Gut modulatory, blood pressure lowering, diuretic and sedative activities of cardamom

ETHNOPHARMACOLOGICAL RELEVANCE: Cardamom (Elettaria cardamomum) is traditionally used in various gastrointestinal, cardiovascular and neuronal disorders. AIM OF THE STUDY: To rationalize cardamom use in constipation, colic, diarrhea, hypertension and as diuretic. MATERIALS AND METHODS: Cardamom crude extract (Ec.Cr) was studied using in vitro and in vivo techniques. RESULTS: Ec.Cr caused atropine-sensitive stimulatory effect in isolated guinea-pig ileum at 3-10mg/ml. In rabbit jejunum preparations, Ec.Cr relaxed spontaneous and K+ (80 mM)-induced contractions as well as shifted Ca++ curves to right, like verapamil. Ec.Cr (3-100mg/kg) induced fall in the arterial blood pressure (BP) of anaesthetized rats, partially blocked in atropinized animals. In endothelium-intact rat aorta, Ec.Cr relaxed phenylephrine (1 microM)-induced contractions, partially antagonized by atropine and also inhibited K+ (80 mM) contractions. In guinea-pig atria, Ec.Cr exhibited a cardio-depressant effect. Ec.Cr (1-10mg/kg) produced diuresis in rats, accompanied by a saluretic effect. It enhanced pentobarbital-induced sleeping time in mice. Bio-assay directed fractionation revealed the separation of spasmogenic and spasmolytic components in the aqueous and organic fractions respectively. CONCLUSION: These results indicate that cardamom exhibits gut excitatory and inhibitory effects mediated through cholinergic and Ca++ antagonist mechanisms respectively and lowers BP via combination of both pathways. The diuretic and sedative effects may offer added value in its use in hypertension and epilepsy.     

Mechanisms underlying the antispasmodic and bronchodilatory properties of Terminalia bellerica fruit

AIM OF THE STUDY: The present investigation was carried out to provide the pharmacological basis for the medicinal use of Terminalia bellerica in hyperactive gastrointestinal and respiratory disorders. MATERIALS AND METHODS: Crude extract of Terminalia bellerica fruit (Tb.Cr) was studied in in vitro and in vivo. RESULTS: Tb.Cr caused relaxation of spontaneous contractions in isolated rabbit jejunum at 0.1-3.0mg/mL. Tb.Cr inhibited the carbachol (CCh, 1microM) and K(+) (80mM)-induced contractions in a pattern similar to that of dicyclomine, but different from nifedipine and atropine. Tb.Cr shifted the Ca(++) concentration-response curves to right, like nifedipine and dicyclomine. In guinea-pig ileum, Tb.Cr produced rightward parallel shift of acetylcholine-curves, followed by non-parallel shift at higher concentration with the suppression of maximum response, similar to dicyclomine, but different from nifedipine and atropine. Tb.Cr exhibited protective effect against castor oil-induced diarrhea and carbachol-mediated bronchoconstriction in rodents. In guinea-pig trachea, Tb.Cr relaxed the CCh-induced contractions, shifted CCh-curves to right and inhibited the contractions of K(+). Anticholinergic effect was distributed both in organic and aqueous fractions, while CCB was present in the aqueous fraction. CONCLUSIONS: These results indicate that Terminalia bellerica fruit possess a combination of anticholinergic and Ca(++) antagonist effects, which explain its folkloric use in the colic, diarrhea and asthma.     

Coriander fruit exhibits gut modulatory,blood pressure lowering and diuretic activities

Aim of the study

Coriander (Coriandrum sativum) is traditionally used for various gastrointestinal and cardiovascular disorders and this study was designed to rationalize its use in dyspepsia, abdominal colic, diarrhea, hypertension and as diuretic.

Materials and methods

Coriander crude extract (Cs.Cr) was evaluated through in vitro and in vivo techniques.

Results

Cs.Cr caused atropine sensitive stimulatory effect in isolated guinea-pig ileum (0.1–10 mg/ml). In rabbit jejunum preparations, Cs.Cr evoked a similar contractile response but in the presence of atropine, it exhibited relaxation against both spontaneous and high K⁺ (80 mM)-induced contractions as well as shifted the Ca²⁺ concentration–response curves to right, similar to that caused by verapamil. Cs.Cr (1–30 mg/ml) caused fall in arterial blood pressure of anesthetized animals, partially blocked by atropine. Cs.Cr produced vasodilatation against phenylephrine and K⁺ (80 mM)-induced contractions in rabbit aorta and cardio-depressant effect in guinea-pig atria. Cs.Cr produced diuresis in rats at 1–10 mg/kg. Bio-assay-directed fractionation revealed the separation of spasmogenic and spasmolytic components in the aqueous and organic fractions respectively.

Conclusions

These results indicate that coriander fruit exhibits gut stimulatory, inhibitory and hypotensive effects mediating possibly through cholinergic, Ca²⁺ antagonist and the combination of these mechanisms respectively. Diuretic activity adds value to its use in hypertension.     

Studies on spasmogenic and spasmolytic activities of Calendula officinalis flowers

The aqueous-ethanol extract of Calendula officinalis flowers (Co.Cr) was studied for its possible spasmolytic and spasmogenic effects in isolated gut preparations. In rabbit jejunum, Co.Cr caused a dose-dependent (0.03-3.0 mg/mL) relaxation of spontaneous and K+-induced contractions, suggestive of calcium channel blockade (CCB). In a few preparations, a mild non-reproducible spasmogenic effect was observed at lower doses, followed by relaxation. The CCB effect was confirmed when pretreatment of the jejunum preparations with Co.Cr produced a dose-dependent rightward shift in the Ca(++) dose-response curves, similar to that of verapamil. Activity-directed fractionation revealed that the spasmolytic activity of the plant was concentrated in its organic fractions. The aqueous fraction exhibited a marked atropine sensitive spasmogenic effect but was found to be devoid of any spasmolytic effect. These data indicate that the crude extract of Calendula officinalis flowers contains both spasmolytic and spasmogenic constituents, exhibiting these effects through calcium channel blocking and cholinergic activities and this study provides a scientific base for its traditional use in abdominal cramps and constipation.     

Ethnopharmacological studies on antispasmodic and antiplatelet activities of Ficus carica

ETHNOPHARMACOLOGICAL RELEVANCE: The ripe dried fruit of Ficus carica Linn. (Moraceae) commonly known as "Fig" has medicinal value in traditional system of medicine for its use in gastrointestinal and inflammatory disorders. AIM OF THE STUDY: To rationalize the medicinal use of Fig (Ficus carica) in gastrointestinal and inflammatory disorders. MATERIALS AND METHODS: The aqueous-ethanolic extract of Ficus carica (Fc.Cr) was studied for antispasmodic effect on the isolated rabbit jejunum preparations and for antiplatelet effect using ex vivo model of human platelets. RESULTS: Fc.Cr tested positive for alkaloids, flavonoids, coumarins, saponins, sterols and terpenes. When tested in isolated rabbit jejunum, Fc.Cr (0.1-3.0mg/mL) produced relaxation of spontaneous and low K(+) (25mM)-induced contractions with negligible effect on high K(+) (80mM) similar to that caused by cromakalim. Pretreatment of the tissue with glibenclamide caused rightward shift in the curves of low K(+)-induced contractions. Similarly, cromakalim inhibited the contractions induced by low K(+), but not of high K(+), while verapamil equally inhibited the contractions of K(+) at both concentrations. Fc.Cr (0.6 and 0.12mg/mL) inhibited the adenosine 5'-diphosphate and adrenaline-induced human platelet aggregation. CONCLUSION: This study showed the presence of spasmolytic activity in the ripe dried fruit of Ficus carica possibly mediated through the activation of K(+)(ATP) channels along with antiplatelet activity which provides sound pharmacological basis for its medicinal use in the gut motility and inflammatory disorders.     

Antispasmodic and bronchodilator activities of Artemisia vulgaris are mediated through dual blockade of muscarinic receptors and calcium influx

Aim of the study

The present study describes antispasmodic, antidiarrheal, bronchodilatory and tracheo-relaxant activities of Artemisia vulgaris to rationalize some of its traditional uses.

Materials and methods

Crude extract of Artemisia vulgaris (Av.Cr) was studied in the isolated tissue preparations of rabbit jejunum and guinea-pig trachea, as well as in the in vivo castor oil-induced diarrhea and bronchodilatory techniques.

Results

Av.Cr which tested positive for alkaloids, coumarins, flavonoids, saponins, sterols, tannins and terpenes caused concentration-dependent (0.03–10 mg/mL) relaxation of jejunum spontaneous contractions. Av.Cr inhibited the carbachol (CCh, 1 μM) and K⁺ (80 mM)-induced contractions in a pattern, similar to that of dicyclomine. Av.Cr shifted the Ca²⁺ concentration–response curves to right, like that caused by verapamil and dicyclomine. Av.Cr produced rightward parallel shift in CCh-curves, followed by non-parallel shift at higher concentration with the suppression of the maximum response, similar to that caused by dicyclomine. It exhibited protective effect against castor oil-induced diarrhea and CCh-mediated bronchoconstriction in rodents. In trachea, Av.Cr relaxed the CCh (1 μM) and K⁺ (80 mM)-induced contractions and shifted the CCh-curves to right.

Conclusion

These results indicate that Artemisia vulgaris exhibits combination of anticholinergic and Ca²⁺ antagonist mechanisms, which provides pharmacological basis for its folkloric use in the hyperactive gut and airways disorders, such as abdominal colic, diarrhea and asthma.     

Cholinomimetic and calcium channel blocking activities of Carthamus oxycantha

The crude extract of Carthamus oxycantha (Co.Cr) and its fractions were studied in vitro for their possible spasmogenic and spasmolytic activities. Co.Cr (0.03-10 mg/mL) caused an atropine sensitive spasmogenic effect in guinea-pig ileum. In spontaneously contracting rabbit jejunum preparations, Co.Cr caused a dose-dependent (0.03-3.0 mg/mL) spasmogenic effect, followed by relaxation at the next higher doses of 5.0-10.0 mg/mL. In the presence of atropine, the spasmogenic effect was blocked and the relaxant effect was observed at lower doses (0.1-5.0 mg/mL), shifting the inhibitory dose-response curves to the left. Co.Cr also inhibited K(+) (80 mm)-induced contractions in atropinized preparations at similar doses, suggesting calcium channel blockade (CCB) activity. The CCB effect was further confirmed when pretreatment of the tissue with Co.Cr produced a dose-dependent shift in the Ca(++) dose-response curves to the right, similar to that caused by verapamil. Activity-directed fractionation revealed that the spasmolytic effect was concentrated in organic fractions in the following order of potency: hexane > ethylacetate > chloroform, while the aqueous fraction exhibited spasmogenic and weak spasmolytic effects. These results indicate that Carthamus oxycantha contains a combination of spasmogenic (cholinergic) and spasmolytic (calcium antagonist) constituents.     

Studies on the antihypertensive, antispasmodic, bronchodilator and hepatoprotective activities of the Carum copticum seed extract

This study describes the antihypertensive, antispasmodic, bronchodilator and hepatoprotective activities of the aqueous-methanolic extract of Carum copticum Benth. seeds (CSE) to rationalize some of its traditional uses. CSE (3-100 mg/kg) caused a dose-dependent fall in arterial blood pressure in anaesthetized rats. In isolated rabbit aorta and jejunum preparations, CSE (0.1-3.0 mg/ml) caused an inhibitory effect on the K+-induced contractions. The calcium channel blocking (CCB) effect was confirmed when CSE shifted the Ca2+ dose-response curves (DRCs) to right similar to verapamil. In isolated guinea-pig tracheal preparations, it caused inhibition of carbachol and K+-induced bronchoconstriction at 0.1-1.0 mg/ml as well as shifted the dose-response curves (DRCs) of carbachol and histamine to the right with suppression of maximum response suggestive of non-specific bronchodilator effect mediated possibly through CCB. Pretreatment of rats with CSE (500 mg/kg orally for 2 days at 12 h intervals) prevented paracetamol (640 mg/kg) and CCl4 (150 ml/kg)-induced rise in serum alkaline phosphatase (ALP) and aminotransferases (AST and ALT). The same dose of CSE was able to prevent the CCl4-induced prolongation in pentobarbital-induced sleeping time in mice confirming its hepatoprotectivity. These results indicate the presence of calcium antagonist(s) in Carum copticum seeds and thus provides sound mechanistic basis for some of their folkloric uses.     

Antispasmodic,bronchodilator and blood pressure lowering properties of Hypericum oblongifolium – possible mechanism of action

The crude extract of Hypericum oblongifolium (Ho.Cr), which tested positive for flavonoids, saponins and tannins caused concentration‐dependent (0.1–1.0 mg/mL) relaxation of spontaneous and high K⁺ (80 mM)‐induced contractions in isolated rabbit jejunum preparations, suggesting a Ca⁺⁺ antagonistic effect, which was confirmed when pretreatment of the tissue with Ho.Cr produced a rightward shift in the Ca⁺⁺ concentration‐response curves, like that caused by verapamil. Ho.Cr relaxed carbachol (1 μM) and high K⁺‐induced contractions in guinea pig tracheal preparations. It caused a dose‐dependent (3–100 mg/kg) fall in arterial blood pressure of rats under anesthesia. In isolated guinea pig atria, Ho.Cr caused inhibition of both atrial force and rate of spontaneous contractions. When tested in rabbit aortic rings, Ho.Cr exhibited a vasodilator effect against phenylephrine (1 μM) and high K⁺‐induced contractions. These results indicate that Ho.Cr possesses gastrointestinal, respiratory and cardiovascular inhibitory effects, mediated via a Ca⁺⁺ antagonist mechanism. Copyright © 2009 John Wiley & Sons, Ltd.     

Pharmacological basis for the medicinal use of Zanthoxylum armatum in gut,airways and cardiovascular disorders

This study describes the gut, airways and cardiovascular modulatory activities of Zanthoxylum armatum DC. (Rutaceae) to rationalize some of its medicinal uses. The crude extract of Zanthoxylum armatum (Za.Cr) caused concentration‐dependent relaxation of spontaneous and high K⁺ (80 mM)‐induced contractions in isolated rabbit jejunum, being more effective against K⁺ and suggestive of Ca⁺⁺ antagonist effect, which was confirmed when pretreatment of the tissues with Za.Cr shifted Ca⁺⁺ concentration‐response curves to the right, like that caused by verapamil. Za.Cr inhibited the castor‐oil‐induced diarrhea in mice at 300–1000 mg/kg. In rabbit tracheal preparations, Za.Cr relaxed the carbachol (1 μM) and high K⁺‐induced contractions, in a pattern similar to that of verapamil. In isolated rabbit aortic rings, Za.Cr exhibited vasodilator effect against phenylephrine (1 μM) and K⁺‐induced contractions. When tested in guinea pig atria, Za.Cr caused inhibition of both atrial force and rate of spontaneous contractions, like that caused by verapamil. These results indicate that Zanthoxylum armatum exhibits spasmolytic effects, mediated possibly through Ca⁺⁺ antagonist mechanism, which provides pharmacological base for its medicinal use in the gastrointestinal, respiratory and cardiovascular disorders. Copyright © 2009 John Wiley & Sons, Ltd.     

Antispasmodic and blood pressure lowering effects of Valeriana wallichii are mediated through K+ channel activation

Crude extract of Valeriana wallichii rhizome (Vw.Cr) and its fractions were studied for possible antispasmodic and blood pressure lowering activities to rationalize some of the folkloric uses. In rabbit jejunum preparations, Vw.Cr (0.1–3.0 mg/mL) caused relaxation of spontaneous contractions. When tested against high K⁺ (80 mM)-induced contractions it produced weak inhibitory effect, while caused complete relaxation of the contractions induced by low K⁺ (20 mM). In the presence of glibenclamide (3 μM), the inhibitory effect of low K⁺ was shifted to the right, similar to that produced by cromakalim while, verapamil caused no differentiation in its inhibitory effect against low and high K⁺-induced contractions. In guinea pig ileum, the plant extract produced similar results as in rabbit jejunum. Intravenous administration of Vw.Cr, produced fall in arterial blood pressure in normotensive anaesthetized rats and this effect was partially blocked by glibenclamide. In rabbit aortic preparations, plant extract also caused a selective and glibenclamide-sensitive relaxation of low K⁺ (20 mM)-induced contractions. Activity-directed fractionation studies revealed that the observed activity was distributed both in the chloroform and aqueous fractions. These results indicate that the antispasmodic and hypotensive effects of Valeriana wallichii are mediated possibly through K_ATP channel activation, which justify its use in gastrointestinal and cardiovascular disorders.     

Pharmacological basis for the use of peach leaves in constipation

The aqueous crude extract (PPL.Cr) of peach leaves (Prunus persica) was studied for the possible presence of gut stimulatory constituent(s) to rationalize the folkloric use of the plant in constipation. PPL.Cr at the dose of 1-10 mg/ml caused a moderate degree of spasmogenic effect in isolated guinea-pig ileum. Pretreatment of the tissue with atropine (1 M) completely abolished the contractile effect of the plant extract similar to that of acetylcholine which is suggestive of a cholinergic mechanism. In isolated rabbit jejunum preparations, PPL.Cr produced a week spasmogenic effect followed by relaxation of the spontaneous contractions at higher doses. Bioassay-directed fractionation revealed that the spasmogenic activity was separated in the aqueous fraction, while the spasmolytic activity was concentrated in the ethyl acetate fraction. When tested against K(+)-induced contraction, both PPL.Cr and its ethyl acetate fraction (PPL.EtAc) caused a dose-dependent inhibition, suggesting calcium channel blockade (CCB). The presence of CCB in peach leaves was confirmed when pretreatment of the tissue with PPL.EtAc caused a dose-dependent rightward shift in the Ca(2+) dose-response curves, similar to that produced by verapamil. These data indicate that the plant contains spasmogenic (cholinomimetic) and spasmolytic (calcium antagonist) constituents, which are concentrated in the aqueous and ethyl acetate fractions, respectively. Furthermore, the laxative effect of the plant reported in the traditional system of medicine may be partially due to the cholinergic action, which was dominant over the spasmolytic component.     

Pharmacological basis for the medicinal use of Carissa carandas in constipation and diarrhea

Ethnopharmacological relevance

Carissa carandas Linn. commonly known as “Karaunda” (Apocynaceae) is a popular medicinal herb widely distributed in different parts of Pakistan. In addition to other medicinal uses, Carissa carandas is popular in indigenous system of medicine for its medicinal use in gut motility disorders like, constipation and diarrhea.

Objective

This study was planned to provide pharmacological basis to the medicinal use of Carissa carandas in constipation and diarrhea.

Materials and methods

The crude extract of the leaves of Carissa carandas (Cc.Cr) was prepared in methanol and its fractionation was carried out with ethylacetate, petroleum ether and n-butanol. In-vivo studies were conducted on mice, while isolated rabbit jejunum and guinea-pig ileum preparations were used for the in-vitro experiments. The spasmogenic and spasmolytic responses of gut tissues were recorded using isotonic transducers coupled with PowerLab data acquisition system.

Results

The HPLC fingerprints of Cc.Cr, its petroleum (Cc.Pef), ethylacetate (Cc.Eaf) and n-butanol (Cc.Baf) fractions showed the presence of oleanolic acid, ursolic acid, stigmasterol and β-sitosterol. Oral administration of Cc.Cr to mice increased fecal output at lower doses (30 and 50 mg/kg), while it showed protection against castor oil-induced diarrhea at higher doses (300 and 600 mg/kg). In isolated guinea-pig ileum and rabbit jejunum, Cc.Cr and Cc.Baf exhibited stimulatory effect at 0.003–3 mg/ml, which was partially sensitive to atropine or pyrillamine or partially/fully sensitive to atropine+pyrillamine, followed by relaxation at higher tested concentrations, being more potent in rabbit tissues. The ethylacetate fraction (0.1–5 mg/ml) exhibited fully atropine-sensitive contractions in both guinea-pig and rabbit tissues, being more potent in guinea-pig while more efficacious in rabbit tissues. However, the petroleum fraction (0.003–1.0 mg/ml) showed only spasmolytic activity in spontaneously contracting rabbit tissues, similar to nifedipine. In guinea-tissue, Cc.Pef did not cause any stimulant effect. When studied against high K⁺ (80 mM)-induced contraction, the crude extract and its fractions caused a dose-dependent inhibition, with the following order of potency: Cc.Pef>Cc.Eaf>Cc.Cr≥Cc.Baf, similar to nifedipine indicating Ca⁺⁺ channel antagonist like activity, which was further confirmed when the plant extract displaced Ca⁺⁺ curves to the right with suppression of maximum effect similar to that of nifedipine.

Conclusion

This study demonstrates that the crude extract of Carissa carandas possesses a gut-stimulatory effect mediated primarily through the activation of muscarinic and histaminergic receptors while its spasmolytic effect was mediated possibly through Ca⁺⁺ antagonist pathway. Thus, this study provides a clear evidence for the dual effectiveness of Carissa carandas in constipation and diarrhea, thus validating its medicinal use.     

The antidiarrheal and spasmolytic activities of Phyllanthus emblica are mediated through dual blockade of muscarinic receptors and Ca2+ channels

Aim of the study

This study was aimed at providing the possible mechanisms for the medicinal use of Phyllanthus emblica in diarrhea.

Materials and methods

The in vivo studies were conducted in mice, while isolated rabbit jejunum and guinea-pig ileum were used for the in vitro experiments.

Results

The crude extract of Phyllanthus emblica (Pe.Cr), which tested positive for alkaloids, tannins, terpenes, flavonoids, sterols and coumarins, caused inhibition of castor oil-induced diarrhea and intestinal fluid accumulation in mice at 500-700 mg/kg. In isolated rabbit jejunum, Pe.Cr relaxed carbachol (CCh) and K⁺ (80 mM)-induced contractions, in a pattern similar to that of dicyclomine. The preincubation of guinea pig-ileum with Pe.Cr (0.3 mg/mL), caused a rightward parallel shift in the concentration-response curves (CRCs) of acetylcholine without suppression of the maximum response. While at the next higher concentration (1 mg/mL), it produced a non-parallel rightward shift with suppression of the maximum response, similar to that of dicyclomine, suggesting anticholinergic and Ca²⁺ channel blocking (CCB)-like antispasmodic effect. The CCB-like activity was further confirmed when pretreatment of the tissue with Pe.Cr, shifted the CRCs of Ca²⁺ to the right with suppression of the maximum response, similar to nifedipine or dicyclomine. The activity-directed fractions of Pe.Cr showed a combination of Ca²⁺ antagonist and anticholinergic like components in all fractions but with varying potency.

Conclusion

These results indicate that the Phyllanthus emblica fruit extract possesses antidiarrheal and spasmolytic activities, mediated possibly through dual blockade of muscarinic receptors and Ca²⁺ channels, thus explaining its medicinal use in diarrhea.     

Studies on antihypertensive and antispasmodic activities of methanol extract of Acacia nilotica pods

A methanol extract of Acacia nilotica pods (AN) caused a dose-dependent (3-30 mg/kg) fall in arterial blood pressure. Treatment of animals with atropine abolished the vasodilator response of acetylcholine (ACh), whereas the antihypertensive effect of the plant extract remained unaltered. Phentolamine (an alpha-adrenergic blocker) abolished the vasoconstrictor effect of norepinephrine (NE), whereas pretreatment of the animal with AN, did not modify the NE response. These results indicate that the antihypertensive effect of plant extract is independent of muscarinic receptor stimulation or adrenoceptor blockade. In the in vitro studies, AN produced a dose-dependent (0.3-3.0 mg/mL) inhibitory effect on force and rate of spontaneous contractions in guinea-pig paired atria. Similarly, it inhibited the spontaneous contraction of rabbit jejunum in a concentration-dependent (0.1-3.0 mg/mL) manner. AN also inhibited K(+)-induced contractions in rabbit jejunum at a similar concentration range, which suggests that the antispasmodic action of AN is mediated through calcium channel blockade, and this may also be responsible for the blood pressure lowering effect of AN, observed in the in vivo studies.     

Pharmacological basis for the use of Fumaria indica in constipation and diarrhea

The crude extract of Fumaria indica whole plant (Fi.Cr) and its fractions were studied in vitro for spasmogenic and spasmolytic effects to rationalize some of the traditional uses. Fi.Cr (1.0-5.0 mg/mL) caused a moderate degree of atropine-sensitive spasmogenic effect in guinea-pig ileum. In spontaneously contracting rabbit jejunum, Fi.Cr (0.03-0.3 mg/mL) caused a mild spasmogenicity followed by relaxation at the higher doses. In the atropinized preparations, Fi.Cr inhibited spontaneous and K(+)-induced contractions at the similar doses (0.1-1.0 mg/mL), which suggests calcium channel blockade (CCB). CCB effect was confirmed when pretreatment of the tissue with the Fi.Cr produced a dose-dependent shift in the Ca(2+) dose-response curves to the right, similar to that produced by verapamil. Activity-directed fractionation revealed that the spasmolytic effect is concentrated in the petroleum ether fraction, while dichloromethane fraction contains both spasmogenic and spasmolytic constituents. These data indicate that the presence of cholinergic and CCB constituents in Fi.Cr may explain the respective traditional use of Fumaria indica in constipation and diarrhoea.     

The presence of cholinomimetic and calcium channel antagonist constituents in Piper betle Linn

The crude aqueous extract of Piper betle leaves (Pb.Cr) was studied for the possible presence of cholinomimetic and calcium channel antagonist constituents. Pb.Cr at doses of 1-10 mg/mL caused a moderate spasmogenic effect in isolated guinea-pig ileum and this activity was concentrated in the aqueous fraction, which was found to be about 5 times more potent. Pretreatment of the tissue with atropine (1 microM) but not hexamethonium (100 microM) completely abolished the contractile effect of the aqueous fraction indicating a cholinergic (muscarinic) mechanism. In isolated rabbit jejunum preparations Pb.Cr did not produce a significant increase in the spontaneous contractions, but instead produced a dose-dependent (0.03-3.0 mg/mL) inhibition of spontaneous activity. Activity-directed fractionation revealed that the spasmolytic action was concentrated in the ethyl acetate fraction. When tested against K(+)-induced contractions, both Pb.Cr and its ethyl acetate fraction (Pb.EtAc) caused a dose-dependent inhibition, suggesting calcium channel blockade (CCB). The potent CCB effect of the crude extract and its ethyl acetate fraction was confirmed when pretreatment of the tissue with Pb.Cr or Pb.EtAc shifted the Ca(++) dose-response curves to the right in a dose-dependent manner. These data indicate that the plant contains cholinomimetic and possible calcium channel antagonist constituents, which are concentrated in the aqueous and ethyl acetate fractions respectively. It is suggested that some of the traditional uses of this plant may be explained on the basis of these activities.     

Gut and airways relaxant effects of Carum roxburghianum

Ethnopharmacological relevance

Carum roxburghianum is traditionally used in hyperactive gastrointestinal and respiratory disorders. The present study was carried out to investigate the possible gut and airways relaxant potential of Carum roxburghianum to rationalize its folk uses.

Materials and methods

Crude extract of Carum roxburghianum (Cr.Cr) was studied in in vivo and in vitro techniques.

Results

Cr.Cr exhibited protective effect against castor oil-induced diarrhea in mice at 100–1000 mg/kg. In rabbit jejunum preparations, Cr.Cr (0.03–3.0 mg/mL) caused relaxation of spontaneous and K⁺ (80 mM)-induced contractions at similar concentrations, like papaverine. Pretreatment of tissues with Cr.Cr (0.1–1.0 mg/mL) shifted Ca⁺⁺ concentration–response curves (CRCs) to right, like verapamil. Cr.Cr (0.03 and 0.1 mg/mL) caused leftward shift of isoprenaline-induced inhibitory CRCs, similar to papaverine. In isolated guinea-pig ileum, Cr.Cr (0.01 and 0.03 mg/mL) produced rightward parallel shift of acetylcholine-curves, like atropine. Cr.Cr (1.0–30 mg/kg) caused suppression of carbachol (CCh, 100 μg/kg)-induced increase in inspiratory pressure of anaesthetized rats. In guinea-pig trachea, Cr.Cr (0.03–1.0 mg/mL) relaxed CCh and high K⁺-induced contractions, shifted isoprenaline-induced inhibitory CRCs to left at 0.1 and 0.3 mg/mL and CCh-curves parallel to right (0.01 and 0.03 mg/mL). Cr.Cr did not cause any mortality of mice up to 10 g/kg dose.

Conclusion

These results indicate that Carum roxburghianum possess combination of antidiarrheal, antispasmodic and bronchodilatory effects, which provides pharmacological basis to its traditional use in the disorders of gut and airways hyperactivity, like diarrhea, colic and asthma.     

Gastrointestinal stimulant effect of Urginea indica Kunth. and involvement of muscarinic receptors

Urginea indica Kunth. (Family; Liliaceae) was studied for its gastrointestinal stimulant effect to rationalize the traditional medicinal uses as a digestive aid, stomachic and laxative. The crude aqueous-methanol extract of Urginea indica bulb (Ui.Cr) was tested on mice and isolated gut preparations. Ui.Cr, which was tested positive for alkaloids, tannins and coumarins, increased faecal output and accelerated charcoal meal transit in mice (6-12 mg/kg, p.o.), similar to that caused by carbachol (10 mg/kg). Ui.Cr (0.01-1 mg/mL) caused a spasmogenic effect in guinea-pig ileum that was reproduced in rabbit jejunum (0.01-0.3 mg/mL) followed by relaxation at a higher concentration. Like carbachol, the stimulant effect of Ui.Cr was blocked by atropine, suggesting the activation of muscarinic receptors mediating the prokinetic effect. Ui.Cr (0.01-5.0 mg/mL) also inhibited K(+) (80 mm)-induced contraction in rabbit jejunum and shifted the Ca(2+) concentration-response curves to the right, similar to verapamil, a standard calcium channel blocker. These data, indicating the presence of a gastrointestinal stimulant effect in Urginea indica possibly mediated through a cholinergic mechanism, provide a rationale for the use of Urginea indica in indigestion and constipation. The presence of a calcium antagonist effect in the plant may help to alleviate untoward effects of the plant that may result from an excessive increase in gut motility.     

Anti-diarrheal and spasmolytic activities and acute toxicity study of Soonkijangquebo, a herbal anti-diarrheal formula

The anti-diarrheal and spasmolytic activities of Soonkijangquebo (SKJQB), a Korean herbal anti-diarrheal formulation, were subjected to pharmacological evaluation. SKJQB, at a dose of 50-200 mg/kg, inhibited castor oil-induced diarrhea in mice. The median effective dose (ED50) for the anti-diarrheal effect was 93 mg/kg. In isolated rabbit jejunum preparations, SKJQB produced a spasmolytic effect by the relaxation of spontaneous contractions in a dose-dependent manner. The median effective concentration (EC50) for the spasmolytic effect was 3.6 mg/ml. In isolated guinea pig ileum preparations, SKJQB also produced a spasmolytic effect by reduction of acetylcholine-induced contractions. When tested against calcium channel blockade in rabbit jejunum, SKJQB caused a dose-dependent rightward shift in the Ca2+ dose-response curves, similar to that produced by verapamil, a well-known calcium antagonist. In an acute toxicity study in Sprague-Dawley rats, the median lethal dose (LD50) of SKJQB was greater than 2000 mg/kg, and no pathological changes were noticed in macroscopic examination by necropsy of rats treated with SKJQB. Thus, SKJQB may be safely used as a spasmolytic as well as an anti-diarrheal agent.