daily for 4 days after 72 h of parasites innoculum in vivo. However, CQ alone and the combination of these agents with CQ in curative and prophylactic treatments significantly reduced (from 50.3 +/- 5.8 to 4.9 +/- 0.75%) the level of parasitemia (P < 0.05), which was taken only once 72 h after the parasites innoculum. The prophylactic result was shown to produce better results than the curative treatment. The data indicate that inhibitors and an antagonist can reduce the parasitemia load (the extent of damage and the severity of infection) as well as enhance the effects of CQ when combined with it for malaria therapy. The study reveals that the production of autacoids in established infection renders autacoid inhibitors and an antagonist ineffective for radical cure in malarial mice; however, selective inhibition of local hormones implicated in the pathological manifestations of malaria infection by autacoid inhibitors and an antagonist may be a possible pathway to reduce the severity of infection and the associated tissue damage and to enhance the efficacy of available anti-malarials.

An in vitro study of the effects of Cassia podocarpa fruit on the intestinal motility of rats.

Folkloric evidence and scientific reports indicate the use of C. podocarpa fruit as a purgative recipe. This study attempts to find the in vitro effects of its aqueous infusion (ACPF) and methanolic extract (MCPF) on the motility of the intestine of albino rats of Wistar strain and to compare their effect with those of C. acutifolia fruit (ACAF and MCAF). MCPF relaxed both the ileum and colon dose dependently. Its effect was blocked by tolazoline (10(-9) M) and propranolol (10(-9) M). ACPF had no effect on the ileum, but contracted the colon dose-dependently. Its effect was blocked by nifedipine (2.8 x 10(-10) M) and drastically reduced by atropine (3.4 x 10(-6) M). MCAF has the same effect as ACPF on both ileum and colon and its effect was similarly affected by atropine (3.4 x 10(-6) M) and nifedipine (2.8 x 10(-8) M). ACAF relaxed the ileum, its effect was blocked by tolazoline (5.1 x 10(-7) M). MCAF was more potent than ACPF in contracting the colon, Hexamethonium (2.8 x 10(-8) M), chlorpheniramine (3.8 x 10(-8) M) and promethazine (3.2 x 10(-10) M) potentiated the effect of ACPF on the colon. The results suggest that both ACAF and MCPF have anti-diarrhoeal effect. MCPF acts via both alpha and beta adrenergic receptor stimulation, while ACAF stimulates alpha-receptor. ACPF and MCAF engage both the cholinergic system and calcium channel activation in causing purgation in the colon. The potentiation of the effect of ACPF by some blockers could be due to allosteric enhancement of the receptors involved in its action.

Studies on the acute and sub-chronic toxicity of the essential oil of Ocimum gratissimum L. leaf.

Oral and intra-peritoneal acute toxicity and the sub-chronic intra-peritoneal toxicity of the essential oil of Ocimum gratissimum Linn, Lamiaceae (Ocimum oil), was investigated. The acute toxicity test involved the oral and intra-peritoneal administration of graded doses of Ocimum oil prepared as a 4% v/v emulsion to 2 groups each of 30 rats and mice. LD50 and LD100 were determined for both routes and species. In the sub-chronic toxicity study, 25 male Sprague-Dawley rats were randomized into 4 test groups (treated with three graded sub-lethal doses of Ocimum oil prepared as a 4% v/v emulsion) and a control. Organs and blood samples were taken for analyses after a 30 day treatment period. A dose-dependent sedative effect of Ocimum oil was observed during the acute toxicity study in mice and rats and in the sub-chronic test in rats. Evidence of treatment, route, and dose-dependent toxicity were detected in both studies. Changes in weight of the testes, hearts, kidneys, intestines and lungs of the rats were statistically insignificant (ANOVA P < 0.05). Data analyses of blood biochemical, haematological and histopathological findings showed significant differences between control and treated groups and revealed that Ocimum oil is capable of invoking an inflammatory response that transits from acute to chronic on persistent administration. While the study revealed that Ocimum oil might be better tolerated when administered orally for systemic delivery, the oil has toxic potentialities that should not be overlooked.