Inhibitory effects of quercetin on guinea-pig ileum contractions

The inhibitory effect of quercetin on the guinea-pig ileum contractile responses was examined to further clarify its mechanism of action. Quercetin inhibited, from doses of 5 μM , the spontaneous phasic contractions of the guinea-pig ileum, as well as the phasic and tonic components of either acetylcholine- or KCl-elicited contractions, in a dose-dependent way. The former effect was reversible and was unaffected by nicotinic blockade. The tonic component of the contractions was more responsive to quercetin than the phasic component. The inhibition of the tonic contraction was, at least partially, due to the blockade of calcium channels by quercetin, since increasing calcium concentration in the tissue bath reversed the inhibition when the organ was contracted by KCl. Quercetin may also interfere with calcium release from intracellular stores, since it inhibited acetylcholine-elicited phasic contraction even in a calcium-free solution. Finally, quercetin shifted the concentration-response curves to carbachol downwards, without modifying the ED₅₀ of the agonist, whereas the concentration-response curves to CaCl₂ were shifted downwards and to the right. In conclusion, quercetin inhibits the contractile responses of guinea-pig ileum, decreasing the calcium concentration available for contractile machinery.     

Calcium antagonistic activity of Bacopa monniera on vascular and intestinal smooth muscles of rabbit and guinea-pig.

The present study demonstrates the calcium antagonistic activity in ethanol extract of Bacopa monniera. The plant extract inhibited the spontaneous movements of both guinea-pig ileum (IC50 = 24+/-4 microg/ml) and rabbit jejunum (IC50 = 136+/-9 microg/ml). A marked reduction in acetylcholine- and histamine-induced responses (0.0001-10 microM) in the ileum was evident in the presence of extract (260 microg/ml). The acetylcholine (1 microM)-induced contraction in the ileum was also inhibited by the extract (100-700 microg/ml) in a concentration dependent way (IC50 = 285+/-56 microg/ml). All these results indicate a direct action of the extract on smooth muscles. Calcium chloride-induced responses in the rabbit blood vessels and jejunum were attenuated in the presence of plant extract (10-700 microg/ml) implying a direct interference of plant extract with influx of calcium ions in the cells. However, the lack of modification of either noradrenaline- or caffeine-induced contractions in the presence of extract suggests that extract has no detectable effect on mobilization of intracellular calcium. These results indicate that spasmolytic effect of the B. monniera extract in smooth muscles is predominantly due to inhibition of calcium influx via both voltage and receptor operated calcium channels of the cell membrane.     

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.     

Antispasmodic and hypotensive effects of Ferula asafoetida gum extract

The effects of Ferula asafoetida gum extract on the contractile responses of the isolated guinea-pig ileum induced by acetylcholine, histamine and KCl, and on the mean arterial blood pressure of rat were investigated. In the presence of extract (3 mg/ml), the average amplitude of spontaneous contractions of the isolated guinea-pig ileum was decreased to 54 +/- 7% of control. Exposure of the precontracted ileum by acetylcholine (10 microM) to Ferula asafoetida gum extract caused relaxation in a concentration-dependent manner. Similar relaxatory effect of the extract was observed on the precontracted ileum by histamine (10 microM) and KCl (28 mM). However, when the preparations were preincubated with indomethacin (100 nM) and different antagonists, such as propranolol (1 microM), atropine (100 nM), chlorpheniramine (25 nM) then were contracted with KCl, exposure to the extract (3 mg/ml) did not cause any relaxation. Furthermore, Ferula asafoetida gum extract (0.3-2.2 mg/100g body weight) significantly reduced the mean arterial blood pressure in anaesthetised rats. It might be concluded that the relaxant compounds in Ferula asafoetida gum extract interfere with a variety of muscarinic, adrenergic and histaminic receptor activities or with the mobilisation of calcium ions required for smooth muscle contraction non-specificly.     

Alcoholic extract of 'Bacopa monniera' reduces the in vitro effects of morphine withdrawal in guinea-pig ileum

The effect of the alcoholic extract of the whole plant of Bacopa monniera (Scrophulariaceae) on morphine withdrawal was evaluated in vitro in guinea-pig ileum. After a 4 min in vitro exposure to morphine, addition of naloxone induced a strong contraction. Addition of various concentrations of the alcoholic extract of B. monniera (100-1000 microg/ml) 15 min before exposure to morphine reduced the naloxone-induced contraction in a dose-dependent manner. The results suggest that B. monniera extract may be useful in reducing the withdrawal symptoms induced by morphine.     

The pharmacological properties of the ethanolic root extract of Combretum dolichopetalum

The pharmacological actions of the crude ethanolic extract and the active fractions of the roots of Combretum dolichopetalum were tested on guinea-pig isolated ileum and in intact rats. The extract relaxed guinea-pig ileum in a concentration-dependent manner. Two active fractions (R_f 0.96 and 0.84) which also relaxed the guinea-pig ileum were isolated using column chromatography and TLC respectively. Both the crude extract and the active fractions inhibited the contractions induced by acetylcholine and histamine concentration-dependently in the guinea-pig ileum. The crude extract inhibited ulcers and gastric secretions induced in rats by pyloric ligation together with histamine 100 mg/kg, i.p. (p<0.05). The extract also delayed gastric emptying in rats in a dose-dependent manner. The effects of the extract were compared with cimetidine at each stage of the study.     

Effect of Extract of Leaf and Seed of Piper guineense on Some Smooth Muscle Activity in Rat,Guinea-pig and Rabbit

Extracts of the leaf and seed of Piper guineense were separately prepared and their pharmacological effects screened using smooth muscle of the gastrointestinal tract and uterus. The leaf extract enhanced both the frequency and tone of spontaneous contractions of rabbit jejunum and induced contraction of guinea-pig ileum, which were blocked by atropine. The seed extract had the opposite effect on rabbit jejunum, an inhibition which was antagonized by prazocin, and little or no effect on guinea-pig ileum. Both extracts had a stimulant effect on rat uterine muscle, the seed extract to a lesser extent.     

Flavonoids as antagonists at A1 adenosine receptors

This study aimed to investigate the potential for flavonoid action at A(1) adenosine receptors in vitro. In a radioligand binding assay for A(1) adenosine receptor occupancy in particulate preparations from guinea-pig cerebral cortex, flavonoids competed in concentration-dependent manners with Hill slopes typically not different from unity. Of the flavonoids tested, quercetin showed highest affinity (pKi value of 5.33). At a concentration of 28 mm, quercetin evoked a rightward shift in the N(6)-cyclopentyladenosine-induced inhibition of electrically evoked contractions of the guinea-pig isolated ileum, allowing the calculation of a pK(i) value of 4.71. These data suggest, therefore, that flavonoids represent an additional dietary source of A(1) adenosine receptor antagonists (beyond the methylxanthines, caffeine and theophylline).     

Antidiarrhoeal effects of Ocimum gratissimum leaf extract in experimental animals

The aqueous extract of the leaves of Ocimum gratissimum was screened for antidiarrhoeal effects. The extract inhibited castor oil-induced diarrhoea in rats as judged by a decrease in the number of wet faeces in the extract-treated rats. In addition, the extract inhibited the propulsive movement of intestinal contents. On the isolated ileum of guinea-pig, the extract showed no direct action; however, it reduced the responses of the guinea-pig ileum to acetylcholine, nicotine and histamine. Phytochemical tests revealed the main constituents as tannins, steroids, triterpenoid and carbohydrates. These findings suggested that the aqueous extract of the leaves of O. gratissimum might elicit an antidiarrhoeal effect by inhibiting intestinal motility, partly via muscarinic receptor inhibition.     

Relaxant activity of raspberry (Rubus idaeus) leaf extract in guinea-pig ileum in vitro

Tea made from the leaves of Rubus idaeus L. (raspberry) has been used for centuries as a folk medicine to treat wounds, diarrhoea, colic pain and as a uterine relaxant. Extracts of dried raspberry leaves prepared with different solvents, (n-hexane, ethyl acetate, chloroform and methanol) were tested in vitro for relaxant activity on transmurally stimulated guinea-pig ileum. The methanol (MeOH) extract exhibited the largest response and also indicated that the active compounds are of a relatively polar nature. Hence the bulk of the leaves were extracted with methanol and the dried extract fractionated on a silica gel column, eluting with chloroform, mixtures of chloroform and methanol and finally methanol. Each fraction was examined by thin layer chromatography and tested for relaxant activity in an in vitro transmurally stimulated guinea-pig ileum preparation. The fractions eluted with chloroform (CHCl(3)) lacked relaxant activity. Samples eluted with CHCl(3)/MeOH (95:5) had moderate relaxant activity, while a second distinctive peak of activity eluted with a more polar solvent mixture (CHCl(3)/MeOH 50:50) provided strong dose dependent responses. Evidence was obtained that there are at least two components of raspberry leaf extract which exhibit relaxant activity in an in vitro gastrointestinal preparation.     

Pharmacological basis for the gut stimulatory activity of Raphanus sativus leaves

The crude extract of Raphanus sativus leaves (Rl.Cr) showed a dose-dependent (0.03-5.0 mg/ml) spasmogenicity in guinea-pig ileum and colon. The effect was insensitive to atropine pre-treatment but was completely abolished by pyrilamine indicating involvement of histaminergic (H(1)) receptors. The contractile effect at high doses (3.0-5.0mg/ml) was followed by relaxation. Rl.Cr also enhanced the transit of charcoal meal in mice at 30-100 mg/kg. The petroleum spirit, chloroform and aqueous fractions all showed histaminergic activity in ileum; aqueous fraction being more potent. The study shows the presence of a histaminergic component(s) along with a weak spasmolytic factor thus providing sound mechanistic basis for the traditional use of the plant in constipation.     

Effects of Crocus sativus petals' extract on rat blood pressure and on responses induced by electrical field stimulation in the rat isolated vas deferens and guinea-pig ileum

We have investigated the effects of Crocus sativus petals' extract on blood pressure in anaesthetised rats and also on responses of the isolated rat vas deferens and guinea-pig ileum induced by electrical field stimulation (EFS). Aqueous and ethanol extracts of C. sativus petals reduced the blood pressure in a dose-dependent manner. For example administration of 50 mg/100 g of aqueous extract changed the blood pressure from 133.5+/-3.9 to 117+/-2.1 (mmHg). EFS of the isolated rat vas deferens and guinea-pig ileum evoked contractions were decreased by aqueous and ethanol extracts of C. sativus petals. The aqueous extract (560 mg/ml) significantly reduced the contractile responses of vas deferens to epinephrine (1 microM) without any change in contraction induced by KCl (300 mM). The present results may suggest that the relaxatory action of C. sativus petals' extract on contraction induced by EFS in the rat isolated vas deferens is a postsynaptic effect.     

Evaluation of pharmacological activity of a crude hydroalcoholic extract from Jatropha elliptica

The pharmacological effect of the hydroalcoholic extract of Jatropha elliptica was analysed in in vivo and in vitro models. When given orally in mice, the extract showed a low acute toxicity (LD₅₀ 5 g/kg). In a dose of 0.5 or 1 g/kg p.o. the extract did not interfere with diuresis in the rat, but was found to be effective in blocking rat paw oedema induced by carrageenan and partially, serotonin-induced oedema. In the same dose, the extract failed to inhibit rat paw oedema induced by dextran and the increase of rat cutaneous vascular permeability caused by Bothrops Jararaca venom, dextran, histamine, PAF-acether and serotonin. Pre-incubation of the isolated rat uterus and guinea-pig ileum with the extract (0.2–0.8 mg/mL), produced a concentration-related and non-competitive inhibition of contractions induced by acetylcholine and bradykinin. However, the extract was about 2-fold more potent in inhibiting the contraction of both agonists in guinea-pig ileum than in rat uterine muscle. In rat aorta, the extract (50–100 μg/mL) caused a concentration-dependent inhibition of noradrenaline-evoked contractions, being about 5-fold more potent when compared to the IC₅₀ values obtained in rat uterus.     

Antihistaminic and mast cell stabilizing activity of Striga orobanchioides

The ethanolic and aqueous extracts of the whole plant of S. orobanchioides were evaluated for antihistaminic and mast cell stabilizing activities. Both extracts inhibited histamine-induced contractions of the guinea-pig ileum at the concentration range of 2.5-25 microg/ml in a dose-related manner. At 25 microg/ml, both extracts inhibited the response of histamine (0.5 microg/ml) almost completely. The effect of these two extracts on the degranulation rate of sensitized peritoneal cells of albino rats when challenged with antigen (horse serum) was studied. Triple vaccine was used as adjuvant. Ketotifen and prednisolone were used for comparison. The ethanolic extract at 100 and 200 mg/kg body weight was found to significantly inhibit degranulation of mast cells to an extent of 52.14+/-3.24 and 67.96+/-3.70%, respectively. At the same doses, the aqueous extract showed 42.09+/-2.91 and 60.67+/-3.50% reduction in degranulation of mast cells, respectively. Hence, both extracts markedly protected the rats against antigen-induced challenge of mast cells.     

Experimental evaluation of Myracrodruon urundeuva bark extract for antidiarrhoeal activity

The bark of M. urundeuva (Anacardiaceae) used in popular medicine as an antidiarrhoeal agent has been investigated for its effects on castor oil-induced diarrhoea and on intestinal motility. In rats, the ethanol extract of stem bark significantly inhibited the castor oil-induced diarrhoea, small intestinal transit and accumulation of fluid volume at an oral dose of 400 mg/kg. Furthermore, the plant extract caused marked inhibition of the contractile responses evoked by acetylcholine and histamine on guinea-pig ileum in vitro. These results point to a possible antidiarrhoeic effect of M. urundeuva bark extract since inhibition of intestinal motility and secretion can greatly control clinical diarrhoea. Copyright © 1998 John Wiley & Sons, Ltd.     

Pharmacological basis for the use of the antivenene water soluble extract of Diodia scandens as a laxative, oxytocic agent and a possible aphrodisiac in traditional medicine practice in eastern nigeria.

The effects of the antivenene fraction of an ethanol extract of Diodia scandens on some mammalian smooth muscles were investigated. On the guinea-pig ileum, the extract was shown to be a partial agonist acting via muscarinic receptors. Acetylcholine (ACh) was 2.5 x 10(5) times more potent. On the pregnant guinea-pig uterus, the extract induced concentration-dependent increases in the force of contraction and tonus. Oxytocin and ergometrine were respectively 10(6) and 10(3) times more potent. The extract, at subliminal concentrations, potentiated ACh and adrenaline-induced contractions in the guinea-pig was deferens. It also induced dose-related vasodilatation in the rat hindquarters and depressed the blood pressure in the anaesthetized cat. It was concluded that these pharmacological actions offer some scientific explanation for the use of Diodia scandens in traditional medicine as a laxative and as an oxytocic agent. It is suggested that the extract could enhance erection and ejaculatory processes in the male, thus accounting for its regular use by some elderly males.     

Constituents of Croton menthodorus and their effects on electrically induced contractions of the guinea-pig isolated ileum

The present study examines the effects of the extracts [petroleum ether, CHCl(3), CHCl(3)MeOH (9:1) and MeOH], partially purified fractions and pure compounds from Croton menthodorus on the electrically induced contractions of the isolated guinea-pig ileum (ECI). The results of the experiments indicate that CHCl(3)/MeOH (9:1) and MeOH extracts, tested at concentrations of 100, 50 and 25 microg/mL, dose-dependently reduced the guinea-pig ileum contractions, whereas petroleum ether and CHCl(3) extracts did not affect it. Furthermore, the partially purified fractions III-VI from the CHCl(3)/MeOH extract, each tested at concentrations of 100, 50 and 25 microg/mL also inhibited ECI. Finally, pure compound 1 (6 x 10(-6), 3 x 10(-6), 1 x 10(-6) M) isolated and purified from the most active fraction III significantly reduced, in a dose-dependent manner, the electrical contractions of the ileum. Compound 1 was identified by NMR and EI-MS data as the morphinandien-7-one, O-methylflavinantine.     

Toxicological evaluation of Nerium oleander on isolated preparations

In vitro toxicological evaluation of Nerium oleander was carried out using different isolated preparations. The methanolic leaf extract potentiated both spontaneous and electrically evoked contractions of vas deferens of rats and guinea-pig ileum in a concentration dependent manner. The effect was not antagonized by the adrenergic blocker, tolazoline. The extract inhibited electrically stimulated neurogenic twitch responses of rat phrenic nerve diaphragm preparation. The dose dependent inhibition of twitch response in this preparation could not be reversed by the anticholinesterase drug, neostigmine. The extract evoked a persistent depolarizing effect on the phrenic nerve diaphragm preparation. The extract exhibited its most potent action on the isolated right atrial preparation of rat. It inhibited the rate of spontaneously beating atria in a concentration dependent manner. The negative chronotropic effect was not antagonized either by antimuscarinic drug or adrenergic agonist.     

Inhibitory effects of Santolina chamaecyparissus extracts against spasmogen agonists

Several extracts of Santolina chamaecyparissus ssp. squarrosa antagonized in a concentration-dependent way the contractions of rat duodenum, guinea-pig ileum, rat vas deferens and rat uterus as induced by acetylcholine, histamine, noradrenaline, oxytocin and serotonin. Polar extracts were less active than apolar extracts, and it was necessary to assay the former at higher concentrations. Only the lyophilized aqueous extract produced a slight hypotensive effect when given intravenously at 150 mg/kg to urethananesthetized rats.     

Spasmolytic Activity of Cissampelous mucronata Leaf Extract

The aqueous leaf extract of Cissampelous mucronata (Menispermaceae) was studied for spasmolytic properties. The extract inhibited the responses of histamine, acetylcholine and nicotine on the guinea-pig ileum in a dose-related manner. The extract completely abolished the spontaneous pendular movement of the rabbit jejunum reversibly, and decreased gastrointestinal motility in mice. It did not modify the effect of Ca²⁺ on the guinea-pig ileum. Acute toxicity tests in mice established the i.p. LD₅₀ value of the extract to be 1698.24±77 mg/kg.