Presence of cholinergic and calcium channel blocking activities explains the traditional use of Hibiscus rosasinensis in constipation and diarrhoea

The aqueous-ethanolic extract of the aerial parts of Hibiscus rosasinensis Linn. (Malvaceae) was studied for the possible presence of spasmogenic and spasmolytic constituents to rationalize its traditional use in gastrointestinal disorders. The crude extract (Hr.Cr) caused a concentration-dependent (1-10mg/mL) spasmogenic effect in isolated guinea-pig ileum, which was blocked in the presence of atropine (0.1 microM). In spontaneously contracting rabbit jejunum, the plant extract exhibited a weak stimulatory effect at lower doses (0.03-0.30 mg/mL) followed by an inhibitory effect at higher doses (1.0-3.0mg/mL). Pretreatment of the tissues with atropine blocked the stimulatory effect resulting in the potentiation of the spasmolytic effect. Hr.Cr (0.03-1.0mg/mL) also showed an inhibitory effect on K(+) (80 mM)-induced contractions. The calcium channel blocking activity was confirmed when Hr.Cr shifted the Ca(2+) concentration-response curves to the right, similar to verapamil. Activity-directed fractionation revealed that the spasmolytic component(s) was separated in the ethyl acetate, while the spasmogenic in the petroleum ether fraction. The aqueous fraction exhibited a combination of weak spasmogenic and spasmolytic effects. These data indicate that the crude extract contains spasmogenic and spasmolytic constituents mediating their effect through cholinergic receptors activation and blockade of Ca(2+) influx, respectively, which may explain its traditional use in constipation and diarrhoea.     

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.     

Prokinetic and laxative activities of Lepidium sativum seed extract with species and tissue selective gut stimulatory actions

Aim of the study

To provide ethnopharmacological basis for the medicinal use of Lepidium sativum seeds in indigestion and constipation.

Materials and methods

The in vivo studies were conducted in mice, while isolated tissues of mouse, guinea-pig and rabbit were suspended in tissue bath to measure isotonic contractions.

Results

The aqueous-methanolic extract of Lepidium sativum seeds (Ls.Cr) at 30 and 100 mg/kg showed atropine-sensitive prokinetic and laxative activities in mice, which were partially sensitive to atropine. In isolated gut preparations of mouse and guinea-pig, Ls.Cr (0.1-1 mg/mL) caused a concentration-dependent stimulatory effects both in jejunum and ileum, which was blocked in the presence of atropine. In rabbit jejunum, the stimulant effect of Ls.Cr remained unchanged in the presence of atropine, pyrilamine or SB203186, while in rabbit ileum, the stimulatory effect was partially blocked by atropine. The Ls.Cr was more efficacious in gut preparations of rabbit than in guinea-pig or mouse. The phytochemical analysis of the plant extract detected alkaloids, saponins and anthraquinones as plant constituents.

Conclusion

This study showed the prokinetic and laxative effects of Lepidium sativum in mice, which were partially mediated through a cholinergic pathway. The in vitro spasmodic effect of the plant extract mediated through a similar mechanism with species and tissue-selectivity, provides a rationale for the medicinal use of the seeds of Lepidium sativum in indigestion and constipation, and suggests studying the plant extracts on more than one species to get the wider picture.     

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.     

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.     

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.     

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.     

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.     

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 Prokinetic,Laxative and Spasmodic Activities of Phyllanthus emblica in Experimental Animals

This study was aimed to provide pharmacological basis for the medicinal use of Phyllanthus emblica fruit in indigestion and constipation using the in‐vivo and in‐vitro assays. The crude extract of the dried fruits of Phyllanthus emblica (Pe.Cr) and its fractions were tested positive for alkaloids, saponins, tannins, terpenes, flavonoids, sterols and coumarins. Pe.Cr at the doses of 100 and 300 mg/kg exhibited the prokinetic and laxative activities in mice, which were found partially sensitive to atropine. In isolated guinea‐pig ileum and rabbit jejunum, the crude extract and its aqueous fraction (Pe.Aq) caused concentration‐dependent and partially atropine‐sensitive stimulatory effects followed by relaxation at higher tested concentrations, being more efficacious in guinea pig, while more potent in rabbit tissues. The petroleum fraction (0.003–0.1 mg/mL) exhibited fully atropine‐sensitive contractions in both guinea‐pig and rabbit tissues. However, the ethyl acetate and chloroform fractions (0.003–1.0 mg/mL) showed only spasmolytic activity when studied in spontaneously contracting rabbit jejunum. This study showed that the Phyllanthus emblica possesses prokinetic and laxative activities in mice along with spasmodic effect in the isolated tissues of guinea pig and rabbit, mediated partially through activation of muscarinic receptors; thus, this study provides a rationale for the medicinal use of Phyllanthus emblica fruits in indigestion and constipation. Copyright © 2012 John Wiley & Sons, Ltd.     

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.     

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.     

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.     

Calcium Channel Blocking Activity in Desmostachya bipinnata (L.) Explains its use in Gut and Airways Disorders

Desmostachya bipinnata, despite of its popular medicinal uses, has not been widely studied for its effect in diarrhea, indigestion, and asthma. The aim of the present investigation was to provide scientific rationale for these applications. The crude aqueous‐methanolic extract of D. bipinnata (Db.Cr) was evaluated through in vivo and in vitro experiments. Db.Cr (100–500 mg/kg) protected mice against castor oil–induced diarrhea, similar to loperamide. When tested on gut preparations, Db.Cr produced an atropine‐sensitive spasmogenic effect in rabbit jejunum up to 5 mg/mL, followed by a partial relaxation at 10 mg/mL. With atropine preincubation, a verapamil‐like inhibitory effect was evident against spontaneous and high K⁺ (80 mM)–induced contractions. The maximum stimulant effect was comparable with the acetylcholine‐induced maximum contraction and was similarly reproducible in guinea pig ileum. Db.Cr inhibited carbachol (1 μM)‐induced contraction in rabbit trachea but caused an atropine‐sensitive accentuation of high K⁺–induced contraction at 0.003–0.3 mg/mL followed by inhibition at 1–5 mg/mL. On activity‐directed fractionation, inhibitory effect was concentrated on organic and stimulant effect in aqueous fraction. This study, suggesting the presence of calcium antagonist activity, possibly underlying its medicinal effect in hyperactive gut and respiratory disorders, and cholinergic activity, possibly underlying its digestive effect, provides rationale for these therapeutic uses of D. bipinnata. Copyright © 2012 John Wiley & Sons, Ltd.     

Presence of cholinergic and calcium antagonist constituents in Saussurea lappa explains its use in constipation and spasm

This study was carried out to provide a scientific basis for the traditional use of Saussurea lappa, in constipation and spasms. Isolated tissue preparations were used to see if the aqueous-methanol crude extract of the S. lappa root (Sl.Cr) contains gut stimulatory and inhibitory constituents. In isolated guinea-pig ileum, a quiescent preparation, Sl.Cr caused a concentration-dependent (0.3-5.0 mg/mL) spasmogenic effect, with the maximum effect reaching 91% of the acetylcholine maximum. A further increase in concentration caused a declining effect, indicating the presence of spasmolytic constituent(s). The spasmolytic effect was more marked in the spontaneously contracting rabbit jejunum and in the atropinized preparations. The spasmolytic effect was mediated through calcium channel blocking (CCB) activity, as evident by its inhibitory effect against high K(+) (80 mm)-induced contraction and displacement of the Ca(++) concentration-response curves to the right. These data indicate that the crude extract of Sl.Cr contains gut stimulatory constituent(s) of cholinergic-type providing a scientific basis for its use in constipation. The presence of spasmolytic constituents of CCB-type more evident in the spontaneous contracting gut preparation may explain its use in spasms.     

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.     

Pharmacological Evaluation of Gut Modulatory and Bronchodilator Activities of Achyranthes aspera Linn.

Achyranthes aspera L. is traditionally used to relieve constipation, diarrhea, and asthma. Its crude extract (Aa.Cr) was evaluated through in vivo and ex vivo experiments to rationalize these medicinal uses of A. aspera and to provide their scientific basis. Aa.Cr, at 3 and 10 mg/kg, increased fecal output, similar to castor oil, whereas at 30, 100, 300, and 700 mg/kg, it protected against castor oil‐induced diarrhea in mice when administered orally. Aa.Cr caused spasmogenic effect on rabbit jejunum and guinea pig ileum preparations, which was partially inhibited by atropine while completely blocked by cyproheptadine preincubation. Aa.Cr also relaxed high K⁺ (80 mM)‐induced contraction in rabbit jejunum. Aa.Cr inhibited CCh (100 μg/kg)‐induced bronchospasm in rats, similar to aminophylline. Like dicyclomine, Aa.Cr relaxed high K⁺ and CCh (1 μM)‐induced contractions in guinea pig trachea and caused rightwards parallel shift of CCh concentration–response curves at the lower concentrations followed by non‐parallel shift at the higher concentrations. On activity‐directed fractionation, spasmogenic and spasmolytic activities of Aa.Cr were concentrated in aqueous and organic fraction, respectively. This study suggests the presence of dose‐specific laxative and antidiarrheal effects in A. aspera, possibly mediated through cyproheptadine‐sensitive receptors and dual cholinergic and calcium channel blockade, respectively. The latter combination is also a suggested mechanism underlying its bronchodilator effect. Copyright © 2017 John Wiley & Sons, Ltd.     

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 Prokinetic,Laxative, and Antidiarrheal Effects of Morus nigra: Possible Muscarinic,Ca2+ Channel Blocking,and Antimuscarinic Mechanisms

Morus nigra Linn. (black mulberry) is used in gastrointestinal ailments. This study demonstrates gut modulatory properties of M. nigra. The prokinetic, laxative, and antidiarrheal activities of M. nigra were assessed in mice, while isolated rabbit jejunum and guinea‐pig ileum were used to explore insight into mechanism(s). At 30 and 70 mg/kg, the crude extract of M. nigra (Mn.Cr) exhibited atropine‐sensitive prokinetic and laxative effects, similar to carbachol (CCh). While at higher doses (100, 300, and 500 mg/kg), Mn.Cr offered protection against castor oil‐induced diarrhea. In rabbit jejunum, Mn.Cr and its chloroform fraction inhibited CCh‐induced contractions more potently compared with high K⁺ (80 mm ). Conversely, petroleum fraction was more potent against high‐K⁺‐induced contractions. At 0.01 mg/mL, Mn.Cr caused a parallel shift in acetylcholine concentration–response curves (CRCs) followed by a non‐parallel shift at 0.03 mg/mL, similar to dicyclomine. At further tested concentrations, Mn.Cr (0.1 and 0.3 mg/mL) and petroleum fraction suppressed Ca²⁺ CRCs, similar to verapamil. In guinea‐pig ileum, Mn.Cr, its aqueous and ethyl acetate fractions exhibited atropine‐sensitive gut stimulant activity along with additional uncharacterized excitatory response in the aqueous fraction only. These results suggest that black mulberry possesses prokinetic, laxative, and antidiarrheal effects, putatively mediated through cholinomimetic, antimuscarinic, and Ca²⁺ antagonist mechanisms, respectively. Copyright © 2016 John Wiley & Sons, Ltd.     

Pharmacological Basis for Medicinal Use of Lens culinaris in Gastrointestinal and Respiratory Disorders

Crude extract of Lens culinaris (Lc.Cr), which tested positive for presence of anthraquinones, flavonoids, saponins, sterol, tannins, and terpenes exhibited protective effect against castor oil‐induced diarrhea in mice at 100–1000 mg/kg. In rabbit jejunum preparations, Lc.Cr caused relaxation of spontaneous contractions at 0.03–5.0 mg/mL. Lc.Cr inhibited carbachol (CCh, 1 μM) and K⁺ (80 mM)‐induced contractions in a pattern similar to dicyclomine, but different from verapamil and atropine. Lc.Cr shifted the Ca⁺⁺ concentration‐response curves to the right, like dicyclomine and verapamil. Pretreatment of tissues with Lc.Cr (0.03–0.1 mg/mL) caused leftward shift of isoprenaline‐induced inhibitory CRCs, similar to papaverine. In guinea‐pig ileum, Lc.Cr produced rightward parallel shift of CCh curves, followed by non‐parallel shift at higher concentration with suppression of maximum response, similar to dicyclomine, but different from verapamil and atropine. Lc.Cr (3.0–30 mg/kg) caused suppression of carbachol (CCh, 100 µg/kg)‐induced increase in inspiratory pressure of anesthetized rats. In guinea‐pig trachea, Lc.Cr relaxed CCh and high K⁺‐induced contractions, shifted CCh curves to right and potentiated isoprenaline response. These results suggest that L. culinaris possesses antidiarrheal, antispasmodic, and bronchodilator activities mediated possibly through a combination of Ca⁺⁺ antagonist, anticholinergic, and phosphodiesterase inhibitory effects, and this study provides sound mechanistic background to its medicinal use in disorders of gut and airways hyperactivity, like diarrhea and asthma. Copyright © 2014 John Wiley & Sons, Ltd.