Spasmolytic effect of grewia asiatica fruit extract on isolated smooth muscles is mediated via multiple pathways

Background: Grewia asiatica Linn, or phalsa, is a commonly consumed fruit in Pakistan. The fruit is employed in the traditional medicine practice of Pakistan as a smooth muscle relaxant in different gastrointestinal (GI) and cardiovascular diseases. In this investigation, we show the antispasmodic and vasorelaxant actions of Grewia asiatica fruit extract.Methods: A 70% methanolic crude extract of the plant material was prepared (Ga.Cr). Different isolated GI tissue preparations and endothelium-intact aortas from rats were utilized to observe the pharmacological actions of the extract.Results: Ga.Cr, in increasing concentrations, inhibited the spontaneously contracting rabbit jejunum. In an effort to determine the mechanism of this relaxant action, contractions were induced in jejunum and ileum tissues with K+ (80 mM). Ga.Cr was able to only partially inhibit these induced contractions indicating that the mechanism might not be completely through a blockade of Ca2+ channels (CCB). When tested on low K+-(25 mM) sustained contractions, Ga.Cr cumulatively suppressed these contractions (0.1-10 mg/ml), indicating an opening of K+ channels (KCO) as the mechanism. Cromakalim, a standard KCO, was also more specific in blocking low K+-induced contractions. For the effect in aorta tissues, Ga.Cr suppressed the agonist-induced contractions from 0.3 mg/ml to 10 mg/ml. Upon challenge with L-NAME, a nitric oxide (NO) blocker, the extract response curve shifted right, indicating vasodilation was mediated via endothelial NO.Conclusion: This study shows that GI antispasmodic and vasodilator activities of Ga.Cr may be mediated via a KCO mechanism in the GI tract and through the release of NO from vascular endothelium

Intestinal, Airway, and Cardiovascular Relaxant Activities of Thymoquinone

Thymoquinone (TQ) is a bioactive component found in many medicinal herbs. In this study, we report the smooth and cardiac muscle relaxant activities of this compound. TQ concentration dependently suppressed spontaneously contracting rabbit jejunum while also relaxed high K+-(80 mM) induced contractions in jejunum and guinea-pig ileum, indicating activity at voltage-operated Ca++ channels (VOCC). Further, TQ displaced Ca++ concentration-response curves, obtained in a Ca++-free environment, to the right, showing blockade of VOCC. Similar activity was observed with verapamil, a standard VOCC blocker. TQ also exhibited nonadrenergic relaxation of agonist-induced contractions in guinea-pig trachea. When tested in fluo-4-loaded mouse lung slices, TQ inhibited ACh-induced airway narrowing and Ca++ signalling in airway smooth muscle cells. In endothelium-intact and endothelium-denuded rat aorta, TQ inhibited high K+-induced contractions at significantly lower concentrations than phenylephrine-(PE-) (1 microM) induced contractions. Relaxation of PE-induced contractions was resistant to blockade by L-NAME and atropine. In guinea-pig atria, TQ showed noncholinergic relaxation of atrial force and rate of contractions. These data suggest smooth and cardiac muscle relaxant activity of TQ possibly mediated, in part, via blockade of VOCC. The results also justify the use of TQ containing plants in related health disorders like colic, diarrhoea, cough, and asthma

Science Across Borders: 5th Annual Natural Health Product Research Conference—March 26–29, 2008, Toronto, Canada

Canada is experiencing a growing interest in the use of alternative therapies and products particularly natural health products (NHP). In 1997, Canadians spent around C$ 2 billion on NHP. In an attempt to catch with this popularity of NHP use, Canadian researchers and administrators from academia, industry and government jointly established the Natural Health Product Research Society of Canada (NHPRS). Since its formation, NHPRS has been organizing an annual meeting which brings together world renowned researchers and experts in the area of NHP research. For 2008, the annual NHPRS meeting took place in Toronto from the 26th to 29th of March with a focus on ‘Science Across Borders: Global Natural Health Products Research’. The scientific program was spread into three days of plenary lectures and oral presentations. The different sessions containing these talks were on: ethnobotany around the world; chemical analysis of NHP; product standards and quality control; ethnomedicine; novel analytical approaches; systemic research, nutrisciences and molecular medicine; and drug development from NHP. The meeting proved to be a great success in terms of the speakers that were invited and based on the data that was presented which highlighted recent research taking place in the field of NHP not only in Canada but from many parts of the world

Studies on cardio-suppressant, vasodilator and tracheal relaxant effects of Sarcococca saligna

Sarcococca saligna is a shrub that is traditionally used for its medicinal properties in Pakistan. In this study we report the cardio-suppressant, vasodilator and tracheal relaxant activities of the aqueous-methanolic extract (Ss.Cr) of the plant. Ss.Cr, that tested positive for the presence of saponins, flavonoids, tannins, phenols, and alkaloids, exhibited a dose-dependent (0.3-5 mg/mL) negative inotropic and chronotropic effect on the isolated guinea-pig atrium which was resistant to atropine (1 microM) and aminophylline (10 microM) pretreatment. In rabbit thoracic aorta, Ss.Cr dose-dependently (0.1-3 mg/mL) relaxed the high K+ (80 mM) and phenylephrine (PE, 1 microM)-induced contractions, indicating a possible Ca++ channel blocking (CCB) effect. When tested against PE (1 microM) control peaks in normal Ca++ and Ca++-free Kreb\u27s solution, Ss.Cr exhibited dose-dependent (0.1-3 mg/mL) inhibition, being more potent in relaxing the PE responses in Ca++-free Kreb\u27s solution, thus indicating specific blockade of Ca++ release from the intracellular stores. Ss.Cr also relaxed the agonist-induced contractions in: a) rat aorta irrespective of the presence of endothelium or nitric oxide synthase inhibitor L-NAME and b) rabbit and guinea-pig tracheal strips. The data shows that Ss.Cr possesses possible Ca++ channel blocking activity which might be responsible for its observed cardio-suppressant, vasodilator and tracheal relaxant effects though more tests are required to confirm this Ca++ channel blocking effect

Pharmacological basis for the medicinal use of ginger in gastrointestinal disorders

Ginger (rhizome of Zingiber officinale) has been widely used for centuries in gastrointestinal disorders, particularly dyspepsia, but its precise mode of action has yet to be elucidated. This study was undertaken to study the prokinetic action of ginger and its possible mechanism of action. Prokinetic activity of ginger extract (Zo.Cr) was confirmed in an in vivo test when it enhanced the intestinal travel of charcoal meal in mice. This propulsive effect of the extract, similar to that of carbachol, was blocked in atropine-pretreated mice, a standard cholinergic antagonist. Likewise, Zo.Cr showed an atropine-sensitive dose-dependent spasmogenic effect in vitro as well as in isolated rat and mouse stomach fundus tissues. In atropinized tissue, it showed spasmolytic activity as shown by the inhibition of 5-HT- and K+-induced contractions. A spasmolytic effect was also observed in other gut preparations either as noncompetitive inhibition of agonist dose-response curves, inhibition of high K+(80 mM)-induced contractions, or displacement of Ca2+ dose-response curves to the right, indicating a calcium antagonist effect. Phytochemical analysis revealed the presence of saponins, flavonoids, and alkaloids in the crude extract. These data indicate that Zo.Cr contains a cholinergic, spasmogenic component evident in stomach fundus preparations which provides a sound mechanistic insight for the prokinetic action of ginger. In addition, the presence of a spasmolytic constituent(s) of the calcium antagonist type may explain its use in hyperactive states of gut like colic and diarrhea

Contractile Effect of Radish and Betel Nut Extracts on Rabbit Gallbladder

Raphanus sativus (abbreviated in this paper as Rs.Cr) and Areca catechu (Ac.Cr), commonly known as radish and betel nut respectively, are traditionally used in South Asia for different gastrointestinal, gallbladder, and hepatic diseases. There has not been any study to see how they modulate gallbladder contractility. We selected isolated rabbit gallbladder tissue preparations, mounted them in tissue baths containing Krebs-Henseleit solution at 37 °C, and then recorded the changes in baseline tone of the tissues upon administration of Rs.Cr and Ac.Cr. Both the extracts exhibited concentration-dependent stimulant effect on the baseline tone of gallbladder tissues, similar to carbachol, a muscarinic receptor agonist. The stimulant effect of the extract, as well as that of carbachol, was completely blocked in the presence of atropine, a muscarinic antagonist, indicating similarity in the mechanism of action of the extracts with carbachol. The result shows potential of these extracts to contract the gallbladder and to subsequently increase bile secretion, but this remains to be investigated in detail. This study justifies the traditional use of radish and betel nut in different gastrointestinal disorders

Ginger lowers blood pressure through blockade of voltage-dependent calcium channels

Ginger (Zingiber officinale Roscoe), a well-known spice plant, has been used traditionally in a wide variety of ailments including hypertension. We report here the cardiovascular effects of ginger under controlled experimental conditions. The crude extract of ginger (Zo.Cr) induced a dose-dependent (0.3-3 mg/kg) fall in the arterial blood pressure of anesthetized rats. In guinea pig paired atria, Zo.Cr exhibited a cardiodepressant activity on the rate and force of spontaneous contractions. In rabbit thoracic aorta preparation, Zo.Cr relaxed the phenylephrine-induced vascular contraction at a dose 10 times higher than that required against K (80 mM)-induced contraction. Ca2+ channel-blocking (CCB) activity was confirmed when Zo.Cr shifted the Ca2+ dose-response curves to the right similar to the effect of verapamil. It also inhibited the phenylephrine (1 microM) control peaks in normal-Ca2+ and Ca2+-free solution, indicating that it acts at both the membrane-bound and the intracellular Ca2+ channels. When tested in endothelium-intact rat aorta, it again relaxed the K-induced contraction at a dose 14 times less than that required for relaxing the PE-induced contraction. The vasodilator effect of Zo.Cr was endothelium-independent because it was not blocked by L-NAME (0.1 mM) or atropine (1 microM) and also was reproduced in the endothelium-denuded preparations at the same dose range. These data indicate that the blood pressure-lowering effect of ginger is mediated through blockade of voltage-dependent calcium channels