Isolated Rabbit Jejunum Preparations Research Articles

In-vitro and in-vivo validation of ethnopharmacological uses of methanol extract of Isodon rugosus Wall. ex Benth. (Lamiaceae)

BackgroundIsodon rugosus is used in folk Pakistan traditional practices to cure ailments related to gastrointestinal, respiratory and cardiovascular problems. Present study was undertaken to validate these folkloric uses.MethodsA crude methanol extract of the aerial parts of Isodon rugosus (Ir.Cr.) was used for both in vitro and in vivo experiments. The plant extract was tested on isolated rabbit jejunum preparations for possible presence of spasmolytic activity. Moreover, isolated rabbit tracheal and aorta preparations were used to ascertain the relaxant effects of the extract. Acetylcholinesterase and butyrylcholinesterase inhibitory activities of Ir.Cr were also determined as well as its antioxidant activity. The in vivo antiemetic activity of the extract was evaluated by using the chick emesis model, while the analgesic and antipyretic activities were conducted on albino mice.ResultsThe application of the crude extract of I. rugosus to isolated rabbit jejunum preparations exhibited relaxant effect (0.01-0.3 mg/ml). The Ir.Cr also relaxed K+(80 m M)-induced spastic contractions in isolated rabbit jejunum preparations and shifted the Ca+2 concentration response curves towards right (0.01-0.3 mg/ml). Similarly, the extract, when applied to the isolated rabbit tracheal preparations relaxed the carbachol (1 M)- as well as K+ (80 mM)-induced contractions in a concentration range of 0.01-1.0 mg/ml. Moreover, it also relaxed (0.01-3.0 mg/ml) the phenylephrine (1 M)- and K+ (80 mM)-induced contractions in isolated rabbit aorta preparations. The Ir.Cr (80 mg/kg) demonstrated antipyretic activity on pyrogen-induced pyrexia in rabbits as compared to aspirin as standard drug. The Ir.Cr also exhibited anti-oxidant as well as inhibitory effect on acetyl- and butyryl- cholinesterase and lipoxygenase (0.5 mg/ml).ConclusionsThe observed relaxant effect on isolated rabbit jejunum, trachea and aorta preparations caused by Ir.Cr is possibly to be mediated through Ca+2 channel blockade and therefore may provided scientific basis to validate the folkloric uses of the plant in the management of gastrointestinal, respiratory and cardiovascular ailments. The observed antioxidant activity as well as the lipoxygenase inhibitory activity may validate its traditional use in pain and inflammations.

Antispasmodic and antidiarrheal activities of rhizomes of Polygonatum verticillatum maneuvered predominately through activation of K+ channels

Polygonatum verticillatum has traditionally been used for various purposes. The present study was aimed to validate the antispasmodic and antidiarrheal properties of crude methanolic extract of rhizomes of P. verticillatum (PR). Isolated rabbit jejunum preparations were suspended in tissue baths to measure the isotonic responses using Power Lab data acquisition system for the antispasmodic activity of PR, while the antidiarrheal activity was conducted in vivo in mice. PR caused complete relaxation of the spontaneous contractions of isolated rabbit jejunum preparations in a dose-dependent mode. A complete inhibition was observed against low potassium (K(+); 25 mM)-induced contractions, while the plant extract partially inhibited the high K(+)(80 mM)-induced contractions. From a mechanistic point of view, the spasmolytic effect of PR against low K(+)was antagonized by glibenclamide similar to the effect of cromakalim, thus showing the presence of constituents in PR mediating spasmolytic activity predominantly through the activation of adenosine triphosphate-sensitive K(+)channels. When tested against castor oil-induced diarrhea in mice, oral administration of the plant extract manifested marked antidiarrheal activity at the doses of 500 and 1000 mg/kg similar to loperamide. This study provided a pharmacological basis for the medicinal use of PR in abdominal colic and diarrhea.

Chemical Analysis and Calcium Channel Blocking Activity of the Essential Oil of Perovskia abrotanoides

The aim of this study was to investigate the chemical composition and provide a pharmacological base for the medicinal use of the essential oil of Perovskia abrotanoides (Pa.Oil) in gastrointestinal disorders, such as colic. The chemical investigation resulted in the identification of 26 compounds, of which tricyclene, beta-trans-ocimene, terpinene-4-acetate, terpinen-4-ol, caran-3beta-ol, linalyl acetate, beta-caryophyllene oxide and alpha-elemene had not previously been reported from P. abrotanoides. Major constituents were 1,8-cineol and delta-3-carene, which constituting 50% of the oil. In the isolated rabbit jejunum preparation Pa.Oil caused inhibition of spontaneous and high K+ (80 mM)-induced contractions, with respective EC50 values of 0.13 (0.08-0.20; n = 4) and 0.90 mg/mL (0.50-1.60; n = 5), thus showing that spasmolytic activity is mediated possibly through calcium channel blockade (CCB). The CCB activity was confirmed when pre-treatment of the tissue with Pa.Oil (0.03-0.1 mg/mL) caused a rightward shift in the Ca++ concentration-response curves, similar to that caused by verapamil, a standard calcium channel blocker. These data indicate that the essential oil of P. abrotanoides possesses spasmolytic activity mediated possibly through inhibition of voltage-dependent calcium channels, which may explain its medicinal use in colic and possibly diarrhea.

Antidiarrheal and antispasmodic activities of <i>Vitex negundo</i> are mediated through calcium channel blockade

Vitex negundo has reputation in the traditional medicine in diarrhea and gut spasm. This study was carried out to provide possible pharmacological basis to its medicinal use in hyperactive gut disorders. In castor oil-induced diarrheal model, the crude extract of V. negundo , caused a dose-dependent protection (53-71%), similar to loperamide. In isolated rabbit jejunum preparation, V. negundo caused inhibition of spontaneous and high K + -induced contractions, with EC 50 values of 0.36 (0.22-0.61) and 1.30 mg/mL (0.27-5.89; n=4-5), respectively, suggestive of spasmolytic activity, mediated possibly through calcium channel blockade (CCB). The CCB activity was further confirmed when pre-treatment of the tissue with V. negundo (0.03-0.3 mg/mL) caused a rightward shift in the Ca ++ concentration-response curves (CRCs), similar to diltiazem or loperamide. These data indicate that the antidiarrheal and spasmolytic effects of the crude extract of V. negundo are mediated through the presence of CCB-like constituent(s). DOI: http://dx.doi.org/10.3329/bjp.v8i3.15296 Bangladesh Journal of Pharmacology Vol.8(3) 2013 317-322

Pharmacological Effects ofLactuca serriolaL. in Experimental Model of Gastrointestinal, Respiratory, and Vascular Ailments

Lactuca serriola L. has traditionally been used in folkloric medicine to manage respiratory, gastrointestinal, and multiple other ailments. The present study was undertaken to explore the effect of methanol extract of L. serriola on isolated rabbit tissue preparations, that is, jejunum, trachea, and aorta in an attempt to validate its folkloric use in traditional medicine for gastrointestinal, respiratory, and vascular ailments. The application of the methanol extract to isolated rabbit jejunum preparations exhibited concentration-dependent spasmogenic effect (0.03 to 3.0 mg/mL), but interestingly further increase in concentration (5.0 mg/mL) resulted in complete spasmolytic effect. The pretreatment of the tissue preparations with atropine (0.1 μM) caused the suppression of the contractile response. Moreover, the same extract also caused relaxation of K+-(80 mM) induced spastic contractions of isolated rabbit jejunum preparations (5.0 mg/mL) and shifted the Ca++ dose response curves towards right at concentration range of 0.3–1.0 mg/mL. Similarly, the extract application to isolated rabbit tracheal preparations relaxed the carbachol-(1 μM) induced (0.3–1.0 mg/mL) as well as K+-(80 mM) induced contractions (3.0 mg/mL). Furthermore, it relaxed the phenylephrine (1 μM)-induced contractions in isolated rabbit aorta preparations (3.0 mg/mL) and K+ (80 mM)-induced contractions (1.0 mg/mL). These effects were found comparable to that of dicyclomine, as an antagonist of muscarinic receptors as well as a possible Ca++ channel blocker. The previously mentioned findings may partially justify the folkloric use of Lactuca serriola in the management of conditions pertaining to spasm of intestine, bronchioles, and vasculature.

Pharmacological Evaluation ofProsopis cineraria(L.) Druce in Gastrointestinal, Respiratory, and Vascular Disorders

In this paper, a crude methanolic extract from the stem bark of Prosopis cineraria, a plant native of Pakistan, was tested for its possible presence of spasmolytic, bronchodilator, and vasodilator activities in an attempt to validate some of its folkloric uses. Moreover, attempts were made to provide plausible explanations of the observed biological activities. The extract caused relaxation of the spontaneous as well as K+ (80 mM)-induced contractions at tissue bath concentrations of 3–10 mg/mL in isolated rabbit jejunum preparations, probably mediated through blockade of Ca+2 channels. This finding was further confirmed by the shifting of the Ca+2 concentration response curves to the rightward in a manner similar to verapamil used as a standard Ca+2 channel blocker. The extract also exhibited nonspecific relaxant effect on carbachol (1 μM)- and K+ (80 mM)-induced contractions in isolated rabbit tracheal preparations. The same effect was recorded for phenylephrine (11 μM) and K+ (80 mM)-induced contractions in isolated rabbit aortic preparations in a manner similar to verapamil. These observations confirm that observed bronchodilator and vasodilator activities were possibly mediated through blockade of Ca+2 channels. The above-mentioned observations validate the traditional use of the plant in the treatment of respiratory and gastrointestinal ailments.

Pharmacological basis for the medicinal use of Psidium guajava leave in hyperactive gut disorders

Psidium guajava L. is reputed for its medicinal use in hyperactive gut disorders. This study was aimed to investigate mechanism responsible for its medicinal use in diarrhea and gut spasm. In castor oil-induced diarrheal model, the crude extract of P. guajava (100-1,000 mg/kg), provided 20.52-81.05% protection, similar to loperamide. In isolated rabbit jejunum preparations, crude extract was found more potent against high K + than spontaneous pre-contractions, similar to verapamil, with EC 50 values of 0.66 (0.44-0.97; n=8) and 2.28 mg/mL (1.43-3.62; n=8), respectively, suggests calcium channel blocking activity, as a possible mode of action. The Ca ++ channel blocking activity was further confirmed when pre-treatment of tissue with crude extract (0.3-1 mg/mL) caused a rightward shift in the Ca ++ concentration-response curves, similar to verapamil. Loperamide also inhibited spontaneous and high K + -induced contractions and shifted the Ca ++ curves to the right. These data indicate that crude extract of P. guajava possesses Ca ++ antagonist-like constituent(s), which explain its inhibitory effect on gut motility.

Gastrointestial and respiratory activities of Acacia leucophloea

Ethnopharmacological relevanceThe barks of Acacia leucophloea (Fabaceae) are used in Pakistan traditional medicine as an astringent, a bitter, a thermogenic, a styptic, a preventive of infections, an anthelmintic, a vulnery, a demulcent, an expectorant, an antipyretic, an antidote for snake bites and in the treatment of bronchitis, cough, vomiting, wounds, ulcers, diarrhea, dysentery, internal and external hemorrhages, dental caries, stomatitis, and intermittent fevers and skin diseases. Materials and methodsA study was carried out for the possible elucidation of mechanisms justifying the traditional medicinal uses of A. leucophloea (Fabaceae) in gastrointestinal and respiratory diseases. In vitro experiments were carried out over isolated rabbit jejunum and guinea-pig ileum in order to determine spasmolytic and bronchorelaxant activities, while in vivo studies were conducted in mice for antidiarrheal properties. ResultsA methanol crude extract of barks of the plant caused a concentration-dependent relaxation (0.1–3mg/ml) of isolated rabbit jejunum preparations in a pattern similar to that of nifedipine and dicyclomine, suggesting a Ca2+ channel-blocking mechanism in addition to an anticholinergic effect. In guinea-pig ileum the extract caused a parallel shift in the Ach-curves without suppression of maximum contractile response, followed by a non-parallel shift with the suppression of maximum contractile response at higher concentration similar to that caused by dicyclomine. Moreover, in rabbit trachea, it also caused the relaxation of carbachol (1μM) and high K+-induced contractions at a dose ranging between 0.1578 and 0.734mg/ml and 0.46–0.94mg/ml, respectively. These findings indicate that the extract possesses spasmolytic and bronchodilator activities, mediated possibly through blockade of Ca2+ channels, thus justifying its medicinal use in diarrhea and asthma. Acacia leucophloea methanol extract exhibited dose-dependent (100–500mg/ml) protective effect against castor oil induced diarrhea. ConclusionsThe data obtained contribute to the validation of the traditional use of Acacia leucophloea bark in treating gastrointestinal and respiratory disorders, providing an hypothesis on the possible mechanisms of action.

Antidiarrheal and antispasmodic activities of Vincetoxicum stocksii are mediated through calcium channel blockade

This study was carried out to explore the mechanism underlying antidiarrheal and antispasmodic activities of Vincetoxicum stocksii. The crude extract of V. stocksii provided 12-24% protection from castor oil-induced diarrhea at the dose of 300-1,000 mg/kg, similar to loperamide. In isolated rabbit jejunum preparations, V. stocksii caused inhibition of the spontaneous and high K+ (80 mM)-induced contractions, with respective EC50 values of 2.53 (1.65-3.90) and 0.95 mg/mL (0.63-1.42), similar to that caused by verapamil, suggesting the calcium channel blocking effect. Loperamide caused inhibition of spontaneous and high K+-induced contraction, with respective EC50 values of 8.59 (6.33-10.11) and 9.12 µM (7.33-12.81). The calcium channel blocking activity was further confirmed when pretreatment of the tissues with V. stocksii (1-3 mg/mL) caused a rightward displacement of the Ca++ concentrations response curves, similar to that produced by verapamil; constructed in Ca++ free medium. These data indicate that the crude extract of V. stocksii contains calcium channel blocking constituents that may possibly explain its medicinal use in hyperactive states of gut, such as, diarrhea and spasms.

Antibacterial, antifungal, antispasmodic and Ca++ antagonist effects of Caesalpinia bonducella

Caesalpinia bonducella F. (Leguminosae) has been used as a folk medicine for a variety of ailments. The crude extract of C. bonducella and its fractions were studied for antibacterial, antifungal, antispasmodic and Ca++ antagonistic properties. The strongest antibacterial effect was displayed by the n-butanol (72%) and ethyl acetate (80%) fractions, followed by the crude extract (46% and 42%), against Escherichia coli and Bacillus subtilis, respectively. The plant extract and its fractions showed mild to excellent activity in antifungal bioassays, with maximum antifungal activity against Candida glaberata (80%) and Aspergillus flavus (70%) by the n-butanol and chloroform fractions, followed by the crude extract (70% and 65%). Caesalpinia bonducella extract caused concentration-dependent inhibition of spontaneous and high K+ (80 mM)-induced contractions of isolated rabbit jejunum preparations, similar to that caused by Verapamil. These results indicate that C. bonducella exhibits antibacterial, antifungal, spasmolytic and Ca++ channel blocking actions.

Calcium channel blocking activity of Mentha longifolia L. explains its medicinal use in diarrhoea and gut spasm

Mentha longifolia has a reputation in traditional medicine in the indications of diarrhoea and gut spasm. This study was carried out to provide a possible pharmacological basis for its medicinal use in hyperactive gut disorders. In a castor oil induced diarrhoeal model, the crude extract of Mentha longifolia (Ml.Cr), at doses of 100-1000 mg/kg, provided 31-80% protection, similar to loperamide. In isolated rabbit jejunum preparations, Ml.Cr caused inhibition of spontaneous and high K(+)-induced contractions, with respective EC50 values of 1.80 (1.34-2.24; n = 6-8) and 0.60 mg/mL (0.37-0.85; n = 6-8), which suggests spasmolytic activity, mediated possibly through calcium channel blockade (CCB). The CCB activity was further confirmed when pretreatment of the tissue with Ml.Cr (0.3-1 mg/mL) caused a rightward shift in the Ca(++) concentration-response curves (CRCs), similar to verapamil. Loperamide also inhibited spontaneous and high K(+)-induced contractions and shifted the Ca(++) CRCs to the right. Activity-directed fractionation revealed that the petroleum spirit fraction was more potent than the parent crude extract and aqueous fraction. These data indicate that the antidiarrhoeal and spasmolytic effects of the crude extract of Mentha longifolia are mediated through the presence of CCB-like constituent(s), concentrated in the petroleum spirit fraction and this study provides indirect evidence for its medicinal use in diarrhoea and spasm.

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 microM) 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 microM) and high K(+)-induced contractions. These results indicate that Ho.Cr possesses gastrointestinal, respiratory and cardiovascular inhibitory effects, mediated via a Ca(++) antagonist mechanism.

Antispasmodic and vasodilator activities of Morinda citrifolia root extract are mediated through blockade of voltage dependent calcium channels

BackgroundMorinda citrifolia (Noni) is an edible plant with wide range of medicinal uses. It occurs exclusively in tropical climate zone from India through Southeast Asia and Australia to Eastern Polynesia and Hawaii. The objective of this study was to explore the possible mode(s) of action for its antispasmodic, vasodilator and cardio-suppressant effects to rationalize its medicinal use in gut and cardiovascular disorders.MethodsIsolated tissue preparations such as, rabbit jejunum, rat and rabbit aorta and guinea pig atria were used to test the antispasmodic and cardiovascular relaxant effects and the possible mode of action(s) of the 70% aqueous-ethanolic extract of Morinda citrifolia roots (Mc.Cr).ResultsThe Mc.Cr produced a concentration-dependent relaxation of spontaneous and high K+ induced contractions in isolated rabbit jejunum preparations. It also caused right ward shift in the concentration response curves of Ca++, similar to that of verapamil. In guinea-pig right atria, Mc.Cr caused inhibition of both atrial force and rate of spontaneous contractions. In rabbit thoracic aortic preparations, Mc.Cr also suppressed contractions induced by phenylephrine (1.0 μM) in normal- Ca++ and Ca++-free Kerb's solutions and by high K+, similar to that of verapamil. In rat thoracic aortic preparations, Mc.Cr also relaxed the phenylephrine (1.0 μM)-induced contractions. The vasodilatory responses were not altered in the presence of L-NAME (0.1 mM) or atropine (1.0 μM) and removal of endothelium.ConclusionsThese results suggest that the spasmolytic and vasodilator effects of Mc.Cr root extract are mediated possibly through blockade of voltage-dependent calcium channels and release of intracellular calcium, which may explain the medicinal use of Morinda citrifolia in diarrhea and hypertension. However, more detailed studies are required to assess the safety and efficacy of this plant.

Antidiarrhoeal and spasmolytic activities of the methanolic crude extract of Alstonia scholaris L. are mediated through calcium channel blockade

This study was aimed to provide a pharmacological basis to the medicinal use of Alstonia scholaris as an antidiarrhoeal and antispasmodic by using in vivo and in vitro techniques. In the in vivo study the crude extract of Alstonia scholaris (As.Cr), which tested positive for the presence of alkaloids, provided 31-84% protection against castor oil-induced diarrhoea in mice at 100-1000 mg/kg doses, similar to loperamide. In isolated rabbit jejunum preparation, the As.Cr caused inhibition of spontaneous and high K(+) (80 mm)-induced contractions, with respective EC(50) values of 1.04 (0.73-1.48) and 1.02 mg/mL (0.56-1.84; 95% CI), thus showing spasmolytic activity mediated possibly through calcium channel blockade (CCB). The CCB activity was further confirmed when pretreatment of the tissue with the As.Cr (0.3-1 mg/mL) caused a rightward shift in the Ca(++) concentration-response curves similar to verapamil, a standard calcium channel blocker. Loperamide also inhibited spontaneous and high K(+) precontractions as well as shifted the Ca(++) CRCs to the right. These results indicate that the crude extract of Alstonia scholaris possesses antidiarrhoeal and spasmolytic effects, mediated possibly through the presence of CCB-like constituent(s) and this study provides a mechanistic base for its medicinal use in diarrhoea and colic.

Insight into the possible mechanism of antidiarrheal and antispasmodic activities of piperine

Piperine is a piperidine-ring containing alkaloid and a major constituent of Piper nigrum Linn. and Piper longum Linn. species, belonging to the Piperaceae family. The present study explored their mode of action in gastrointestinal disorders, such as diarrhea and colic. Piperine at the dose of 10 mg/kg provided complete protection from castor oil-induced diarrhea in mice, similar to that of loperamide. In isolated rabbit jejunum preparations, piperine exhibited concentration-dependent inhibition of spontaneous contractions with an EC50 value of 149.1 μM (89.26–249.20, 95% CI). When used to treat high K+ (80 mM)-induced sustained contractions, piperine inhibited such contractions with an EC50 value of 80.86 μM (56.10–116.50, 95% CI), which suggested a calcium channel blocking (CCB) effect. The CCB effect was further confirmed when pretreatment of the tissues with piperine (10–100 μM) caused a rightward shift in the Ca++ concentration–response curves (CRCs) in Ca++-free medium, similar to that caused by verapamil. Loperamide also caused the inhibition of spontaneous and high K+-induced contractions as well as shifted the Ca++ CRCs to the right at concentrations of 1–10 μM. These data indicate that piperine exhibits antidiarrheal and antispasmodic activities, mediated possibly through calcium channel blockade.

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 (0.1–3.0 mg/mL) produced relaxation of spontaneous and low K + (25 mM)-induced contractions with negligible effect on high K + (80 mM) 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 0.12 mg/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.

Studies on antihypertensive and antispasmodic activities of Andropogon muricatus Retz.This article is one of a selection of papers published in this special issue (part 1 of 2) on the Safety and Efficacy of Natural Health Products.

The aqueous-methanolic crude extract of Andropogon muricatus (Am.Cr) was investigated pharmacologically to determine some of its medicinal uses in cardiovascular and gastrointestinal disorders. A series of in vivo and in vitro studies were conducted to evaluate dose-dependent effects of Am.Cr on mean arterial pressure (MAP), cardiac and vascular contractions, and to further investigate the potential mechanism of action. Intravenous administration of Am.Cr (10-50 mg/kg) caused a fall (18%-56%) in MAP in normotensive rats under anesthesia. When tested in isolated guinea pig atria, Am.Cr (0.03-5.0 mg/mL) exhibited a cardiodepressant effect on the rate and force of spontaneous contractions. In isolated rabbit aorta, Am.Cr caused inhibition of K+ (80 mmol/L)-induced contractions at a lower concentration than of phenylephrine. In isolated rabbit jejunum preparations, Am.Cr (0.01-0.10 mg/mL) caused relaxation of spontaneous and high K+ (80 mmol/L)-induced contractions, suggesting that the spasmolytic effect is mediated possibly through calcium channel blockade (CCB). The CCB activity was confirmed when pretreatment of the tissue with Am.Cr (0.03-0.1 mg/mL) shifted the Ca2+ dose-response curves to the right, similar to that caused by verapamil. These data indicate that the blood pressure-lowering and spasmolytic effects of Am.Cr are mediated possibly through a calcium channel blocking activity. Phytochemical screening of Am.Cr revealed the presence of phenols, saponins, tannins, and terpenes, which may be responsible for the observed vasodilator, cardiodepressant, and antispasmodic activities. This study shows potential with respect to its medicinal use in cardiovascular and gut disorders.

Pharmacological basis for the use of Borago officinalis in gastrointestinal, respiratory and cardiovascular disorders

Aim of the study In this study, we investigated the crude extract of Borago officinalis leaves (Bo.Cr) for its antispasmodic, bronchodilator, vasodilator and cardio-depressant activities to rationalize some of the traditional uses. Materials and methods Bo.Cr was studied using different isolated tissue preparations including rabbit jejunum, trachea, aorta, and guinea-pig atria. Results Bo.Cr which was tested positive for flavonoids, coumarins, sterols and tannins produced a concentration-dependent relaxation of spontaneous and K+ (80 mM)-induced contractions in isolated rabbit jejunum preparations, suggestive of Ca++ antagonist effect, which was confirmed when pretreatment of the tissue with Bo.Cr produced a rightward shift in the Ca++ concentration-response curves like that caused by verapamil. In rabbit tracheal preparations, Bo.Cr relaxed the carbachol (1 μM) and K+-induced contractions. Verapamil also produced non-specific inhibitory effect. In rabbit aorta preparations, Bo.Cr exhibited vasodilator effect against phenylephrine and K+-induced contractions similar to verapamil. When tested in guinea-pig atria, Bo.Cr caused inhibition of both atrial force and rate of contractions. Conclusions These results suggest that the spasmolytic effects of Bo.Cr are mediated possibly through Ca++ antagonist mechanism, which might explain the traditional use of Borago officinalis in hyperactive gastrointestinal, respiratory and cardiovascular disorders.

The analgesic, anti-inflammatory and calcium antagonist potential ofTanacetum artemisioides

Several species of the genus Tanacetum are traditionally used in a variety of health conditions including pain, inflammation, respiratory and gastrointestinal disorders. In the current investigation, we evaluated the plant extract of T. artemisioides and some of its pure compounds (flavonoids) for analgesic, anti-inflammatory and calcium antagonist effects in various in-vivo and in vitro studies. Using the actetic acid induced writhing test, intraperitoneal (i.p) administration of the plant extract (25-50 mg/kg) and its flavonoid compounds TA-1 and TA-2 (1-5 mg/kg ) exhibited significant analgesic actvity. The maximum analgesic effect observed with the crude extract of the plant was 71% at 50 mg/kg, while that of compounds TA-1 and TA-2 (5 mg/kg i.p) was 75 and 47%, respectively. The plant extract and its pure compounds caused inhbition of formalin induced paw licking in mice predominatly in the second phase of the test. Diclofenac sodium, a standard reference compound, showed a simlar effect in these chemical induced pain models. In the carrgeenan induced rat paw edema assay, the plant extract (50-200 mg/kg i.p) demonstrated significant (P< 0.01) anti-inflammatory activity which was comparable to that obtained with diclofenac sodium and indomethacin. In isolated rabbit jejunum preprations the plant extract showed an atropine sensitive dose-dependent (0.10-1.0 mg/mL) spasmogenic activity followed by a spasmolytic effect at the next higher doses (3-5 mg/mL). The crude extract of the plant also inhibited the high K+-induced contractions, indicating a calcium channel blocking (CCB) activity, which was further confirmed when the plant extract caused a rightward shift in the Ca++ concentration response curves in the isolated rabbit jejunum preparations, similar to that seen with verapamil. The flavonoid compounds isolated from the plant were devoid of any activity in the isolated tissue preparations. These results indicate that the plant extract of T. artemisioides possesses analgesic, anti-inflammatory and CCB activities. The flavonoid compounds of the plant may have a role in its observed analgesic and antiinflammatory activities, while the CCB activity of the plant may be attributed to some other chemical constituents present. Moreover the findings support the traditional reputation of the genus Tanacetum for its therapeutic benefits in pain and inflammatory conditions.

Ca 2+ antagonist and cholinergic activities explain the medicinal use of olive in gut disorders

The crude extract of olive or Olea europea fruit (OeF.Cr) and its fractions were studied in vitro for the possible spasmolytic and spasmogenic activities to rationalize some of its medicinal uses. In isolated rabbit jejunum preparations, OeF.Cr caused a dose-dependent (0.1-3.0 mg/mL) relaxation of both spontaneous and K +-induced contractions. The calcium-channel blocking activity was confirmed when pretreatment of the tissue with OeF.Cr produced a dose-dependent shift in the Ca 2+ dose-response curves to the right, similar to that produced by verapamil. Apparently, OeF.Cr was found devoid of any spasmogenic effect; however, when tested in the presence of atropine, the spasmolytic effect was potentiated, indicating the presence of spasmogenic constituent(s) of cholinergic type. The presence of the spasmogenic component was confirmed when the resultant aqueous fraction (0.1-1.0 mg/mL) caused an atropine-sensitive stimulatory effect followed by relaxation at the next higher dose (3.0 mg/mL). These results indicate that olives contain spasmolytic (Ca 2+ antagonists) and spasmogenic (cholinergic) constituents, which provides a scientific base for its medicinal use in gastrointestinal disorders, such as abdominal colic, diarrhea, and constipation.