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.     

Antiinflammatory activity and effects on isolated smooth muscle of extracts from different Teucrium species

The present study analyses the antiinflammatory effects and the action on in vitro motility of methanol and dichloromethanol extracts and stems of four Teucrium species (T. flavum, T. cartaginenses, T. buxifolium and T. pumillum). The antiinflammatory activity was tested in the carrageenan-induced paw oedema in rats. T. flavum methanol (200 mg/kg, i.p.) and dichloromethanol (138 mg/kg, i.p.) extracts showed a significant anti-inflammatory effect through the 24 h experimental period and reduced the E_max induced by histamine and serotonin in vitro on guinea-pig ileum and rat uterus respectively. These extracts did not modify the contractile effects induced by acetylcholine on rat duodenum and noradrenaline on rat vas deferens. The methanol extracts of T. pumillum (50 mg/kg, i.p.) and T. buxifolium (26 mg/kg, i.p.) exhibited significant antiinflammatory effects only in the acute phase of the oedema (2 h) without affecting the chronic phase (24 h). In guinea-pig ileum, rat uterus and rat vas deferens, the methanol extract of T. pumillum reduced the maximal effect induced by histamine, serotonin and noradrenaline, respectively, whereas the methanol extract of T. buxifolium lacked any effect on the contractile activity induced by various agonists in vitro. When tested for antiinflammatory activity the methanol (200 mg/kg, i.p.) and dichloromethanol (200 mg/kg, i.p.) extracts of T. cartaginenses did not modify the oedematous response induced by carrageenan administration.     

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.     

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.     

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.     

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.     

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 Synclisia scabrida alkaloid B on some isolated muscle preparations

Alkaloid B reversibly blocked the responses of rat diaphragm to electrically induced stimulations via the phrenic nerve. The alkaloid had no effect on the responses of the diaphragm elicited by direct electrical stimulation. The responses of frog rectus abdominis muscle to acetylcholine were inhibited by alkaloid B.Alkaloid B reversibly antagonised the responses of rabbit duodenum to exogenously applied acetylcholine. The contractile effect of oxytocin on rat uterus was specifically inhibited by alkaloid B. The effects of alkaloid B on isolated muscle preparations were concentration-dependent. However, the effect of dopamine and noradrenaline on rat vas deferens was not altered by alkaloid B.     

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.     

Bisnordihydrotoxiferine and vellosimine from Strychnos divaricans root: Spasmolytic properties of bisnordihydrotoxiferine

Bisnordihydrotoxiferine and vellosimine, two tertiary indole alkaloids have been isolated from the root of Strychnos divaricans. Bisnordihydrotoxiferine antagonized in a nonspecific manner, oxytocin and acetylcholine induced contractions in the rat uterus and acetylcholine and histamine responses in the guinea-pig ileum. Bisnordihydrotoxiferine, like verapamil, produced effects on voltage dependent Ca²⁺ channels. For example in guinea-pig ileum, bisnordihydrotoxiferine (pD'₂ 3.92±0.09) and verapamil (pD'₂ 6.00±0.11) inhibited KCl induced contractions. Furthermore, bisnordihydrotoxiferine (pD'₂ 4.37±0.02) and verapamil (pD'₂ 6.83±0.10) also antagonized CaCl₂ induced contractions of K⁺-depolarized rat uterus. When compared with sodium nitroprusside, an antagonist of receptor operated Ca²⁺ channels, bisnordihydrotoxiferine had no effect. However, in the aorta, the alkaloid (IC₅₀, 6.10 × 10^?6M) antagonized the intracellular calcium dependent transient contractions of noradrenaline and it was about four times more potent than procaine (IC₅₀, 2.30 × 10^?5M), a known inhibitor of the release of Ca²⁺ from intracellular stores. Bisnordihydrotoxiferine may produce nonspecific spasmolytic actions mainly by inhibiting intracellular calcium mobilization and to a lesser extent by inhibiting voltage dependent calcium channels in smooth muscles.     

The pharmacological basis for the use of dried sheep placenta in traditional obstetric practice in Nigeria

Dried sheep placenta is sometimes used in traditional medicine to facilitate labour. The effects of an extract of powdered dried sheep placenta with normal saline on guinea-pig uterus, ileum, spontaneously beating atrium and Langendorff heart, rat uterus and hindquarters, and cat blood pressure were therefore examined. It was found that 1 g of dried sheep placenta had, on the guinea-pig uterus, an oxytocic activity equipotent with 0.075-0.32 i.u. of oxytocin. The oxytocic activity was unaffected at pHs between 4 and 10 or by boiling for 30 min or autoclaving for 15 min. Neither atropine nor promethazine inhibited the oxytocic action, but promethazine inhibited, to the same degree, contractions induced in the ileum by equipotent doses of the infusion and histamine. Atropine, however, had no effect on infusion-induced contractions in the ileum. The vasoconstriction induced in the rat hindquarters was antagonized by promethazine and phentolamine. Cat blood pressure was reduced, but it had positive inotropic and chronotropic effects on the spontaneously beating guinea-pig atrium and on the guinea-pig Langendorff heart. It was concluded that the dried placenta contains a chorionic oxytocic substance the action of which is independent of stimulation of H₁ receptors or of muscarinic receptors.     

Differential antagonistic effect of hydroalcoholic extract from Hymenaea martiana hayne arzeik on kinin and other agonist-induced contractions of the isolated rat uterus and Guinea-pig ileum

This study was undertaken to evaluate the action of the hydroalcoholic extract (HE) from the bark of Hymenaea martiana on bradykinin (BK), lysyl-bradykinin (L-BK), acetylcholine (ACh), angiotensin II (AII), prostaglandin F_2a (PGF_2a), serotonin (5-HT), oxytocin (Ot) and histamine (His)-induced contractions of the isolated rat uterine muscle and guinea-pig ileum. The HE (50–200 μg/mL) added to the bath for 20 min caused a concentration-dependent rightward displacement of BK, L-BK and ACh-induced contractions in the rat uterus, allied to a discrete but significant reduction of maximal responses to the latter two agonists. By contrast, at the same range of concentrations the HE antagonized in a concentration-dependent but noncompetitive manner the contractions induced by AII, but only at high concentrations (200 μg/mL) it significantly inhibited contractions evoked by both PGF_2a and Ot, while contractile responses induced by 5-HT were not affected. In the guinea-pig ileum, the HE of H. martiana (50 and 100 μg/ml) caused a discrete rightward displacement of the BK and ACh concentration—response curves. Higher concentrations of the HE of H. martiana (200 μg/mL) caused a marked depression of BK and ACh-induced maximal responses. These findings show that the active principle(s) presents in the HE from the bark of H. martiana exhibits an interesting pharmacological profile against several neurotransmitter-induced contractions in nonvascular smooth muscles. Such actions may be relevant for supporting, at least in part, the use of this plant in folk medicine.     

Pharmacological Actions of Naringin on Alpha,Beta-adrenoceptors and Uptake of Noradrenaline in Rat Isolated Vas Deferens

In normal Krebs solution, naringin (1×10⁻⁷ M sc–2×10⁻⁶ M ) enhanced noradrenaline-induced contractions in rat isolated vas deferens increasing this potentiation in a concentration dependent manner. This enhancing effect continued in the presence of yohimbine (10⁻⁶ M ) or propranolol (10⁻⁶ M ). Naringin did not modify significantly the dopamine dose-response curves. In a medium containing 10⁻⁸ M prazosin, naringin decreased noradrenaline dose-response curves underneath the control curve at all the doses tested. Naringin did not modify significantly the NA dose-response curve in a medium containing cocaine (10⁻⁵ M ) or oestradiol (10⁻⁵ M ). The potentiation produced by naringin on the NA-induced contractions in rat vas deferens may be due to alpha-1 receptor activation, together with an interference of naringin in catecholamine uptake process.     

Globularia alypum L. extracts reduced histamine and serotonin contraction in vitro

The present study analyses in in vitro models the pharmacological activity of methanol and dichloromethane extracts (1, 10 and 100 microg/mL) obtained from the leaves and stems of Globularia alypum L. Preincubation of the guinea-pig ileum and rat uterus with both extracts produced a dose dependent abolition of the contractile effects of histamine and serotonin, respectively. At the same doses, neither methanol nor dichloromethane extract reduced the contractile effects of acetylcholine on rat duodenum or noradrenaline on rat vas deferens.     

连翘对豚鼠离体回肠运动的影响

目的:观察连翘对豚鼠离体肠管运动的影响,以期探讨其止呕作用的机制。方法:以呕吐相关受体激动剂为工具药,利用离体恒温浴槽,观察连翘对豚鼠离体回肠收缩的影响。结果:连翘能够抑制离体肠管的自发活动,表现为收缩张力降低,并呈剂量依赖性关系。乙酰胆碱(acetylcholine,Ach)、组织胺(histamine,His)、五羟色胺(5-hydroxytryptamine,5-HT)能够兴奋肠管,使张力升高、振幅变大,连翘高(10 g·L-1)、中(5 g·L-1)、低(2 g·L-1)剂量均能抑制以上3种工具药所致肠管收缩,降低其收缩张力和振幅,但对频率无明显影响。多巴胺(dopamine,DA)能够抑制肠管收缩,表现为张力降低、振幅变小,连翘高剂量和中剂量能够拮抗DA的肠管松弛作用,使张力升高、振幅变大;连翘低剂量能够进一步使张力降低,但使振幅增大。结论:连翘可以抑制豚鼠回肠运动,其机制可能是通过阻断肠平滑肌上的M受体、H1受体、5-HT受体和D2受体,也可能是对肠管的直接抑制作用,其止呕机制尚待进一步深入研究。     

Antispasmodic property of the aqueous extract of Aristolochia albida Duch

The antispasmodic property of the underground parts of Aristolochia albida Duch (family: Aristolochiaceae) was evaluated. The evidence was provided by the aqueous extract of the plant's rhizome which exhibited significant relaxation of the spontaneous pendular contraction of isolated rabbit duodenum. The extract at moderate doses abolished acetylcholine (Ach), histamine and 5-hydroxytryptamine (5-HT) induced contractions on isolated rabbit duodenum and guinea-pig ileum. The effects of the extract mimicked antagonists (atropine, mepyramine and methysergide). Therefore, the extract evoked its antispasmodic actions by antagonism via muscarinic, histaminic and 5-HT receptors. © 1997 John Wiley & Sons, Ltd.     

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 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.     

Further studies on the antidiarrhoeal activity of bisnordihydrotoxiferine,a tertiary indole alkaloid in rodents

The dimeric tertiary indole alkaloid bisnordihydrotoxiferine isolated from the root bark of Strychnos trinervis (Vell.) Mart. inhibited, on i.p. administration, Escherichia coli-induced diarrhoea and cholera toxin-stimulated intestinal fluid accumulation in mice. The respective ED₅₀ values were 10.6 and 20.0 mg/kg. The activity of bisnordihydrotoxiferine was unaffected by nalorphine or yohimbine, suggesting that the opioid and α₂-adrenoceptors respectively, are not important for its antidiarrhoeal action. In smooth muscle studies, bisnordihydrotoxiferine antagonized in a noncompetitive and reversible manner, the contractions produced by histamine, acetylcholine and substance P in guinea-pig ileum and by 5-hydroxytryptamine and arachidonic acid in rat fundic strip. The respective pD'₂ values (mean ± SEM) were 5.21 ± 0.29, 5.20 ± 0.29, 5.35 ± 0.12, in the ileum and 4.95 ± 0.13 and 3.66 ± 0.12 in the fundic strip. The values of slopes of the regression lines differed significantly from unity in all cases. Bisnor was inactive against PGE₂-induced contractions in the ileum. The mechanism of action of the alkaloid may be related to nonspecific antagonism of gastrointestinal smooth muscle stimulant activity of several endogenous substances.     

In vitro pharmacological evaluation of the dichloromethanol extract from Schinus molle l.

The pharmacological activity of the dichloromethanol extract of Schinus molle L. (SM-DCM) was analysed in in vitro models. Preincubation of the isolated guinea-pig ileum or rat uterus preparations with the extract (100 μg/mL) abolished the contractile effects of histamine and serotonin respectively. At the same dose, the extract partially reduced the contractile effects of acetylcholine on the isolated rat duodenum. A 10 μg/mL dose showed an inhibitory effect on histamine and serotonin, but not on acetylcholine-induced contractions (NS). No significant effect was found with a 1 μg/mL dose. © 1998 John Wiley & Sons, Ltd.