Hypertensive effects of oral administration of the aqueous extract of Solanum torvum fruits in L-NAME treated rats: evidence from in vivo and in vitro studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Solanum torvum fruits are commonly used in Cameroonian traditional medicine for treatment of arterial hypertension. It has been previously shown that intravenous administration of aqueous extract from dried fruits (AEST) reduced blood pressure. AIM: The present work evaluates acute toxicity and effects of oral administration of AEST in chronic arterial hypertension induced by L-NAME. Effects of AEST were also evaluated on isolated aorta. MATERIALS AND METHODS: AEST (200 mg/kg/day, p.o.) was given solely or concomitantly with L-NAME (40 mg/kg/day, p.o.) for 30 consecutive days. Animal body weight, systolic blood pressure and heart rate were measured before stating the treatment and at the end of each week. Urinary volume and urinary sodium and potassium contents were quantified before and at days 1, 15 and 30 of the treatment. Aorta from treated animals was tested for their sensitivity to noradrenaline and carbachol. Aorta from normal untreated rats was used to evaluate the in vitro vascular effect of AEST. RESULTS: The results showed that AEST did induce neither mortality nor visible signs of toxicity. When given solely or in co-administration with L-NAME, AEST significantly reduced animal's body weight. It amplified the hypertensive and cardiac hypertrophy effect of L-NAME and did not affect these parameters in normotensive animals. AEST increased the sensitivity to noradrenaline in normotensive and significantly reduced it in hypertensive animals. AEST significantly increased urinary volume and sodium excretion in L-NAME treated animals while reducing the sodium excretion in normotensive. In vitro, AEST induced a potent partial endothelium-dependent contraction of aortic ring; contractions that were partially antagonized by prazosin and verapamil and were not relaxed by carbachol. CONCLUSION: These results suggest that oral chronic administration of AEST induced potentiation of arterial hypertension and cardiac hypertrophy in L-NAME treated rats. These effects may result from a reduction in sensitivity to vasorelaxant agents and increase in hypersensitivity to contractile factors. AEST possess potent in vitro vasocontractile activity that may result from activation of both alpha(1)-adrenergic pathway and calcium influx.

Anti-oxidative and anti-inflammatory activities of some isolated constituents from the stem bark of Allanblackia monticola Staner L.C (Guttiferae).

Stem bark of Allanblackia monticola has been used in association with others plant in the Cameroonian folk medicine for the treatment of various diseases such amoebic dysentery, diarrhoea, lung infections, and skin diseases. The methylene chloride fraction, its isolated compounds like alpha-mangostin, lupeol and acid betulinic were screened for antioxidant activity using free radical scavenging method. These isolated compounds were further tested for anti-inflammatory properties using carrageenan-induced model. Methylene chloride fraction, showed concentration-dependent radical scavenging activity, by inhibiting 1,1-diphenyl-1-picryl-hydrazyl radical (DPPH) with an IC(50) value of 14.60 microg/ml. alpha-Mangostin and betulinic acid (500 microg/ml), showed weak radical scavenging activity with a maximum inhibition reaching 38.07 microg/ml and 26.38 microg/ml, respectively. Betulinic acid, lupeol and alpha-mangostin (5 mg/kg and 9.37 mg/kg) showed anti-inflammatory activity with a maximum inhibition of 57.89%, 57.14% and 38.70%, respectively. Methylene chloride fraction of Allanblackia monticola and some derivatives, have antioxidant and anti-inflammatory activities.

Anti-hypertensive effects of the methanol/methylene chloride stem bark extract of Mammea africana in l-NAME-induced hypertensive rats.

AIM OF THE STUDY: The methanol/methylene chloride (CH(3)OH/CH(2)Cl(2)) extract from the stem bark of Mammea africana was showed to possess vasodilating effect in the presence and the absence of N(omega)-nitro-l-arginine methyl ester (l-NAME). The present study was designed to evaluate the effects of the methanol/methylene chloride from the stem bark of Mammea africana. MATERIALS AND METHODS: The extract (200 mg/(kg day)) was administered orally in rats treated concurrently with l-NAME (40 mg/(kg day)). l-Arginine (100 mg/(kg day)) and captopril (20 mg/(kg day))were used as positive controls. Bodyweight, systolic arterial blood pressure and heart rate were measured weekly throughout the experiment period (28 days). At the end of treatment, animals were killed and the cardiac mass index evaluated. The aorta was used to evaluate the endothelium-dependant relaxation to carbachol. The aorta contraction induced by noradrenalin was also examined and expressed as a percentage of that induced by KCl. RESULTS: The extract neither affected the body weight nor the heart rate. The extract as captopril completely prevented the development of arterial hypertension. Both the substances failed to restore the endothelium-dependent vascular relaxation and increased the vascular contraction to norepinephrine in relation to KCl contraction. They also significantly reduced the left ventricular hypertrophy induced by l-NAME. CONCLUSION: These findings are in agreement with the traditional use of Mammea africana in the treatment of arterial hypertension and indicate that it may have a beneficial effect in patients with NO deficiency but will be unable to improve their endothelium-dependent vasorelaxation.

Antimalarial and vasorelaxant constituents of the leaves of Allanblackia monticola (Guttiferae).

Phytochemical investigation of the leaves of Allanblackia monticola led to the isolation and characterisation of five prenylated xanthones [1,6-dihydroxy-3,7-dimethoxy-2-(3-methylbut-2-enyl)xanthone 1, alpha-mangostin 2, tovophyllin A 3, allanxanthone C 4 and 1,7-dihydroxy-3-methoxy-2-(3-methylbut-2-enyl)xanthone 5], two biflavonoid derivatives (amentoflavone 6 and podocarpusflavone A 7) and one pentacyclic triterpene (friedelan-3-one 8). The structures of these compounds were established on the basis of homo- and hetero-nuclear, one- and two-dimensional, nuclear magnetic resonance. Compounds 2-8 and a crude methanolic extract of A. monticola leaves were each tested for antimalarial activity in vitro, using the chloroquine-sensitive F32 and chloroquine-resistant FcM29 strains of Plasmodium falciparum; the median inhibitory concentrations (IC(50)) recorded varied from 0.7 to 83.5 mug/ml. The cytotoxicities of the compounds and crude extract, against cultures of human melanoma cells (A375), were then investigated, and cytotoxicity/antimalarial IC(50) ratios of 0.6-16.75 were recorded. In tests involving aortic rings from guinea pigs, a crude extract of the leaves of A. monticola was found to induce concentration-dependent vasorelaxation, causing up to 82% and 42% inhibition of noradrenaline- and KCl-induced contractions, respectively. The corresponding values for compounds 2 and 6 when tested against noradrenaline-induced contractions were approximately 18% and 35%, respectively.

Vasodilator effect of the extracts and some coumarins from the stem bark of Mammea africana (Guttiferae).

CH(2)Cl(2) fraction obtained from the stem bark of Mammea africana inhibited noradrenaline (NA) or KCl-induced contraction in isolated guinea pig and rat aorta. The vasorelaxant potency of the CH(2)Cl(2) fraction of Mammea africana was diminished by a pre-treatment with Nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase, which was however not affected by indomethacin pre-treatment. These findings indicated that the vasorelaxant effect of Mammea africana may be partially endothelium dependent, mediated by nitric oxide and that vasoactive prostanoids might not be contributing to the vasorelaxation effect. Three bioactive compounds were isolated from this CH(2)Cl(2) fraction and identified as 4-n-propylcoumarins (1) (mammea B/BB), 4-phenylcoumarins (2) (mammea A/AA or mammeisin) and (B/BA) (3) and might involved in the vasorelaxant effect of the extract. The mechanisms of the vasorelaxant effect might therefore be multiple, including endothelium dependence and the mechanisms, which interfere with the liberation of Ca(2+) into the muscle cell.

Analgesic and anticonvulsant effects of extracts from the leaves of Kalanchoe crenata (Andrews) Haworth (Crassulaceae).

Kalanchoe crenata Andr. (Crassulaceae) is a fleshy herbaceous plant used in the African traditional medicine as remedies against otitis, headache, inflammations, convulsions and general debility. In the present work, the analgesic effects of methylene chloride/methanol (1:1) (CH(2)Cl(2)/CH(3)OH) extract and its hexane, methylene chloride (CH(2)Cl(2)), ethyl acetate, n-butanol fractions and aqueous residue have been evaluated using acetic acid, formalin and pressure test. The anticonvulsant effects of the CH(2)Cl(2)/CH(3)OH extract were also investigated on seizures induced by pentylenetetrazol (PTZ 70 mg/kg), strychnine sulphate (STN 2.5 mg/kg) and thiosemicarbazide (TSC 50 mg/kg). CH(2)Cl(2)/CH(3)OH extract and its fractions, administered orally at the doses of 150 and 300 mg/kg, exhibited protective effect of at least 30% on the pain induced by acetic acid. The CH(2)Cl(2) fraction at 300 mg/kg showed a maximal effect of 78.49%. The CH(2)Cl(2)/CH(3)OH extract and its CH(2)Cl(2) fraction at the doses of 150 and 300 mg/kg significantly reduced the first phase of pain induced by formalin while the second phase was completely inhibited. The CH(2)Cl(2) fraction produced more than 45% reduction in the sensitivity to pain induced by pressure. The CH(2)Cl(2)/CH(3)OH extract of Kalanchoe crenata significantly increased the latency period in seizures induced by PTZ and significantly reduced the duration of seizures induced by the three convulsant agents. The extract protected 20% of animals against death in seizures induced by TSC and STN. These results suggest a peripheral and central analgesic activities as well as an anticonvulsant effect of the leaves of Kalanchoe crenata.

Antinociceptive and anti-inflammatory activities of Acacia pennata wild (Mimosaceae).

The butanolic fraction of dried leaves of Acacia pennata (Mimosaceae) was tested for analgesic and anti-inflammatory activities in animal models. It showed significant protective effects against chemical stimuli (acetic acid and formalin) in the mouse. It also produced a significant increase of the threshold of sensitivity to pressure-induced pain in the rats. The extract revealed an inhibitory effect in carrageenin-induced rat paw oedema in the late phase. The results suggested that a peripheral mechanism is involved in the analgesic, associated to anti-inflammatory effect (NSAIDs-like). Among the class of compounds characterized in this fraction, flavonoids may be mainly responsible for the pharmacological activities.

Anti-inflammatory and analgesic properties of the stem bark extract of Mitragyna ciliata (Rubiaceae) Aubrév. & Pellegr.

Mitragyna ciliata is widely used in traditional medicine for the treatment of inflammation, hypertension, headache, rheumatism, gonorrhoea and broncho-pulmonary diseases. In the present study, the anti-inflammatory and analgesic properties of the stem bark extract of M. ciliata were investigated. The stem bark of this plant was extracted over Soxhlet with hexane followed by another extraction with methanol. The resulting methanol extract was used for the pharmacological test. Anti-inflammatory activity was evaluated on the basis of the inhibitory effect of the extract on 5-lipoxygenase, and carrageenin-induced hind paw oedema in the rat. The methanol extract, at a dose of 19.2 microg/ml, exhibited no inhibition on 5-lipoxygenase. However, this extract administered per os (50 mg/kg) produced about 70% inhibition of carrageenin-induced paw oedema 1 h after administration. This inhibition was maintained to about 50% 2 h after administration. The dose of 50 mg/kg of MeOH extract significantly decreased sensitivity to pain from 78.75 to 107.5 g These findings suggest that extracts of the bark of M. ciliata, possess potent anti-inflammatory and analgesic effects. Chemical analysis of the extract showed the presence of alkaloids and kaempferol derivative which may be responsible for the anti-inflammatory properties.

[Comparative titration of three antivenin serums used against sub-Saharan African snakes]. / Titrage comparatif de trois sérums antivenimeux utilisés contre les serpents d'Afrique sub-saharienne.

The standardisation of serotherapy is necessary in Africa mainly because of the frequency of envenomations and the lack of alternative treatments. Comparative titrations of FAV-Afrique (Aventis Pasteur), Polyvalent serum (Serum Institute of India = SII) and Polyvalent antivenin (South African Vaccine Fabricants Ltd = SAIMR) were carried out on venoms of Echis ocellatus from Cameroun, E. ocellatus from Mali, E. leucogaster and Naja melanoleuca. The 50% protective doses (ED50) of the antivenoms were given according either to i) the in vitro method which consists of inoculating 5 batches of 5 mice with a mixture containing 3 DL50 of venom and increasing volumes of antivenom incubated for 30 mn at 37 degrees C and ii) the in vivo method which consists of successive administration of venom and then antivenom after a 30 to 60 mn interval. The three antivenoms showed a similar efficacy against all the Echis venoms. Interestingly, the SAIMR proved to be effective against the venom of E. leucogaster and E. ocellatus although no venom of Echis was used to immunise horses during the preparation of antivenom. Conversely, this paraspecificity did not exist with the Naja melanoleuca venom against which FAV Afrique showed a higher efficacy. The electrophoresis pattern of FAV-Afrique performed on acetate gel strips showed only one protein fraction (76 g.l-1), whereas both the SII and SAIMR antivenoms showed four fractions whose protein concentrations was respectively 64 g.l-1 and 145 g.l-1.

Vasodilating properties of extracts from the leaves of Musanga cecropioides (R. Brown).

The mechanisms of action involved in the hypotensive properties of the aqueous extract of the leaves of Musanga cecropioides were investigated. The effect of the aqueous leaf extract of M. cecropioides, found to contain mostly saponins, flavonoids and procyanidins, was investigated on vascular smooth muscle and also in an in vivo direct invasive blood pressure study in both normotensive and hypertensive rats. The hypotensive or antihypertensive properties of the extracts appear to be due partly to a direct or indirect vasodilator effect and also to some alpha(1)- and beta(2)-adrenergic blocking effects. The extract also exhibited significant endothelium-dependent vascular smooth muscle relaxation, accounted for by the release of nitric oxide (NO), and induced significant angiotensin converting enzyme (ACE) inhibitory effects thereby supporting its vasodilator mechanism of action.

Anti-inflammatory and analgesic properties of the stem bark extracts of Erythrophleum suaveolens (Caesalpiniaceae), Guillemin & Perrottet.

The MeOH stem bark extract of Erythrophleum suaveolens dissolved in water and shaken up with ethylacetate (EtOAc) and fractionated on a polyamide column with methanol as eluent produced five principal fractions. These fractions were designated as fraction A (74.8 mg yield and rich in alkaloids), fraction B (36.6 mg), fraction C (7.8 mg yield, monomeric procyanidin), fraction D (26.6 mg yield, rich in monomeric and oligomeric procyanidin), and fraction E (18.1 mg yield, rich in polymeric procyanidin). The original MeOH extract administered (100 mg/kg po) produced about 47% inhibition of carrageenin-induced paw oedema 1 h after administration. Fraction D, obtained from the ethylacetate extract and rich in procyanidins produced over 33% inhibition of carrageenan-induced paw oedema while a dose of 19.2 microg/ml produced 100% inhibitory effect on 5-lipoxygenase. A dose of 100 mg/kg of the MeOH extract also produced over 30% reduction of the sensitivity to pain while 50 mg/kg of fraction D rich in procyanidins produced over 45% analgesic effects. These results were judged significant compared to those obtained with indomethacin and acetylsalicylic acid. These findings suggest that extracts of the bark of Erythrophleum suaveolens possess potent anti-inflammatory and analgesic property and that the procyanidins lead to the observable pharmacological effects.

Antihypertensive effects of Dorstenia psilurus extract in fructose-fed hyperinsulinemic, hypertensive rats.

We examined the effect of methanol/methylene chloride extract of Dorstenia psilurus given by gastric intubation on systolic blood pressure, plasma glucose, insulin, cholesterol, triglycerides and creatinine in rats with fructose-induced hypertension. Male Wistar rats in groups of 6 animals each were fed fructose-rich diets or standard chow for 3 weeks and treated with 100 mg/kg/day or 200 mg/kg/day of plant extract or vehicle for 3 subsequent weeks. Systolic blood pressure was measured every three days using the indirect tail cuff method. Systolic blood pressure was higher in fructose-fed rats (142+/-2 mm Hg, p < 0.01) compared with the controls (112+/-2 mm Hg), and was lower in Dorstenia psilurus-treated groups (127+/-2 and 119+/-1 mm Hg for the dose of 100 and 200 mg/kg, respectively) compared with the fructose-fed rats. Plasma insulin, cholesterol and triglycerides were higher on the fructose-rich diet compared with the controls. Plasma insulin and cholesterol were lower in the Dorstenia psilurus-treated groups. These results suggest that, Dorstenia psilurus treatment could prevent and reverse high blood pressure induced by a diet rich in fructose probably by improvement of plasma insulin levels. The plant extract might prove useful in the treatment and/or prevention of hypertension.

In vitro purgative effect of Ruellia praetermissa. Sceinf.ex.Lindau (Acanthaceae).

Methanol, ethylacetate and aqueous extracts of Ruellia praetermissa initiated spontaneous contractions in the quiescent and increased contraction on the electrically stimulated ileal strip at a concentration of 30 microg/ml. The extracts produced concentration-related contractions both in amplitude and tone up till 750 microg/ml with IC(50) of 360 microg/ml (methanol extract), 425 microg/ml (ethylacetate extract) and 540 microg/ml (aqueous extract). Acetylcholine also produced a concentration-related (IC(50)=18 microg/ml) contractions of the isolated ileum. Atropine in concentrations of 3.4 x 10(-6)-3 x 10(-3) microg/ml antagonized progressively the response of the isolated ileum to acetylcholine (32 x 10(-2) microg/ml) and the methanol extract (650 microg/ml) induced contractions suggesting a mode of action via cholinergic system. Luteolin and apigenin and iridoid glucosides (taxiphilin and 8-epi-deoyganic acid) might be responsible at least in part for the observed effect.