The nature of the sheep chorionic oxytocic substance

The effects of infusions of fresh sheep placenta in normal saline and the filtrate obtained therefrom after boiling for 15 min were investigated on guinea-pig and rat uteri, other mammalian non-vascular smooth muscles and the cardiovascular system, noting their responses to the infusion/filtrate in the presence or absence of various inhibitors or agonists. Solvent partition, acute toxicity and thin layer chromatography (TLC) studies were also performed. It was found that the infusion/filtrate had oxytocic activity independent of histamine and muscarinic receptors. It had H(1) receptor activity agonist action on the guinea-pig ileum, antagonized adrenaline-induced contractions in the vas but unlike bradykinin did not relax rat duodenum. It induced vasoconstriction in the rat hindquarters, depressed cat blood pressure but had positive inotropic effect on the guinea-pig Langendorff heart. Only the eluent from the least mobile of the five TLC bands on silica gel had oxytocic activity. It was concluded that the sheep chorionic oxytocic substance is not acetylcholine, histamine, 5-hydroxytryptamine, noradrenaline, adrenaline, prostaglandins F or E but is a peptide, which is not bradykinin, vasopressin or oxytocin.     

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.     

Effects of ethanol extract of Moringa stenopetala leaves on guinea-pig and mouse smooth muscle.

The fresh leaf ethanol (LE) extract of Moringa stenopetala was tested in guinea-pig ileum and mouse duodenum and in uterus strips. There were significant dose and time dependent reductions of the acetylcholine (AC) response with initial stimulatory effects in both the guinea-pig ileum and the mouse duodenum preparations. Spontaneous rhythmic contractions were greatly reduced, suggesting an antispasmodic property of the crude LE extract. The LE extract showed some oxytocic activity on uterus strips of guinea-pigs and mice. The results are indicative of the traditional use of the leaves of Moringa stenopetala for stomach pain and to expel retained placentae by women.     

Hypotensive and spasmolytic activities of ethanolic extract of Capparis cartilaginea

An ethanolic extract of Capparis cartilaginea (CC) at a dose of 1–10 mg/kg caused a dose-dependent fall in blood pressure and heart rate in anaesthetized rats. These effects were not blocked by atropine (1 mg/kg) and pretreatment with CC did not alter the pressor response to norepinephrine, indicating that the cardiovascular effects of CC are independent of cholinergic or adrenergic receptor involvement. In spontaneously beating guinea-pig atria, CC induced a concentration-dependent (0.1–1 mg/mL) decrease in force and rate of atrial contractions. In rabbit thoracic aorta, CC caused inhibition of norepinephrine or K⁺-induced contractions. In guinea-pig ileum, CC (1 mg/mL) inhibited submaximal contractions induced by acetylcholine, histamine or 5-HT. Spontaneous contractions of rat uterus were also abolished when CC was added to the tissue bath at similar concentrations. These results suggest that the direct relaxant action of CC on myocardium and blood vessels may be responsible for its hypotensive and bradycardiac effects observed in the in vivo studies. Moreover, CC exhibits general spasmolytic activity in different smooth muscle preparations.     

Pharmacological analysis of the inhibitory effect of jatrophone,a diterpene isolated from Jatropha elliptica,on smooth and cardiac muscles

The present work was conducted to analyse the effect of the diterpene jatrophone on drug and electrically evoked contractions of cardiac and smooth muscle preparations. Pre-incubation of the isolated rat uterus with jatrophone (1–100 μM ), for 20 min caused a decrease in the maximal contractions and a rightward displacement of the dose-response curves to acetylcholine, bradykinin, and oxytocin. In the isolated longitudinal muscle from guinea-pig ileum, jatrophone (1.6–12.8 μM ) produced a concentration-dependent inhibitory effect of acetylcholine, bradykinin and histamine-induced contractions. In this tissue, jatrophone was about 5 to 8-fold more potent in inhibiting acetylcholine and bradykinin than in uterine muscle. In strips of guinea-pig ileum, guinea-pig urinary bladder, rat left atrium electrically stimulated, and dog ureter contractions, jatrophone (1–100 μM ) caused a concentration-dependent inhibitory effect. In preparations electrically stimulated, jatrophone was about 2.5 to 23-fold less potent compared to those values obtained against agonist-induced contractions in the guinea-pig ileum. These results demonstrate that jatrophone exerts direct inhibitory effect on cardiac and smooth muscle preparations and show that its inhibitory potency may vary according to the tissue and/or stimulus employed to induce muscle contractions.     

Effects of the flavone luteolin,isolated from Colchicum richii,on guinea-pig isolated smooth muscle and heart and on blood pressure and blood flow

The effects of the flavone luteolin, extracted from Colchicum richii, on guinea-pig isolated ileum, pulmonary artery, trachea, atrium, perfused heart, and on blood pressure and blood flow of anaesthetized guinea-pigs were studied. Luteolin (10^?5?3 × 10^?4 M) caused concentration-dependent relaxation of the tone of ileum, epinephrine-precontracted pulmonary artery and only mild relaxation of acetylcholine-precontracted trachea. These effects were not affected by pretreatment with 1 mM theophylline except in the ileum where theophylline shifted to the left the luteolin concentration-effect curve. Luteolin (3 × 10^?6?3 × 10^?4 M) caused an increase in the beating rate and the contractility of the spontaneously beating atrium and of the isolated perfused heart. Theophylline (1 mM) significantly inhibited the effects of luteolin on the atrium and the perfused heart. Luteolin, in doses of 0.3, 1.0, 1.5 and 5 mg/kg body weight had no effect on heart rate of anaesthetized guinea-pigs but caused depression of systolic and diastolic blood pressure except at the lowest dose used where there was a small increase in both parameters. Also, only the lowest dose (0.3 mg/kg) caused a small increase in blood flow. Larger doses of luteolin caused dose-related inhibition of blood flow. The effects of luteolin on blood pressure and blood flow were not affected by theophylline pretreatment (5 mg/kg). These observations suggest that the effects of luteolin may be tissue-specific and in the isolated heart they may be attributed to inhibition of cyclic AMP phosphodiesterase. The data further demonstrate that luteolin has potential cardiovascular effects that merit further investigation.     

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.     

Pharmacological effects of Agapanthus africanus on the isolated rat uterus.

The Agapanthus africanus plant is used by South African traditional healers as a phytomedicine in herbal remedies to treat pregnancy-related ailments and to augment labour. It has already been shown that an aqueous extract of A. africanus causes smooth muscle contractions in the isolated uterus and ileum preparations. In the present study, the effects of an aqueous extract of A. africanus leaves was examined on receptor systems involved in contraction of the uterine smooth muscle in order to determine the mechanism of its pharmacological effect relevant to its ethnic use to augment labour. The extract was tested on the isolated rat uterus preparation. The aqueous extract of A. africanus leaves was found to exhibit agonist activity on uterine muscarinic receptors and to promote the synthesis of prostaglandins in the oestrogenized rat uterus. Some pharmacological justification for the ethnic use of A. africanus as a herbal oxytocic in prolonged labour has been provided.     

Effect of ambrein on smooth muscle responses to various agonists

The pharmacological effects of ambrein (isolated from ambergris) on the contractile responses induced by some agonists in smooth muscle preparations were investigated. Ambrein in the concentration range of 10, 50 and 250 μg/ml decreased the spontaneous contraction of the isolated rabbit jejunum, rat uterus and guinea-pig vas deferens. Ambrein-induced antagonism to acetylcholine (Ach) in the guinea-pig ileum was abolished when the concentration of calcium chloride in the Tyrode's solution was increased to 5 mM/l. Furthermore, ambrein did not antagonise nicotine-induced contractions in the isolated rabbit jejunum or serotonin-induced contractions in the isolated guinea-pig ileum and vas deferens or the rat uterus. However, ambrein in the concentration range of 10, 50 and 250 μg/ml antagonised prostaglandins (PGs) E₂, D₂, F_2α, and oxytocin-induced contractions in the rat uterus in vitro. Ambrein also antagonised (±) noradrenaline and (−) adrenaline-induced contractions in the isolated guinea-pig vas deferens. It is concluded that ambrein-induced non-selective dose-dependent antagonism to the effects of some agonists (Ach, adrenaline, noradrenaline, PGs and oxytocin) in some smooth muscles may be due to the ability of this compound to interfere with the mobilisation of extracellular Ca²⁺ required for muscular contractions induced by these agonists.     

Inhibition of gastrointestinal release of acetylcholine by quercetin as a possible mode of action of Psidium guajava leaf extracts in the treatment of acute diarrhoeal disease

The electrically stimulated guinea-pig ileum and spontaneously contracting guinea-pig ileum preparations were employed in studies on the effects of an alcoholic extract and two flavonoid compounds, quercetin and quercetin-3-arabinoside, extracted from the leaves of Psidium guajava. The extract showed a morphine-like inhibition of acetylcholine release in the coaxially stimulated ileum, together with an initial increase in muscular tone, followed by a gradual decrease. The morphine-like inhibition was found to be due to quercetin, starting at concentrations of 1.6 micrograms/ml. The glycoside did not show any such action at concentrations of up to 1.28 mg/ml. The extract inhibited spontaneous contractions in the unstimulated ileum with a concentration-response relationship.     

Preliminary isolated organ studies using an aqueous extract of Clivia miniata leaves

An infusion of Clivia miniata leaves is a traditional medicine taken by Black South African women to induce or augment labour. A boiling water extract of C. miniata leaves was studied for its pharmacological effects on rat uterus and ileum. The extract caused concentration-dependent contractions in both the uterus and ileum, but at a fraction of the intrinsic activity of acetylcholine. When the organs were pretreated with the extract before the cumulative addition of either oxytocin or acetylcholine, the extract augmented the initial response of the organs to the reference drugs. The frequency of contractions in the spontaneously contracting uterus was increased by the presence of the extract. C. miniata extract, however, inhibited the maximal response of the ileum to acetylcholine in a non-competitive way. It did not affect the maximal response of the uterus to either oxytocin or acetylcholine.     

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.     

A drug used in traditional medicine: Harpagophytum procumbens DC II. Cardiovascular activity

In conscious normotensive rats the dried crude methanolic extract of Harpagophytum procumbens secondary roots caused a significant dosedependent reduction of arterial blood pressure. The decrease was significant only at higher doses given by gavage (dried extract = 400 $\text{mg}\text{kg}$). At the same time a decrease of heart rate was observed.In the same experimental conditions, harpagoside presented an activity lower than doses of Harpagophytum procumbens extract containing corresponding quantities of harpagoside.In spontaneously beating Langendorff preparations of rabbit heart, the Harpagophytum procumbens methanolic extract caused a mild decrease in the heart rate with a concomitant mild positive inotropic effect at lower doses but a marked negative inotropic effect at higher doses. The coronary flow decreased at higher doses only.The negative chronotropic and positive inotropic effects of harpagoside were comparatively higher with respect to that of the extract, whereas harpagide had only a slight negative chronotropic effect and a considerable negative inotropic one.Both in experiments on intact rats and on isolated rabbit heart, the Harpagophytum procumbens extract also demonstrated a protective action with regard to arrhythmias induced by aconitine, and particularly to those provoked by calcium chloride and epinephrine—chloroform.     

The pharmacological effects of an aqueous extract from Acacia nilotica seeds

An aqueous extract of the seed of Acacia nilotica was investigated for its pharmacological profile. On the isolated guinea-pig ileum, the extract displayed sustained dose-related contractile activity. The contractions which were reduced by hexamethonium, promethazine or atropine were completely abolished by nifedipine. The intravenous (i.v.) administration of the extract (11, 22, 44, 55 microg/kg) to anaesthetized cats produced a dose-related significant elevation of blood pressure. The mechanisms of the spasmogenic and vasoconstrictor actions of the extract have not been determined, however, the results suggest the involvement of calcium.     

The source of ca2+ for the spasmolytic actions of longicaudatine,a bisindole alkaloid isolated from Strychnos trinervis (Vell.) Mart. (Loganiaceae)

Longicaudatine, a tertiary bisindole alkaloid isolated from the root bark of Strychnos trinervis (Vell.) Mart. (Loganiaceae), antagonized in a noncompetitive manner, carbachol and histamine induced contractions of the guinea-pig ileum and bradykinin responses in the rat uterus. The respective pD₂' values (mean ± SE) were 4.61 ± 0.21, 4.98 ± 0.04 and 4.49 ± 0.01. Longicaudatine, unlike verapamil, had no effect on voltage dependent Ca²⁺ channels, as it failed to inhibit KCI or CaCl₂ induced contractions of guinea-pig ileum and depolarized rat uterus respectively. When compared with sodium nitroprusside, an antagonist of receptor operated Ca²⁺ channels, longicaudatine produced a slower and weaker inhibition of noradrenaline induced sustained contractions of rabbit aortic strips. However, in the aorta, the alkaloid antagonized the intracellular calcium dependent transient contractions of noradrenaline and longicaudatine (IC₅₀, 5.01 × 10^?7 M) was approximately 133 times more potent that procaine (IC₅₀, 6.68 × 10^?5 M), a known inhibitor of the release of Ca²⁺ from intracellular stores. Longicaudatine may exert nonspecific spasmolytic effects by acting on intracellular Ca²⁺ stores, rather than on depolarization dependent or receptor operated Ca²⁺ channels.     

Contractile response induced by a limonoid (humilinolide A) on spontaneous activity of isolated smooth muscle

The in vitro effect of the limonoid humilinolide A, isolated from Swietenia humilis (Meliaceae), on spontaneous contractions of guinea-pig ileum, and uterus from oestrus, dioestrus, ovariectomized and oestrogen-primed rats was studied. Humilinolide A caused a concentration dependent and non-reversible excitatory effect on intestinal and uterine smooth muscle, distinguished as spasmogenic and uterotonic action respectively. However, the potency of this compound to induce contraction was different in the distinct preparations assayed: in ileal musculature of male guinea-pigs, as well as in uterine muscle of dioestrus and ovariectomized rats, a slight excitatory effect was observed; in contrast to an intense excitatory effect displayed in rat uterus with high oestrogen levels (oestrus and oestrogenized). These data suggest that the contractile response induced by humilinolide A could be mediated by oestrogens, probably by occupancy of some receptors in myometrial plasma membranes to induce uterotonic response, which may be oestrogen-dependent. © 1997 John Wiley & Sons, Ltd.     

The pharmacological action of Rhoicissus tridentata on isolated rat uterus and ileum

Decoctions and infusions of Rhoicissus tridentata subsp cuneifolia (Vitaceae) roots and lignotubers are widely used in South African traditional herbal remedies during pregnancy. The pharmacological action of an aqueous extract of R. tridentata subsp cuneifolia roots was investigated using isolated rat uterus and ileum. The extract directly stimulated concentration dependent contractions of the uterus and ileum. Pretreatment with the muscarinic antagonist atropine (40 nM) and the cyclooxygenase inhibitor indomethacin (5 microM) both blocked the contractile response to the Rhoicissus extract suggesting that muscarinic receptors and cyclooxygenase metabolites could be involved in the contractile response to the extract. The serotonergic antagonist methysergide (1 microM) and the alpha-adrenoceptor antagonist prazosin (2 microM) had no effect on the direct action of the extract. This infers that the contractile response to the plant extract is independent of serotonin receptors and alpha-adrenoceptors.     

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 actions of warifteine,a bisbenzylisoquinoline alkaloid isolated from the root bark of Cissampelos sympodialis Eichl. (menispermaceae)

Warifteine, a bisbenzylisoquinoline alkaloid isolated from the root bark of Cissampelos sympodialis Eichl., produced a reversible, nonspecific and noncompetitive antagonism of histamine, carbachol and bradykinin induced contractions of the guinea-pig ileum. The corresponding pD'₂ values (mean±SE) were 4.90±0.15, 4.95±0.20 and 5.03±0.11. Warifteine also antagonized oxytocin and bradykinin induced contractions of the rat uterus in a similar manner with pD'₂ values of 4.30±0.26 and 3.76±0.06 respectively. In the guinea-pig trachea, the alkaloid inhibited spontaneous tone (IC₅₀, 1.1 × 10^?5M) as well as carbachol induced sustained contractions (IC₅₀, 2.9 × 10^?5M). As warifteine antagonized KCI induced contractions of the guinea-pig ileum (pD'₂ value 4.57±0.10), inhibition of Ca⁺⁺ influx through voltage operated Ca⁺⁺ channels may be partially responsible for its antispasmodic activity. However, the reported local anaesthetic property of warifteine may not contribute to the observed muscle relaxation as procaine failed to reduce the spontaneous tone or consistently antagonize carbachol induced contractions of the trachea and was inactive in inhibiting voltage operated Ca⁺⁺ channels in the ileum.     

Oxytocic and oestrogenic effects of Monechma ciliatum methanol extract in vivo and in vitro in rodents

Various solvent extracts of the leaves of Monechma ciliatum (family Acanthecaea) were tested for oxytocic properties on uterine preparations in vivo and in vitro. The methanol extract (HME) contracted the nonpregnant uterus of the rat, guinea-pig and mouse as well as preparations obtained from guinea-pigs on days 6–7 and 11–12 of pregnancy. The rat pregnant uterus was not affected by the extract. Oral administration of HME to rats on days 15, 16 and 17 of pregnancy had no abortifacient effect compared with oxytocin. However, laparotomy on day 23 revealed fetal death in utero. The extract was also found to have oestrogenic activity based on parameters such as uterine weight ratio, premature vaginal opening and degree of vaginal cornification.