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Aims of study The present study was undertaken to validate traditional medicinal claims and to further explore pharmacological actions of four indigenous plants of Cholistan desert (Asphodelus tenuifolius, Corchorus depressus, Gisekia pharnaceoides and Salsola imbricata) in relation to gastrointestinal, respiratory and cardiovascular systems. Material and methods The dried and powdered plants materials were extracted by maceration using aqueous-ethanol as solvent to obtain crude extracts. The crude extracts, their ethyl acetate and aqueous fractions were tested for gastrointestinal, bronchodilator and cardiovascular activities; in vitro experiments were performed upon isolated tissue preparations of rabbit using standard tissue organ bath techniques and in vivo experiments were performed in mice and rats. Results The crude extract of Asphodelus tenuifolius (Cr.At) relaxed spontaneous, potassium (25 mM) and potassium (80 mM) mediated contractions in isolated jejunum preparations, while being equipotent in relaxing potassium (25 mM) and potassium (80 mM) mediated contractions, in manner similar to verapamil. Pretreatment of jejunum preparations with Cr.At or verapamil shifted calcium concentration response curves (CRCs) rightward with suppression of maximum effect. Aqueous fraction of Cr.At exhibited contractile effect upon spontaneous contractions in jejunum preparations. Oral administration of Cr.At to mice caused significant increase of charcoal meal intestinal transit at dose of 100 mg per kg; enhanced wet and total feces counts at doses of 50 and 100 mg per kg; but it significantly decreased charcoal meal intestinal transit at 500 mg per kg dose. Cr.At (300, 500 and 700 mg per kg; orally) reduced castor oil induced diarrhea in mice. In rabbit isolated tracheal preparations, Cr.At was more potent against potassium (80 mM) than carbachol (1 µM) mediated contractions and shifted carbachol CRCs rightward in non-parallel fashion. In rabbit isolated aortic preparations (endothelium denuded), Cr.At was more potent against potassium (80 mM) than phenylephrine (1 µM) mediated contractions. In isolated rabbit paired atria, Cr.At caused overall negative inotopic and chronotropic effects. Intravenous administration of Cr.At (3-30 mg per kg) to anesthetized normotensive rats produced hypotensive effect, which remained unchanged on pre-treating the animals with atropine. Spasmolytic constituents were found partitioned in ethyl acetate fraction of Cr.At, whereas aqueous fraction was found to contain spasmogenic activity. The crude extract of Corchorus depressus (Cr.Cd) relaxed spontaneous, potassium (25 mM), potassium (80 mM) and carbachol (1 µM) mediated contractions in rabbit isolated jejunum preparations; being most potent in relaxing carbachol (1 µM) mediated contractions, and equally potent in relaxing potassium (25 mM) and potassium (80 mM) mediated contractions, similar to that of dicyclomine. It shifted calcium CRCs upon jejunum preparations rightward in non-parallel manner, similar to that of dicyclomine. Aqueous fraction of Cr.Cd exhibited atropine sensitive contractile effect on spontaneous contractions of rabbit jejunum preparations. Oral administration of Cr.Cd to mice (50 and 100 mg per kg) caused significant increase in charcoal meal intestinal travel, enhanced formation of wet and total stool; but at 300 and 500 mg per kg doses, it significantly decreased charcoal meal intestinal travel. It also reduced castor oil induced diarrhea in mice at oral doses of 500 and 700 mg per kg. In isolated tracheal preparations, Cr.Cd was more potent in relaxing carbachol (1 µM) than potassium (80 mM) mediated contractions and shifted carbachol CRCs rightward, similar to that of dicyclomine. In isolated rabbit aorta, Cr.Cd relaxed potassium (80 mM) mediated contractions. In isolated rabbit paired atria, Cr.Cd was found to possess atropine sensitive cardio-depressant activity. Intravenous administration of Cr.Cd (1-30 mg per kg) to anesthetized normotensive rats produced hypotensive effect, which was reversed upon pre-treating animals with atropine. Gisekia pharnaceoides extract (Cr.Gp) and its ethyl acetate fraction caused preferential inhibition of potassium (25 mM) than potassium (80 mM) mediated contractions in rabbit isolated jejunum, tracheal and aortic preparations; which was attenuated in presence of glibenclamide (3 µM), in a manner similar to that of cromakalim. The aqueous fraction of Cr.Gp produced contractions on baseline of rabbit jejunum, tracheal and aortic preparations; which were attenuated subsequent to pre-incubation of tissues with caffeine (10 mM). Cr.Gp was found to possess glibenclamide sensitive cardio-depressant effects upon spontaneously beating rabbit paired atria. Oral administration of Cr.Gp to mice (50 and 100 mg per kg) resulted significant inhibition of castor oil induced diarrhea as well as significant decrease in charcoal meal intestinal travel; but at higher doses (300 and 500 mg per kg), it significantly increased charcoal meal intestinal travel and increased formation of diarrheal feces in normal mice. Intravenous administration of Cr.Gp (1-30 mg per kg) to anesthetized normotensive rats produced hypotensive effect. The crude extract of Salsola imbricata (Cr.Si) relaxed spontaneous, potassium (25 mM), potassium (80 mM) and carbachol (1 µM) mediated contractions in smooth muscle preparations of rabbit isolated jejunum. Pretreatment of tissue preparations with Cr.Si shifted calcium CRCs toward right with suppression of maximum effect, in a manner similar to verapamil. Pretreatment of tissue with propranolol (1 µM) partially antagonized the relaxant activity of the extract upon carbachol mediated contractions, similar to that of isoprenaline. Oral administration of Cr.Si (100, 300 and 500 mg per kg) in mice caused inhibition of charcoal meal intestinal travel and prevented castor oil induced diarrhea. In smooth muscle preparations of rabbit isolated trachea, Cr.Si relaxed potassium (80 mM) and carbachol (1 µM) mediated sustained contractions equipotently; shifted carbachol CRCs rightward in non-parallel fashion; and propranolol (1 µM) decreased its relaxant effect upon carbachol (1 µM) mediated contractions. In isolated aortic preparations, the Cr.Si caused doxazosin sensitive contractions upon baseline tension and relaxed potassium (80 mM) mediated contractions. Cr.Si demonstrated cardiotonic activity upon spontaneously beating paired atria, which was reversed in presence of propranolol (1 µM). Intravenous administration of Cr.Si (1-30 mg per kg) to normotensive anesthetized rats produced dose dependent hypertensive effect, which was blocked in co-presence of propranolol and doxazosin. Calcium channel blocking constituents were found to be concentrated in ethyl acetate fraction, whereas aqueous fraction of Cr.Si was found responsible for aortic contractions. The crude extracts, when administered orally to rats, increased urine and urinary electrolytes (Na+, K+ and Cl-) excretion to different extent. Conclusion The study concludes that Cr.At, Cr.Cd and Cr.Gp possess gut modulatory, bronchorelaxant, hypotensive and diuretic activities; whereas Cr.Si was found to exhibit gut relaxant, bronchorelaxant, hypertensive and diuretic activities. Possible mechanisms responsible for the observed pharmacological activities of the extracts include, but not limited to, calcium channel blocking mechanism in Asphodelus tenuifolius; calcium channel blocking, muscarinic and antimuscarinic mechanisms in Corchorus depressus; ATP dependent potassium channel opening and calcium channel blocking mechanisms in Gisekia pharnaceoides; and calcium channel blocking and adrenergic receptors agonistic mechanisms in Salsola imbricata. The study validated some of the ethnic medicinal claims of the plants along with mechanistic background.
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