The anticonvulsant and sedative effects of Gladiolus dalenii extracts in mice.

Gladiolus dalenii Van Geel is a medicinal plant commonly used in traditional medicine in Africa to treat epilepsy and many other diseases. Two in vivo mouse models (maximal electroshock and pentylenetetrazol-induced convulsions) were used to evaluate the anticonvulsant activities of the plant extracts. Diazepam-induced sleep was used for the evaluation of the sedative properties. The macerated extract of G. dalenii protected 100 and 83.3% of mice against PTZ- and MES-induced seizures, respectively. The aqueous extract of G. dalenii protected 100 and 83.3% of mice against PTZ- and MES-induced seizures, respectively. The lyophilized extract of G. dalenii also protected 100 and 83.3% of mice against PTZ- and MES-induced seizures, respectively. The coadministration of G. dalenii with diazepam resulted in an additive effect, while the coadministration of G. dalenii with flumazenil or FG7142 resulted in antagonistic effects. The macerate of G. dalenii also exerted sedative activity by reducing the latency time to sleep and increasing the total duration of sleep induced by diazepam. The sleeping time increased from 16±3min in the control group to 118±11min at a dose of 150mg/kg of G. dalenii. The effects of G. dalenii suggested the presence of anticonvulsant and sedative activities that might show efficacy against secondarily generalized tonic-clonic seizures and primary generalized seizures and insomnia in humans.

Decoctions of Bridelia micrantha and Croton macrostachyus may have anticonvulsant and sedative effects.

Bridelia micrantha and Croton macrostachyus are medicinal plants used empirically in traditional medicine to treat epilepsy. In vivo mice model (maximal electroshock, strychnine, pentylenetetrazol, picrotoxin, isonicotinic hydrazide acid)-induced convulsions were used to evaluate the anticonvulsant activities of those plants. Diazepam-induced sleep was used for the evaluation of the sedative properties. B. micrantha protected 100, 80, 80, and 80% of mice against PIC, STR, PTZ and MES-induced seizures, respectively. C. macrostachyus at the doses 34 and 67 mg/kg protected 80, 80, 80 and 60% of mice from PIC, STR, PTZ and MES-induced seizures, respectively. B. micrantha and C. macrostachyus also delayed the onset to seizures in INH test. B. micrantha was more potent than C. macrostachyus in protecting mice against convulsions. The co-administration of the sub effective dose of the decoction of B. micrantha or C. macrostachyus with the sub effective dose of diazepam or clonazepam resulted in a synergistic effect. The decoctions of B. micrantha and C. macrostachyus also exerted sedative activity by increasing the total duration of sleep induced by diazepam and by reducing the latency time to sleep. The effect of the decoctions of B. micrantha and C. macrostachyus suggests the presence of anticonvulsant activities that might show efficacy against secondarily generalized tonic-clonic seizures and primary generalized seizures in humans.

Anxiolytic activity evaluation of four medicinal plants from Cameroon.

Afrormosia laxiflora (A. laxiflora), Chenopodium ambrosioides (C. ambrosioides), Microglossa pyrifolia (M. pyrifolia) and Mimosa pudica (M. pudica) are plants used in traditional medicine in Cameroon to treat insomnia, epilepsy, anxiety, and agitation. They were evaluated for their anxiolytic like activity in mice. Animal models (elevated plus maze and stress-induced hyperthermia tests) were used. The four plants showed anxiolytic activity. In stress-induced hyperthermia test, A. laxiflora, C. ambrosioides, M. pyrifolia and M. pudica significantly antagonised the increase of temperature. ΔT° decreased from 0.75°C in the control group to 0.36°C at the dose of 110 mg/kg for A. laxiflora; from 1°C in the control group to -1.1°C at the dose of 120 mg/kg for C. ambrosioides; from 1.7°C in the control group to 0.2°C at the dose of 128 mg/kg for M. pyrifolia and from 1.3°C in the control group to 0.5°C at the dose of 180 mg/kg for M. pudica. In the elevated plus maze test, the four plants increased the number of entries into, percentage of entries into, and percentage of time in open arms. A. laxiflora, C. ambrosioides and M. pudica also reduced the percentage of entries and time in closed arms. In addition, C. ambrosioides, M. pyrifolia and M. pudica showed antipyretic activity by reducing the body temperature. The results suggested that C. ambrosioides, M. pyrifolia and M. pudica posses anxiolytic-like and antipyretic activities while A. laxiflora possesses only anxiolytic-like properties. These plants could be helpful in the treatment of anxiety and fever in traditional medicine in Cameroon.

Anticonvulsant, anxiolytic, and sedative properties of the roots of Nauclea latifolia Smith in mice.

Root bark of Nauclea latifolia Smith (Rubiaceae) was evaluated for its anticonvulsant, anxiolytic, and sedative activity in mice. Animal models (maximal electroshock-, pentylenetetrazol-, and strychnine-induced convulsions; N-methyl-D-aspartate-induced turning behavior; elevated plus maze; stress-induced hyperthermia; open field; and diazepam-induced sleep) were used. The decoction from the bark of the roots of N. latifolia strongly increased the total sleep time induced by diazepam. It also protected mice against maximal electroshock-, pentylenetetrazol-, and strychnine-induced seizures. In addition, turning behavior induced by N-methyl-D-aspartate was inhibited. N. latifolia antagonized, in a dose-dependent manner, stress-induced hyperthermia and reduced body temperature. In the elevated plus maze, N. latifolia increased the number of entries into, percentage of entries into, and percentage of time in open arms, and reduced rearing, head dipping, and percentage of time in closed arms. In the open field test, N. latifolia increased crossing and reduced rearing and defecation. It could be concluded that the decoction of N. latifolia, used in traditional medicine in Cameroon in the treatment of fever, malaria, insomnia, anxiety and epilepsy seemed to possess, sedative, anticonvulsant, anxiolytic and antipyretic properties in mice.

Validation of anticonvulsant and sedative activity of six medicinal plants.

Acanthus montanus, Alchornea laxiflora, Hyptis spicigera, Microglossa pyrifolia, Piliostigma reticulatum, and Voacanga africana were evaluated with respect to anticonvulsant and sedative activity in mice using animal models (maximal electroshock (MES), N-methyl-D-aspartate (NMDA), pentylenetetrazol (PTZ), isonicotinic hydrazide acid (INH), picrotoxin (PIC), and strychnine (STR)-induced convulsions or turning behavior and diazepam-induced sleep). Acanthus montanus protected 66.6% of mice against MES-, PIC-, and STR-induced convulsions and 83.3% of mice from PTZ-induced convulsions. Alchornea laxiflora protected 75% and 87.5% of mice in the STR and NMDA tests, respectively, at a dose of 120 mg/kg. Hyptis spicigera protected 100 and 87.5% of mice against STR- and PTZ-induced convulsions, respectively, at a dose of 160 mg/kg. Microglossa pyrifolia protected 50% to 100% of mice against convulsions. Piliostigma reticulatum protected 62.5% to 100% of mice against convulsions and turning behavior. Voacanga africana protected 62.5% to 87.5% of mice against convulsions and turning behavior. All of the plants except A. laxiflora also exerted sedative activity by strongly increasing the total duration of sleep induced by diazepam.

Methanol extract of Terminalia superba induces endothelium-independent relaxation of rat thoracic aorta.

Terminalia superba is highly regarded in some parts of Cameroon in traditional medical practice. We have studied the vasorelaxant effects of the stem bark methanol extract of T. superba on rat vascular smooth muscle. The results demonstrated that T. superba extract provoked a time-dependent relaxation of aortic rings precontracted with norepinephrine (10(-6) M). The vasorelaxant effect of the plant extract was not affected by endothelium removal or by pretreatment with indomethacin or N(W)-nitro-Larginine methyl ester (L-NAME). T. superba extract did not significantly, affect the contraction induced by 30 mM or 60 mM KCl as compared to those induced by NE. Relaxations elicited by T. superba extract were markedly reduced by glibenclamide, a putative blocker for K(ATP) channels and by tetraethylammonium, the non-specific K+ channel inhibitor. T. superba caused a time- and concentration-dependent relaxation of the rat aortic rings that were inhibited by charybdotoxin and iberotoxin but not by apamin. These finding indicate that T. superba extract at least partially relaxes the rat aorta by activating K+ channels, mainly KATP channels and large-conductance Ca2+ -activated K+ channels in rat aorta.

Relaxant effects of the neutral extract of the leaves of Bidens pilosa Linn on isolated rat vascular smooth muscle.

The long-lasting antihypertensive effect of a neutral extract of Bidens pilosa has been suggested to be due to vasodilation. The present work was undertaken to assess this hypothesis. The vasorelaxant effect of a neutral extract (NBp) of the leaves of B. pilosa was evaluated in vitro on isolated rat aorta contracted with KCl or norepinephrine. NBp induced a concentration-dependent vasorelaxation of the rat aorta precontracted with KCl (60 mM) by 25%-105% at the respective concentrations of 0.25-1.5 mg/mL. The maximal concentration of 1.5 mg/mL provoked 88% relaxation of norepinephrine-induced contractions. There were no significant differences between the effects of the extract on the aorta strips with or without endothelium. In the presence of indomethacin or pyrilamine maleate, the relaxant response induced by the plant extract was significantly inhibited at the lower concentrations. The plant extract was able to reduce the aorta resting tone, inhibit the KCl-induced contractions (90% at 1.5 mg/mL) and the CaCl2-induced contractions by 95% at a concentration of 0.75 mg/mL. These results demonstrate the vasodilating properties of the neutral extract of Bidens pilosa and indicate that it may act as a calcium antagonist.

Ions and amino acid analysis of Cyperus articulatus L. (Cyperaceae) extracts and the effects of the latter on oocytes expressing some receptors.

Extracts from rhizomes of Cyperus articulatus L. (Cyperaceae) used in Africa and Amazonia to treat many diseases has been shown to possess sedative and anticonvulsant properties. The aim of this study is to determine the mechanism of action of Cyperus articulatus extracts. In Xenopus oocytes expressing receptors, using electrophysiological measurement, extracts of rhizomes of Cyperus articulatus (300 microg/ml) inhibited 50% of the EC(50) and EC(80) of glutamate (1.3 and 2.9 microM, respectively) induced inward current through hNMDAR1A/2A receptors. Extracts induced very small current through rGluR3 receptors. The largest current induced by the extract (30 mg/ml) represents 128% of the EC(100) of glutamate induced inward current, through rGluR3 receptors. The excess 28% current could be induced by aspartate and/or glutamate in the extracts. The effect on Xenopus oocytes expressing heteromeric GABA(B)R1b/R2 receptors and rectifying potassium channels (Kir3) is clear. A decoction and water extract of Cyperus articulatus induced a large inward current that represented 71 and 57% (respectively) of the EC(100) of gaba (30 microM) induced inward current. The water extract induced also a large current through rectifying potassium channels (Kir3). Part of the current induced through GABA(B) receptors could be related to rectifying potassium channels and GABA(B) site receptors. Cyperus articulatus extracts possessed components that could decrease excitation (NMDA receptor antagonists) and increase inhibition (GABA(B) receptor agonists) in the central nervous system.

Anticonvulsant activity of Mimosa pudica decoction.

The decoction of Mimosa pudica leaves given intraperitoneally at dose of 1000-4000 mg/kg protected mice against pentylentetrazol and strychnine-induced seizures. M. pudica had no effect against picrotoxin-induced seizures It also antagonized N-methyl-D-aspartate- induced turning behavior. These properties could explain its use in African traditional medicine.

Possible mechanisms of action of the neutral extract from Bidens pilosa L. leaves on the cardiovascular system of anaesthetized rats.

The aim of this study was to investigate the hypotensive and cardiac effects of the neutral extract from Bidens pilosa leaves. Intravenous administration of the extract resulted in a biphasic dose-related hypotensive activity. In normotensive rats (NTR), B. pilosa decreased systolic blood pressure by 18.26%, 42.5% and 30% at doses of 10, 20 and 30 mg/kg, respectively. In spontaneously hypertensive rats (SHR), the decrease in systolic blood pressure was 25.77%, 38.96% and 28.64% at the above doses, respectively. These doses induced hypotension by 27%, 34.13% and 18.73% respectively in salt-loaded hypertensive rats. In NTR, B. pilosa reduced heart rate by 23.68% and 61.18% at doses of 20 and 30 mg/kg, respectively. The force of contraction of the heart was only affected at 30 mg/kg. The initial phase of hypotensive response was partially inhibited by atropine while propranolol increased this effect. These results suggest that B. pilosa exhibited its fi rst hypotensive effects by acting on the cardiac pump efficiency and secondly through vasodilation.

Effects of Cyperus articulatus compared to effects of anticonvulsant compounds on the cortical wedge.

Cyperus articulatus L. (Cyperaceae) is a plant commonly used in traditional medicine in Africa and Latin America to treat many diseases. The water extract from rhizomes of Cyperus articulatus concentration-dependently reduced spontaneous epileptiform discharges and NMDA-induced depolarisations in the rat cortical wedge preparation at concentrations at which AMPA-induced depolarisations are not affected. The two antiepileptic compounds, valproate and ethosuximide, possessed effect neither on epileptiform discharges nor on AMPA- and NMDA-induced depolarisations. Phenobarbital, pentobarbital and phenythoin inhibited both AMPA- and NMDA-induced depolarisations and spontaneous epileptiform discharges. The effects of Cyperus articulatus were very close to the effect of D-CPPene. D-CPPene also inhibited spontaneous epileptiform discharges and antagonised NMDA- but not AMPA-induced depolarisations. The extract of Cyperus articulatus could contain components acting as NMDA antagonists.

In vitro vascular smooth muscle contractile activity of Aspilia africana extract on rat aortic preparations.

Aspilia africana is widely used in ethnomedical practice in Africa for its ability to stop bleeding, even from a severed artery, as well as promote rapid healing of wounds and sores, and for the management of problems related to cardiovascular diseases. In the present paper, the methylene chloride/methanol extract of A. africana leaves was tested for its contractile activity in vitro. Rings of rat aorta, with or without an intact endothelium, were mounted in tissue baths, contracted with norepinephrine, and then exposed to the plant extract. The effect of the extract was also assessed on the baseline tension of aortic rings in normal and calcium-free PSS. At the lower doses, A. africana slowly re-inforced contractions induced by norepinephrine and relaxed precontracted tension at the highest concentration. The relaxant activity of the extract was endothelium-independent and was not modified by pre-treatment with Nw-nitro-L-arginine methyl ester or indomethacin, suggesting that its effect was not mediated by either nitric oxide or prostacyclin. A. africana extract induced slow and progressive increase in the basal vascular tone which was partially endothelium-dependent. In calcium-free PSS, a high proportion of the contractile activity was inhibited (77%), suggesting that A. africana contractile activity in vascular tissue depends, in part, on extracellular calcium.

Anticonvulsant properties of the methanolic extract of Cyperus articulatus (Cyperaceae).

The methanolic extract of rhizomes of Cyperus articulatus, a plant used in traditional medicine in Africa and Latin America for many diseases, possesses anticonvulsant activity in mice. This extract protected mice against maximal electroshock (MES)- and pentylenetetrazol (PTZ)-induced seizures. It also delayed the onset of seizures induced by isonicotinic acid hydrazide and strongly antagonized N-methyl-D-aspartate-induced turning behavior. The ED(50) for protection against seizures was 306 (154-541) mg/kg intraperitoneally (i.p.) for the PTZ test and 1005 (797-1200) mg/kg i.p. for the MES test. The ED(50) of methanolic extract against N-methyl-D-aspartate-induced turning behavior was 875 (623-1123) mg/kg i.p. C. articulatus L. methanolic extract protected 54% of mice from seizures induced by strychnine at the dose of 1000 mg/kg i.p. but had no or a moderate effect only against picrotoxin- or bicuculline-induced seizures. With these effects, the rhizome of C. articulatus L. possesses anticonvulsant properties in animals that might explain its use as a traditional medicine for epilepsy in Africa.

[Hypotensive effects of a methanol extract of Bidens pilosa Linn on hypertensive rats]. / Effets hypotensifs de l'extrait au méthanol de Bidens pilosa Linn chez les rats hypertendus.

Bidens pilosa Linn is highly regarded in some parts of Cameroon in traditional folk medical practices. The hypotensive effects of the leaf methanol extract from Bidens pilosa Linn (Asteraceae) were evaluated in spontaneously hypertensive rats (SHR), salt-loading hypertensive rats (SLHR) and normotensive Wistar rats (NTR) using the indirect (tail-cuff) method. Acute changes in urine volume and urinary excretion of Na+ and K+ were also studied. The hypotensive effect of the extract was more remarkable in hypertensive than in normotensive rats. Bidens pilosa did not provoke significant changes in the heart rate and urine volume. Urinary excretion of Na+ was decreased by 36% in spontaneously hypertensive rats and the excretion of K+ increased by 35% in normotensive rats but the effects were not statistically significant. These results suggest that the extract is a useful antihypertensive drug which has no effect on the heart frequency. The hypotensive effects of the extract may be induced by vasodilation.

Effects of leaf aqueous extract of Bidens pilosa (Asteraceae) on KCl- and norepinephrine-induced contractions of rat aorta.

The effect of leaf aqueous extract of Bidens pilosa Linn. on KCl- and norepinephrine-induced contractions of rat aortic strips was studied. In aortic strips with endothelium intact, contractions induced using 60 mM KCl and 10(-5) M norepinephrine were dose-dependently relaxed by the extract, a more significant effect being seen with norepinephrine-induced contractions. Following mechanical damage to the aortic endothelium, inhibition of contractions was more prominent (105%) with the norepinephrine-induced contractions compared with KCl-induced contractions (15%) when the maximal dose (8 mg/ml) of the extract was used. The results suggest that the relaxation effect of the extract may be due to the blockade of the influx of extracellular Ca2+ into the cell.