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

Pharmacological explanation for medicinal use of St. John's wort in the hypo-motility disorder of gut

St. John's wort (Hypericum perforatum) is widely used in traditional medical system as a laxative agent against gastrointestinal hypo-motility disorders, such as constipation. The present research was carried out to rationalize its therapeutic potential in constipation. St. John's wort aqueous extract (Sw.Aq), which tested positive for presence of flavonoids, saponins and tannins caused concentration-dependent (1.0-10 mg/mL) contractile effect in the isolated rabbit jejunum preparations. Pretreatment of tissues with atropine (0.1 µM) abolished the stimulatory effect of Sw.Aq, suggesting that the spasmogenic effect of St. John's wort is mediated possibly through muscarinic receptor activation. In the in-vivo studies, Sw.Aq exhibited laxative effect, reflected by increase in number of mice feces. These results indicate that Sw.Aq causes gut stimulation, via cholinergic mechanism and thus provides pharmacological basis for its medicinal use in gut hypo-motility disease, constipation.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Vasodilator effect of 1-trifluoromethoxyphenyl-3-(1- propionylpiperidin-4-yl) urea is predominantly mediated through activation of voltage-dependent K+ channels

Purpose: To determine the mechanism of vasorelaxant effect of 1-trifluoromethoxyphenyl – 3 -(1-propionylpiperidin–4-yl) urea (TPPU) in cardiovascular diseases, including hypertension.Methods: Isolated rat thoracic aortic tissue preparations were mounted in an organ bath set up integrated with isometric transducer and a Power Lab assembly. TPPU (0.3 - 100 μM) was tested for vasorelaxant effect against low K+ (25 mM) and high K+ (80 mM)-induced contractions and its mechanism was determined in the presence of different antagonists (glibenclamide, 4- aminopyridine and tetraethyl ammonium).Results: In rat aortic preparations, TPPU showed a concentration-dependent (0.3 – 100 μM) and significant (p < 0.001) inhibition of low K+ induced contractions with complete inhibition obtained at 100 μM. TPPU produced significant (p < 0.05) inhibition of high K+ induced contractions with maximum relaxation of 15.36 ± 1.95 % and 15.85 ± 3.35 % at 30 and 100 μM, respectively. Glibenclamide (Gb,10 μM) pretreatment partially inhibited the vasorelaxant effect of TPPU against low K+ in a concentration range of 1 - 30 μM. 4-Aminopyridine (4-AP, 1 mM) and tetraethyl ammonium (TEA, 10 mM), markedly inhibited the vasorelexant effect of TPPU against low K+ induced contractions with maximum relaxation of 20.09 ± 2.40 and 21.67 ± 0.88 %, respectively, at 100 μM.Conclusion: TPPU possesses marked vasorelaxant properties which provides sound pharmacological evidence for its use as a potential drug candidate in the management of hypertension.Keywords: 1-Trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea, Hypertension, vasodilator, K+- channel activation, Ca+- channel antagonis

Blood Pressure Lowering Effect of Morus alba is Mediated Through Ca++ Antagonist Pathway

Morus alba has been used in traditional medicine system for the treatment of hypertension. Our objective was to provide scientific basis for the medicinal use of M. alba in hypertension. The crude extract of Morus alba (Ma.Cr) induced a dose-dependent (10-100 mg kg-1) fall in the arterial BP in anaesthetized rats. In isolated guinea-pig atria, Ma.Cr caused inhibition of atrial force and rate of spontaneous contractions, similar to that exhibited by verapamil. When tested in rat aortic ring preparations, Ma.Cr at concentration range of 0.1-10 mg mL-1 relaxed high K+ (80 mM) and phenylephrine (PE, 1 μM)-induced contractions and shifted the Ca++ dose-response curves to right, like caused by verapamil. These data indicate that the blood pressure lowering action of Morus alba occurred via., Ca++ channel blockade pathway, which provides evidence for the pharmacological basis to justify its effectiveness in hypertension

Gut and airways relaxant effects of Carum roxburghianum

Ethnopharmacological relevance: Comm 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 mu g/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

Blood pressure lowering, vasodilator and cardiac-modulatory potential of Carum roxburghianum seed extract

In current study, we describe blood pressure (BP)-lowering, endothelium-dependent, and independent vasodilator and cardio-modulatory actions of Carum roxburghianum seed. The crude extract of C. roxburghianum seed (Cr.Cr) induced dose-dependent (10-100mg/kg) fall in arterial BP of anaesthetized rats. In isolated rabbit aorta, Cr.Cr (0.3-10mg/mL) inhibited high K+ (80mM) and phenylephrine (PE, 1M)-induced contractions, like verapamil and papaverine. In endothelium-intact rat aortic preparations, Nomega-nitro-L-arginine methyl ester hydrochloride-sensitive vasodilator activity was observed with Cr.Cr, which also relaxed endothelium-denuded aorta tissues. In guinea-pig atria, Cr.Cr initially caused mild cardiac stimulation, followed by inhibition, as shown by papaverine. These results reveal that cardiovascular effects of C. roxburghianum seed extract are mediated possibly through combination of Ca++ antagonist, nitric oxide modulating and phosphodiesterase inhibitory mechanisms, though further in-depth studies are required for elucidating precise mode of action

Pharmacological explanation for medicinal use of St. John’s Wart in the hypo-motility disorder of gut.

SUMMARY. St. John’s wort (Hypericum perforatum) is widely used in traditional medical system as a laxative agent against gastrointestinal hypo-motility disorders, such as constipation. The present research was carried out to rationalize its therapeutic potential in constipation. St. John’s wort aqueous extract (Sw.Aq), which tested positive for presence of flavonoids, saponins and tannins caused concentration-dependent (1.0-10 mg/mL) contractile effect in the isolated rabbit jejunum preparations. Pretreatment of tissues with atropine (0.1 μM) abolished the stimulatory effect of Sw.Aq, suggesting that the spasmogenic effect of St. John’s wort is mediated possibly through muscarinic receptor activation. In the in-vivo studies, Sw.Aq exhibited laxative effect, reflected by increase in number of mice feces. These results indicate that Sw.Aq causes gut stimulation, via cholinergic mechanism and thus provides pharmacological basis for its medicinal use in gut hypo-motility disease, constipation

Antidiarrheal and antispasmodic activities of Vitex negundo 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 EC50 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)

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

Cardiovascular inhibitory properties of Lens culinaris

In present study, we report the blood pressure lowering, vasodilatory and cardio-depressant activities of Lens culinaris. The crude extract of L. culinaris induced dose-dependent (3-30 mg/kg) fall in the arterial pressure of rats under anesthesia. When tested in rat aortic ring preparations, L. culinaris at concentration range of 0.03-5.0 mg/mL relaxed high K+ (80 mM) and phenylephrine (1 μM)-induced contractions, like that caused by verapamil. In isolated guinea-pig atria, L. culinaris caused inhibition of atrial force and rate of spontaneous contractions, similar to that exhibited by verapamil. These data indicate that L. culinaris exhibits blood pressure lowering potential, mediated possibly through Ca++ channel blockade mechanism