Télesphore Benoît Nguelefack

Acute and subchronic oral toxicity assessment of the aqueous extract from the stem bark of Erythrina senegalensis DC (Fabaceae) in rodents

AIM OF THE STUDY The decoction of the stem bark of Erythrina senegalensis (EAES) is traditionally used in the Western region of Cameroon against liver disorders. The present study evaluated the potential toxicity of this decoction after acute and sub-chronic administration in rodents. MATERIALS AND METHODS In acute study, a single administration of EAES was given orally to mice at doses ranging from 1.25 to 12.5 g/kg. General behaviour, adverse effects and mortality were determined for up to 14 days post treatment. In the sub-chronic study, EAES was given orally as a single administration to Wistar rats at doses of 300, 600 and 1,200 mg/kg/day for 28 days. Animal body weight was observed throughout the experimental period while haematological and biochemical parameters of blood and urine, as well as kidney and liver tissues histology were evaluated at the end of the experiment. RESULTS In the acute study in mice, none of the doses used induced mortality or significant behavioural changes. In the sub-chronic study in rats, daily oral administration of EAES at the dose of 600 mg/kg resulted in a significant increase in the relative body weight at the last week of treatment. The relative weights of organs were not affected by the treatment. No haematological changes were observed a part of a significant increase in WBC count at the dose of 600 mg/kg. Serum AST, ALT, ALP, total protein, total cholesterol and triglycerides decreased significantly while total and conjugated bilirubin significantly increased. Renal function indices assay in blood showed significant modification in all the treated groups compared to control while, in urine, only urea excretion markedly reduced at a dose of 1,200 mg/kg. Histological analysis did no show any liver or kidney alteration. CONCLUSION These results demonstrated that there is a wide margin of safety for the therapeutic use of EAES and further corroborated the traditional use of this extract as a hepatoprotective agent.

Arbutus unedo prevents cardiovascular and morphological alterations in L-NAME-induced hypertensive rats Part I. Cardiovascular and renal hemodynamic effects of Arbutus unedo in L-NAME-induced hypertensive rats

Hypertension induced by nitric oxide synthase inhibition is associated with functional abnormalities of the heart and kidney. The aim of the present study was to investigate whether chronic treatment with Arbutus unedo leaf (AuL) or root (AuR) aqueous extracts can prevent these alterations. Six groups of rats were used: control group received tap water; N(G)-nitro-l-arginine methyl-ester (L-NAME) group treated with L-NAME at 40 mg/kg/day; AuL and AuR groups received simultaneously L-NAME (40 mg/kg/day) and Au leaves or roots extract at the same concentration 250 mg/kg/day; l-arginine and enalapril groups received simultaneously L-NAME (40 mg/kg/day) and l-arginine at 50mg/kg/day or enalapril at 15 mg/kg/day. Treatment of rats during 4 weeks with L-NAME caused an increase of the systolic blood pressure (SBP) accompanied by a ventricular hypertrophy, an impairment of endothelium-dependent vasorelaxation, an increase of the cardiac baroreflex sensitivity and a decrease of water, sodium and potassium excretion. The co-administration of AuL or AuR extracts with L-NAME reduces the development of increased SBP, ameliorates the vascular reactivity as well as the baroreflex sensitivity and normalizes the renal function. AuR reduces the ventricular hypertrophy but AuL do not. Enalapril associated with L-NAME reverses the majority of alterations induced by L-NAME while l-arginine only lightly ameliorates the vascular reactivity. These results show that chronic treatment with Arbutus extract regress the development of hypertension and ameliorate cardiovascular and renal functions in NO deficient hypertension.

Analgesic and Anti-Inflammatory Properties of Extracts from the Bulbils of Dioscorea bulbifera L. var sativa (Dioscoreaceae) in Mice and Rats

The aqueous and methanol extracts from the dry bulbils of Dioscorea bulbifera L. var sativa (Dioscoreaceae)—evaluated orally at the doses of 300 and 600 mg/kg against pain induced by acetic acid, formalin, pressure and against inflammation induced by carrageenan, histamine, serotonin and formalin in mice and rats, showed a dose dependant inhibition of pain and inflammation with a maximum effect of 56.38%, 73.06% and 42.79% produced by the aqueous extract, respectively on pain induced by acetic acid, formalin and pressure while the methanol extract at the same dose respectively inhibited these models of pain by 62.70%, 84.54% and 47.70%. The oral administration of aqueous and methanol extracts caused significant anti-inflammatory activity on paw oedema induced by histamine, serotonin and formalin. The present results show that the bulbils of Dioscorea bulbifera var sativa possess potent analgesic and anti-inflammatory activities. These activities may results from the inhibition of inflammatory mediators such as histamine, serotonin and prostaglandins. Thus, the analgesic activity of the bulbils of Dioscorea bulbifera may be at least partially linked to its anti-inflammatory activity.

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.

Anti-ulcerogenic properties of the aqueous and methanol extracts from the leaves of Solanum torvum Swartz (Solanaceae) in rats.

ETHNOPHARMACOLOGICAL RELEVANCE Solanum torvum (Solanaceae) is a plant currently used in Cameroon ethnomedicine for the treatment of stomach ailments. AIM OF THE STUDY The present study was undertaken to determine the anti-ulcer potential of the aqueous and methanol extracts from the leaves of Solanum torvum. MATERIALS AND METHODS The aqueous and methanol extracts from the leaves of Solanum torvum were tested orally at the doses of 250, 500 and 750 mg/kg, on gastric ulcerations experimentally induced by HCl/ethanol, indomethacin, pylorus ligation and stress. The fractionation of the methanol extract through silica gel column chromatography produced seven different fractions (A-G) which were tested orally at the dose of 100mg/kg against HCl/ethanol-induced ulceration. RESULTS The methanol extract at the dose of 750 mg/kg produced 98.12, 99.16, 98.70 and 96.03% inhibition when gastric ulcerations were induced by HCl/ethanol, indomethacin, pylorus ligation and stress, respectively. The aqueous extract at the same dose produced 96.55, 96.86, 98.63 and 98.63% inhibition on ulcerations induced respectively by HCl/ethanol, indomethacin, pylorus ligation and stress. All the fractions of the methanol extract significantly inhibited ulcer formation. Fraction F which contains flavonoids and triterpens was the most active and exhibited an inhibitory percentage of 84.74. Both extracts significantly increased mucus production and reduced gastric acid secretion. CONCLUSIONS The aqueous and methanol extracts of the leaves of Solanum turvum possess anti-ulcerogenic properties that may be due to cytoprotective mechanism. These results support the ethnomedical uses of the plant in the treatment of gastric ulcer.

Anti-inflammatory and Analgesic Effects of Drypemolundein A, a Sesquiterpene Lactone from Drypetes molunduana

Previous pharmacological screening in our laboratory showed analgesic and anti-inflammatory effects of a crude stem bark extract of Drypetes molunduana. Phytochemical studies of this plant led to the isolation an structural elucidation of seven pentacylic triterpenes and one lignan, which were already known compounds, and a new furanosesquiterpene lactone, Drypemolundein A. The purpose of this study was to examine the anti-inflammatory and analgesic activities of drypemolundein A. The compound was studied against carrageenan-induced acute edema. At doses of 10 and 20 mg/kg, orally administered, it significantly reduced (57.57 and 66.66% inhibition at 1 h intervals, respectively) paw edema. At the same doses, this sesquiterpene lactone also exhibited significant analgesic action in force-induced pain in rat paw. These results indicate that drypemolundein A functions as an effective anti-inflammatory and analgesic agent.

Antinociceptive activities of the methanol extract of the bulbs of Dioscorea bulbifera L. var sativa in mice is dependent of NO-cGMP-ATP-sensitive-K+ channel activation.

ETHNOPHARMACOLOGICAL RELEVANCE Dioscorea bulbifera var sativa is a medicinal plant commonly used in Cameroonian traditional medicine to treat pain and inflammation. AIM The present work evaluated the effects of the methanol extract of the bulbs of Dioscorea bulbifera in inflammatory and neuropathic models of pain and further investigated its possible mechanism of action. MATERIALS AND METHODS The effects of Dioscorea bulbifera administered orally at the doses of 250 and 500mg/kg were tested in mechanical hypernociception induced by intraplantar (i.pl.) injection of complete Freunds adjuvant (CFA), lipopolysaccharides (LPS) or prostaglandin-E(2) (PGE(2)), as well as in partial ligation sciatic nerve (PLSN), nociception induced by capsaicin and thermal hyperalgesia induced by i.pl. injection of CFA. The therapeutic effects of Dioscorea bulbifera on PGE(2)-induced hyperalgesia were evaluated in the absence and in the presence of l-NAME, an inhibitor of nitric oxide synthase (NOS) and glibenclamide, an inhibitor of ATP-sensitive potassium channels. RESULTS The extract showed significant antinociceptive effects in persistent pain induced by CFA and on neuropathic pain induced by PLSN. The effects of Dioscorea bulbifera persisted for 5 days after two administrations in CFA-induced hypernociception. Dioscorea bulbifera significantly inhibited acute LPS-induced pain but failed to reduce thermal hypernociception and capsaicin-induced spontaneous nociception. The antinociceptive effects of this plant extract in PGE(2) model was antagonized by either l-NAME or glibenclamide. CONCLUSION Present demonstrate the antinociceptive activities of Dioscorea bulbifera both in inflammatory and neuropathic models of pain and these effects may result, at least partially, from its ability to activate the NO-cGMP-ATP-sensitive potassium channels pathway.

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.

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 animals 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-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.