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1.  Nitric oxide pathway-mediated relaxant effect of aqueous sesame leaves extract (Sesamum radiatum Schum. & Thonn.) in the guinea-pig isolated aorta smooth muscle 
Background
Sesamum radiatum Schum. & Thonn. (Pedaliaceae) is an annual herbaceous plant, which belongs to the family Pedaliaceae and genus Sesamum. Sesame is used in traditional medicine in Africa and Asia for many diseases treatment. Sesame plant especially the leaves, seed and oil are consumed locally as a staple food by subsistence farmers. The study analyses the relaxation induced by the aqueous extract of leaves from sesame (ESera), compared with those of acetylcholine (ACh) in the guinea-pig aortic preparations (GPAPs), in order to confirm the use in traditional medicine for cardiovascular diseases.
Methods
The longitudinal strips of aorta of animals were rapidly removed from animals. The aorta was immediately placed in a Mac Ewen solution. Experiments were performed in preparations with intact endothelium as well as in aortae where the endothelium had been removed. The preparations were suspended between two L-shaped stainless steel hooks in a 10 ml organ bath with Mac Ewen solution. The isometric contractile force of the aorta strips of guinea-pig were recorded by using a strain gauge. All both drugs caused concentration-dependent relaxations responses.
Results
The aqueous extract of leaves from sesame ESera (1 × 10-7 – 0.1 μg/ml) caused a graded relaxation in GPAPs with intact endothelium, with a EC50-value of 1 × 10-4 μg/ml. The same effect was observed with ACh (7 × 10-2 nM – 7 × 10-1 μM), which caused relaxation in a concentration-dependent manner. The relaxation in response to ESera and, like that to ACh in GPAPs without endothelium, was fully abolished. Destruction of the endothelium or incubation with the nitric oxyde synthase inhibitor (L-NNA) significantly enhanced the inhibition of the relaxation response to ESera. Moreover, all concentrations induced vasoconstrictions. However, L-NNA produced a significant displacement to the right (about 65-fold) of the relaxation response to ESera. Similar results were obtained with ACh. Both diclofenac and tetra-ethyl-ammonium (TEA) pretreatment of GPAPs induced a suppression of the relaxation caused by ESera, and produced a very significant rightward shifts of the CRC (16-fold) for diclofenac and increase the Emax. In contract, the relaxation caused by ACh was not significantly affected by diclofenac or by TEA.
Conclusion
Thus, the present results indicate clearly that the nitric oxide largely contribute to the relaxation effect of Esera and of ACh in GPAPs. In addition, their contractile effects are also mediated by cyclooxygenase activation, and probably the K+ channels involvement, that confirm the use of various preparations of Esera for the treatments of cardiovascular diseases.
doi:10.1186/1472-6882-8-23
PMCID: PMC2426668  PMID: 18505582
2.  Evaluation of acute toxicity and hepatoprotective activity of the methanolic extract of Dichrostachys cinerea (Wight and Arn.) leaves 
Pharmacognosy Research  2011;3(1):40-43.
Background:
D. cinerea are the chief source of drug compounds that are active against various ailments such as jaundice, inflammations rheumatism, fever, asthma, body ache, chest problems, toothache, ulcers, wounds, eye diseases and have an aphrodisiac property. In present study, It was aimed to test the hepatoprotective activity of the plant.
Material and Methods:
The methanolic extract of Dichrostachys cinerea (Mimoseae) leaves was subjected to evaluation of acute toxicity and hepatoprotective property, using albino mice and rats. The parameters for estimation of liver function, based on serum markers such as total bilirubin, total protein, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase with histopathological profile of the liver tissue, were studied consequently.
Results:
The methanolic extract did not show any mortality up to a dose of 3500 mg/kg body weight. The methanolic extract showed significant hepatoprotectivity. The histopathological profile of the drug-treated liver tissue demonstrated similar morphology as that of controls.
Conclusions:
Methanolic extract of Dichrostachys cinerea was found to have significant hepatoprotective activity.
doi:10.4103/0974-8490.79114
PMCID: PMC3119270  PMID: 21731394
Acute toxicity; carbon tetrachloride induced; Dichrostachys cinerea; hepatoprotective
3.  Woody encroachment reduces nutrient limitation and promotes soil carbon sequestration 
Ecology and Evolution  2014;4(8):1423-1438.
During the past century, the biomass of woody species has increased in many grassland and savanna ecosystems. As many of these species fix nitrogen symbiotically, they may alter not only soil nitrogen (N) conditions but also those of phosphorus (P). We studied the N-fixing shrub Dichrostachys cinerea in a mesic savanna in Zambia, quantifying its effects upon pools of soil N, P, and carbon (C), and availabilities of N and P. We also evaluated whether these effects induced feedbacks upon the growth of understory vegetation and encroaching shrubs. Dichrostachys cinerea shrubs increased total N and P pools, as well as resin-adsorbed N and soil extractable P in the top 10-cm soil. Shrubs and understory grasses differed in their foliar N and P concentrations along gradients of increasing encroachment, suggesting that they obtained these nutrients in different ways. Thus, grasses probably obtained them mainly from the surface upper soil layers, whereas the shrubs may acquire N through symbiotic fixation and probably obtain some of their P from deeper soil layers. The storage of soil C increased significantly under D. cinerea and was apparently not limited by shortages of either N or P. We conclude that the shrub D. cinerea does not create a negative feedback loop by inducing P-limiting conditions, probably because it can obtain P from deeper soil layers. Furthermore, C sequestration is not limited by a shortage of N, so that mesic savanna encroached by this species could represent a C sink for several decades.
We studied the effects of woody encroachment on soil N, P, and C pools, and availabilities of N and P to Dichrostachys cinerea shrubs and to the understory vegetation. Both N and P pools in the soil increased along gradients of shrub age and cover, suggesting that N fixation by D. cinerea did not reduce the P supply. This in turn suggests that continued growth and carbon sequestration in this mesic savanna ecosystems are unlikely to be constrained by nutrient limitation and could represent a C sink for several decades.
doi:10.1002/ece3.1024
PMCID: PMC4020701  PMID: 24834338
Chronosequence; land cover change; N:P stoichiometry; plant–soil feedback; savanna; tree–grass interactions
4.  Pharmacological characterisation of extracts of coffee dusts. 
The contractile or relaxant activities or both of aqueous extracts of green and roasted coffees were assayed on isolated guinea pig tracheal spirals. Contractile and relaxant activities were compared with histamine and theophylline, respectively. Green coffee extracts induced concentration dependent contraction, but the maximal tension never exceeded 76.3% +/- 5.2 of a maximal histamine contraction (0.69 +/- 0.07 g/mm2 v 0.52 +/- 0.05 g/mm2; p (0.01). One gram of green coffee dust had a biological activity equivalent to 1.23 +/- 0.1 mg of histamine. The pD2 value of histamine was -5.17 +/- 0.05. The potency of green coffee was unaffected by mepyramine maleate (1 micrograms/ml, final bath concentration) while that of histamine was reduced 500 fold. Tissues contracted with histamine were not significantly relaxed by green coffee extracts. By contrast, roasted coffee extracts induced concentration dependent relaxation of uncontracted and histamine contracted tissues. Tissues contracted with green coffee extracts were also completely relaxed by roasted coffee extracts. The pD2 value of theophylline was -4.10 +/- 0.03. The relaxant activity of 1 g of roasted coffee was equivalent to 1.95 +/- 0.16 mg of theophylline. The potency of these extracts was significantly reduced after propranolol (1 micrograms/ml; dose ratio 1.56). Our results show that coffee dust extracts have considerable biological activity which changes from a contractile to a relaxant action as a consequence of processing. The greater incidence of adverse reactions to green coffee dust(s) in coffee workers may be related to the contractile activity present in green coffee dust.
PMCID: PMC1009171  PMID: 6830717
5.  Myostimulating Effect of Sesamum Radiatum Aqueous Leaf Extract in Isolated Guinea-Pig Taenia Caeci Contractile Activity 
This study was carried to examine the effects of the aqueous leaf extract of Sesamum radiatum, a laxative plant on the contractile activity of Taenia caeci, an intestinal smooth muscle. Strips of Taenia caeci were rapidly removed from guinea-pig and were suspended between two L-shaped stainless steel hooks in a 10 ml organ bath with Mac Ewen solution. The isometric contractile force of the Taenia caeci strips were recorded by using a strain gauge. S. radiatum aqueous leaf extract (ESera) is a spasmogenic substance. This myostimulant effect is characterized by the increase of the rhythm and the amplitude of isolated guinea-pig Taenia caeci smooth muscle in normal solution and by the development of contracture in modified solution and in solution without calcium. A similar effect was observed with ACh which caused a graded increase of the contractile activity of Taenia caeci. The effects induced by ESera and ACh were reversed in the presence of atropine. The spasmogenic effect induced by ESera could justify partially the use of S. radiatum as laxative in traditional medicine.
PMCID: PMC3218465  PMID: 22654214
Sesamum radiatum; acetylcholine; Taenia caeci; contractile activity
6.  Evaluation of gut modulatory and bronchodilator activities of Amaranthus spinosus Linn. 
Background
The aqueous-methanolic extract of Amaranthus spinosus (A. spinosus Linn.,) whole plant, was studied for its laxative, spasmolytic and bronchodilator activities to validate some of its medicinal uses.
Methods
The crude extract of A. spinosus was studied in-vivo for bronchodilator and laxative activities and in-vitro using isolated tissue preparations which were mounted in tissue baths assembly containing physiological salt solutions, maintained at 37°C and aerated with carbogen, to assess the spasmolytic effect and to find out the possible underlying mechanisms.
Results
In the in-vivo experiments in mice, the administration of A. spinosus increased fecal output at doses of 100 and 300 mg/kg showing laxative activity. It also inhibited carbachol-induced bronchospasm in anesthetized rats at 1, 3, 10 and 30 mg/kg indicative of bronchodilator activity. When tested on isolated gut preparations, the plant extract showed a concentration-dependent (0.01-10.0 mg/ml) spasmogenic effect in spontaneously contracting rabbit jejunum and guinea-pig ileum. The spasmogenic effect was partially blocked in tissues pretreated with atropine (0.1 μM). When tested on K+ (80 mM)-induced sustained contractions in isolated rabbit jejunum, the plant extract caused complete relaxation and also produced a shift in the Ca++ concentration-response curves (CRCs) towards right, similar to diltiazem. In rabbit trachea, the plant extract completely inhibited K+ (80 mM) and carbachol (CCh, 1 μM)-induced contractions at 1 mg/ml but pretreatment of tissue with propranolol (1 μM), caused around 10 fold shift in the inhibitory CRCs of the plant extract constructed against CCh-induced contraction. The plant extract (up to 0.3 mg/ml) also increased both force and rate of spontaneous contractions of isolated guinea-pig atria, followed by relaxation at higher concentration (1.0-5.0 mg/ml). The cardio-stimulant effect was abolished in the presence of propranolol, similar to that of isoprenaline. Activity-directed fractionation revealed that the spasmolytic component(s) was separated in the organic fraction, whereas the spasmogenic component was concentrated in the aqueous fraction.
Conclusion
These results indicate that A. spinosus possesses laxative activity partially mediated through cholinergic action. The spasmolytic effect was mediated through calcium channel blocking (CCB), while bronchodilator activity through a combination of β-adrenergic and CCB pathways, which may explain the traditional uses of A. spinosus in gut and airways disorders.
doi:10.1186/1472-6882-12-166
PMCID: PMC3545920  PMID: 23025418
Amaranthus spinosus; Laxative; Spasmolytic; Bronchodilator; Cholinergic; Ca++ antagonist
7.  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.
doi:10.1155/2012/305319
PMCID: PMC3540993  PMID: 23320027
8.  The effect of epibatidine on spontaneous and evoked neurotransmitter release in the mouse and guinea pig isolated vas deferens 
British journal of pharmacology  2007;150(7):906-912.
Summary
Background and purpose
Nicotinic agonists increase sympathetic field-stimulus-evoked contraction of the rodent vas deferens, presumably by increasing evoked neurotransmitter release. This presumption was tested in two species.
Experimental approach
The effect of the nicotinic acetylcholine receptor (nAChR) agonist epibatidine on neurotransmitter release in mouse and guinea pig isolated vas deferens was investigated using contraction studies and conventional intracellular recording techniques.
Key Results
In 12 of 14 mouse vasa deferentia, slow bath application of epibatidine (100 nM) had no significant effect on excitatory junction potential (EJP) amplitude and spontaneous EJP (SEJP) frequency. However, rapid application of epibatidine to the mouse vas deferens caused an increase in SEJP frequency (by 530%), with no effect on EJP amplitude. Despite the absence of an effect on EJPs, electrically-evoked contractions of the mouse vas deferens were significantly increased in the presence of epibatidine (by 50%). A transient contraction was reliably induced by a higher epibatidine concentration (1 μM). This contraction was significantly reduced in the presence of prazosin, tetrodotoxin, or α,β-methyleneATP. Epibatidine did not induce a contraction in the presence of a combination of prazosin, α,β-methyleneATP and cyclopentolate.
In the guinea pig, bath-applied epibatidine potentiated EJP amplitude in a biphasic pattern, lasting for at least 30 minutes.
Conclusion and Implications
The nAChR-mediated augmentation of neurogenic contraction is indeed prejunctional, but in the mouse arises from an increase in spontaneous neurotransmitter release that primes smooth muscle for subsequent contraction, while in the guinea pig there is a direct augmentation of evoked neurotransmitter (ATP) release.
doi:10.1038/sj.bjp.0707183
PMCID: PMC2013884  PMID: 17325648
Prejunctional; nicotinic; epibatidine; intracellular recording; mouse; guinea pig; vas deferens; sympathetic; electrophysiology; neurotransmission
9.  Anti-histaminic, mast cell stabilizing and bronchodilator effect of hydroalcoholic extract of polyherbal compound– Bharangyadi 
Ancient Science of Life  2012;31(3):95-100.
Bronchial asthma is a chronic inflammatory disorder of the airways associated with reversible airway obstruction and increased airway responsiveness to a variety of stimuli. An intuitive inference from this definition is that a causal relationship may exist between airway inflammation and airway hyperresponsiveness. It can be say that “airway inflammation equal to airway hyperresponsiveness”. Attachment of antigen antibody complex to the mast cell causes its disruption and release of inflammatory mediators such as histamine.To evaluate the efficacy of anti-asthmatic property of a drug, evaluation of anti-histaminic, mast cell stabilizing and bronchodilator property can be use as pharmacodynamic parameter. Bharangyadi is a polyherbal compound having Bharangi (Clerodendrum serratum), Sati (Hedychium spicatum) and Pushkarmoola (Inula racemosa) as ingredient herbs The present study aimed to evaluate the anti-asthmatic activity of an indigenous polyherbal compound Bharangyadi through various in-vitro & in-vivo experimental models.
The results demonstrate that drug has potent histamine antagonism property with significant mast cell stabilizing and spasmolytic activity in the experimental animals. Compound 48/80, a potent mast cell degranulator, provoked 76% degranulation of mast cells in the control group. Ethanolic extract of Bharangyadi at the doses 500 and 1000 μg/ml protected from compound 48/80-evoked degranulation (P < 0.01) in dose dependent manner.
Pre-treatment with Bharangyadi extract showed 80% & 86% protection from histamine induced bronchoconstriction in guinea pigs with 27.8% and 36.1% increase in preconvoulsion time (equal to standard drug). Screening of Histamine antagonism activity on guinea pig ileum showed that drug reduces the smooth muscle contraction in dose dependent manner. Increasing concentration of Bharangyadi extract with maximum dose of histamine (1.6μg) showed maximum inhibition at the dose of 50mg (99.78%). Inhibition of smooth muscle contraction by addition of drug in organ bath before adding histamine showed that drug has preventive type antagonism.
doi:10.4103/0257-7941.103182
PMCID: PMC3530345  PMID: 23284214
Anti-asthmatic; anti-histaminic; Bharangyadi polyherbal compound; bronchodilator; Compound 48/80; mast cell stabilization
10.  The Relaxant Effects of Different Methanolic Fractions of Nigella sativa on Guinea Pig Tracheal Chains 
Objective(s): In regard to the high incidence of asthma and the side-effects of the drugs used, finding novel treatments for this disease is necessary. Our previous studies demonstrated the preventive effect of Nigella sativa extract on ovalbumin-induced asthma. In addition, water-soluble substances of N. sativa extract and methanol fraction of this plant were responsible for the relaxant effect of this plant on tracheal chains of guinea pigs. Therefore, for the first time, in the present study, in order to identify main constituents of the methanolic extract, the relaxant effects of five different methanolic fractions (20%, 40%, 60%, 80%, and 100%) of N. sativa on tracheal chains of guinea pigs were examined.
Materials and Methods: The relaxant effects of four cumulative concentrations of each fraction (0.8, 1.2, 1.6, and 2.0 g%) in comparison with saline as negative control and four cumulative concentrations of theophylline (0.2, 0.4, 0.6, and 0.8 mM) were examined by their relaxant effects on precontracted tracheal chains of guinea pig by 60 mM KCl (group 1) and 10 µM methacholine (group 2).
Results: In group 1, all concentrations of only theophylline showed significant relaxant effects but all concentrations of these methanolic fractions showed significant contractile effects compared with that of saline (P<0.001 to P<0.05). However, in group 2, all concentrations of theophylline and these methanolic fractions showed significant relaxant effects compared with that of saline (P<0.001 to P<0.05).
Conclusion: These results showed a potent relaxant effect of 20% methanolic fractions from N. sativa on tracheal chains of guinea pigs that were higher than that of theophylline at the used concentrations.
PMCID: PMC3843853  PMID: 24298378
Guinea Pig; Methanolic Fractions; Nigella sativa; Relaxant Effect; Tracheal Chain
11.  In Vitro Anticholinergic and Antihistaminic Activities of Acorus Calamus Linn. Leaves Extracts 
The present investigation was aimed at determining the effects of hexane, acetone, methanol and aqueous extracts of Acorus calamus leaves (ACHE, ACAE, ACME and ACAQE) on cholinergic and histaminic system using isolated frog rectus abdominis muscle and guinea pig ileum. A dose dependent potentiation of Ach response (anticholinesterase like effect) was found with ACAE and ACME at 0.25, 0.5, 0.75 and 1 mg/ml, but at higher dose of ACAE, ACME, ACAQE and ACHE (5, 20 mg/ml) inhibit the Ach response (antinicotinic effect). These results revealed biphasic effect of Acorus calamus leaves extracts on acetylcholine induced contractile response in isolated frog rectus abdominis muscle preparation (i.e. potentiation effect at lower dose and inhibitory effect at higher dose). Studies on isolated guinea pig ileum demonstrated antihistaminic effect in a dose dependent manner (100–1000 µg/ml) with ACAE, ACME and ACAQE. In addition, the dose dependent inhibition of Ach response (antimuscarinic effect) was observed with ACAE and ACME. In conclusion, Acorus calamus leaves extracts exerts antinicotinic, anticholinesterase like activities in isolated frog rectus abdominis muscle and antihistaminic, antimuscarinic effect in guinea pig ileum. It has been suggested that these observed activities can be further studied for therapeutic potential of Acorus calamus leaves in the treatment of cognitive disorders and asthma.
PMCID: PMC3746362  PMID: 24082330
Sweet flag leaves; anticholinesterase; antimuscarinic; antinicotinic; cumulative dose response; biphasic effect
12.  An overview of species differences in the effects of a water extract of cotton bract on isolated airway smooth muscle, and effects of E. coli lipopolysaccharide. 
Our laboratory has been comparing the activity of a water extract of cotton bract (CBE) with the isolated trachealis smooth muscle of the dog, guinea pig, and cat. CBE induced contractions that were not mediated by 5-hydroxytryptamine (5-HT), histamine, or muscarinic receptors. The active agent(s) in CBE was dialyzable (less than 14,000 molecular weight), and substantial activity was retained after low-temperature ashing. CBE potentiated contractions of dog trachealis to histamine and 5-HT and relaxation responses to isoproterenol, whereas it had no effect on responses to methacholine and KCl. In the guinea pig trachealis, CBE reduced responsiveness to KCl, potentiated relaxations to adenosine and ATP, and did not alter the responses to the remaining agents. Responses of cat trachealis to KCl and isoproterenol were potentiated by CBE, while those to 5-HT were unaffected. Neurogenic cholinergic contractile responses were potentiated by CBE in the trachealis of the dog, but not of the guinea pig, while neurogenic relaxations were potentiated by CBE in guinea pig trachealis but not in the dog trachealis. There are thus marked species differences in the acute effects of CBE on airway smooth muscle. Due to recent interest in the possible involvement of bacterial endotoxins in the etiology of byssinosis, we examined the effects of E. coli lipopolysaccharide (LPS) in guinea pig trachealis. An initial examination revealed that LPS potentiated responses to histamine, but not those to methacholine and isoproterenol. This effect vanished upon a second appraisal with a different batch of LPS. The effect of LPS in airway smooth muscle is thus, at present, equivocal.
PMCID: PMC1474393  PMID: 3011394
13.  Inhibition of Release of Vasoactive and Inflammatory Mediators in Airway and Vascular Tissues and Macrophages By a Chinese Herbal Medicine Formula for Allergic Rhinitis 
Herbal therapies are being used increasingly for the treatment of allergic rhinitis. The aim of this study was to investigate the possible pharmacological actions and cellular targets of a Chinese herbal formula (RCM-101), which was previously shown to be effective in reducing seasonal allergic rhinitis symptoms in a randomized, placebo-controlled clinical trial. Rat and guinea pig isolated tissues (trachea and aorta) were used to study the effects of RCM-101 on responses to various mediators. Production of leukotriene B4 in porcine neutrophils and of prostaglandin E2 and nitric oxide (NO) in Raw 264.7 cells were also measured. In rat and guinea pig tracheal preparations, RCM-101 inhibited contractile responses to compound 48/80 but not those to histamine (guinea pig preparations) or serotonin (rat preparations). Contractile responses of guinea pig tracheal preparations to carbachol and leukotriene C4, and relaxant responses to substance P and prostaglandin E2 were not affected by RCM-101. In rat aortic preparations, precontracted with phenylephrine, endothelium-dependent relaxant responses to acetylcholine and endothelium-independent relaxant responses to sodium nitroprusside were not affected by RCM-101. However, RCM-101 inhibited relaxations to l-arginine in endothelium-denuded rat aortic preparations, which had been pre-incubated with lipopolysaccharide. RCM-101 did not affect leukotriene B4 formation in isolated porcine neutrophils, induced by the calcium ionophore A23187; however, it inhibited prostaglandin E2 and NO production in lipopolysaccharide-stimulated murine macrophages (Raw 264.7 cells).The findings indicate that RCM-101 may have multiple inhibitory actions on the release and/or synthesis of inflammatory mediators involved in allergic rhinitis.
doi:10.1093/ecam/nel083
PMCID: PMC1876611  PMID: 17549238
allergic rhinitis; Chinese herbal medicine; histamine; inducible nitric oxide synthase; inflammation; leukotriene B4; prostaglandin E2; seasonal allergic rhinitis formula (RCM-101)
14.  PRELIMINARY GASTROINTESTINAL STUDIES OF METHANOL EXTRACT OF INDIGOFERA PULCHRA WILLD IN RODENTS 
In this study, the effect of the methanol extract of Indigofera pulchra Willd. (Papillionaceae) was investigated against castor oil induced diarrheoa. Its effects on perfused isolated rabbit jejunum and guinea pig ileum were also evaluated. The extract produced a dose-dependent protection against the castor oil-induced diarrheoa in mice with the highest protection (100%), obtained at 200 mgkg−1 comparable to that of loperamide (5 mgkg−1), a standard antidiarrhoeal drug. The extract (0.4 – 6.4 mgml−1) produced a concentration relaxation of the rabbit jejunum. However, no observable effect was noticed when the guinea pig ileum was treated. The extract blocked the contractile effect of acetylcholine (2 × 10−8 gml−1) and histamine (4 × 10−7 gml−1) on both rabbit jejunum and guinea pig ileum. Phytochemical screening revealed the presence of flavonoids, tannins, saponins and steroids. The intraperitoneal median lethal dose (LD50) value for the extract was found to be 2154.0 mgkg−1. The results obtained revealed that the extract possesses pharmacologically active compounds with gastrointestinal relaxant and antidiarrhoeal activities and may possibly explain the use of the plant in traditional medicine for the treatment of gastrointestinal disorder.
PMCID: PMC3011224  PMID: 21197141
Indigofera pulchra; jejunum; ileum; diarrhoea; medicinal plants
15.  Forskolin Changes the Relationship between Cytosolic Ca2+ and Contraction in Guinea Pig Ileum 
This study was designed to clarify the mechanism of the inhibitory effect of forskolin on contraction, cytosolic Ca2+ level ([Ca2+]i), and Ca2+ sensitivity in guinea pig ileum. Forskolin (0.1 nM~10 µM) inhibited high K+ (25 mM and 40 mM)- or histamine (3 µM)-evoked contractions in a concentration-dependent manner. Histamine-evoked contractions were more sensitive to forskolin than high K+-evoked contractions. Spontaneous changes in [Ca2+]i and contractions were inhibited by forskolin (1 µM) without changing the resting [Ca2+]i. Forskoln (10 µM) inhibited muscle tension more strongly than [Ca2+]i stimulated by high K+, and thus shifted the [Ca2+]i-tension relationship to the lower-right. In histamine-stimulated contractions, forskolin (1 µM) inhibited both [Ca2+]i and muscle tension without changing the [Ca2+]i-tension relationship. In α-toxin-permeabilized tissues, forskolin (10 µM) inhibited the 0.3 µM Ca2+-evoked contractions in the presence of 0.1 mM GTP, but showed no effect on the Ca2+-tension relationship. We conclude that forskolin inhibits smooth muscle contractions by the following two mechanisms: a decrease in Ca2+ sensitivity of contractile elements in high K+-stimulated muscle and a decrease in [Ca2+]i in histamine-stimulated muscle.
doi:10.4196/kjpp.2009.13.3.189
PMCID: PMC2766733  PMID: 19885036
Fosrkolin; Cytosolic Ca2+; Ca2+ sensitivity; Guinea pig ileum
16.  Propofol Preferentially Relaxes Neurokinin Receptor 2-induced Airway Smooth Muscle Contraction in Guinea Pig Trachea 
Anesthesiology  2010;112(6):1335-1344.
Background
Propofol is the anesthetic of choice for patients with reactive airway disease and is thought to reduce intubation- or irritant-induced bronchoconstriction by decreasing the cholinergic component of vagal nerve activation. However, additional neurotransmitters including neurokinins play a role in irritant-induced bronchoconstriction. We questioned the mechanistic assumption that propofol's clinically recognized protective effect against irritant-induced bronchoconstriction during intubation was due to attenuation of airway cholinergic reflexes.
Methods
Muscle force was continuously recorded from isolated Guinea pig tracheal rings in organ baths. Rings were subjected to exogenous contractile agonists (acetylcholine, histamine, endothelin-1, substance P, acetyl-substance P and neurokinin A) or to electrical field stimulation (EFS) to differentiate cholinergic or non-adrenergic, non-cholinergic nerve mediated contraction with or without cumulatively increasing concentrations of propofol, thiopental, etomidate or ketamine.
Results
Propofol did not attenuate the cholinergic component of EFS-induced contraction at clinically relevant concentrations. In contrast, propofol relaxed non-adrenergic, non-cholinergic mediated EFS contraction at concentrations within the clinical range ((20-100 μM) n = 9, P < 0.05) and propofol was more potent against an exogenous selective neurokinin 2 receptor versus neurokinin 1 receptor agonist contraction (n = 6, p < 0.001).
Conclusions
Propofol, at clinically relevant concentrations, relaxes airway smooth muscle contracted by nonadrenergic, noncholinergic-mediated EFS and exogenous neurokinins but not contractions elicited by the cholinergic component of EFS. These findings suggest that the mechanism of propofol's protective effects against irritant-induced bronchoconstriction involves attenuation of tachykinins released from nonadrenergic, noncholinergic nerves acting at neurokinin 2 receptors on airway smooth muscle.
doi:10.1097/ALN.0b013e3181d3d7f6
PMCID: PMC3655426  PMID: 20461005
17.  Effect of aqueous fraction of Rosa damascena on ileum contractile response of guinea pigs 
Objective: The use of drugs with herbal origin is increasing for treatment of gastrointestinal (GI) disorders. Rosa damascena (R. damascena) is a well-known plant suggested to have beneficial effect on GI system. In this study, the effect of aqueous fraction of R. damascena on the contractions of isolated guinea pig ileum was investigated.
Materials and Methods: Aqueous fraction of plant was obtained from ethanolic extract after ethyl acetate and n-butanol fractions were discarded. To evaluate effect of this fraction on ileum contraction, guinea pig ileum was removed and mounted on organ bath and its contraction was recorded. Effect of various concentrations (0.66, 0.83, and 1.3 mg/ml) of aqueous fraction on ileum contraction in comparison with Ach in presence and absence of atropine, a muscarinic antagonist of cholinergic, was evaluated. The response of ileum to 1 µg/ml of acetylcholine was considered as 100% response.
Results: Our results showed that aqueous fractions of R. damascena dose-dependently increased basal guinea pigs ileum contractions (p<0.05 to p<0.001). Maximal contraction of fraction (1.3 mg/ml) induced 23.4 % of maximal Ach response. The contraction of ileum to aqueous fraction was significant decreased in presence 0.001 µg/ml of atropine.
Conclusion: It is concluded that aqueous fraction of R. damascena has mild excitatory effect on ileum contraction and this fraction may be beneficial as a mild laxative agent.
PMCID: PMC4075714  PMID: 25050281
Aqueous Fraction; Cholinergic System; Guinea Pig; Ileum; Rosa damascena
18.  Inhibitory effects of genistein and resveratrol on guinea pig gallbladder contractility in vitro 
AIM: To observe and compare the effects of phytoestrogen genistein, resveratrol and 17β-estradiol on the tonic contraction and the phasic contraction of isolated gallbladder muscle strips and to study the underlying mechanisms.
METHODS: Isolated strips of gallbladder muscle from guinea pigs were suspended in organ baths containing Kreb’s solution, and the contractilities of strips were measured before and after incubation with genistein, resveratrol and 17β-estradiol respectively.
RESULTS: Similar to 17β-estradiol, genistein and resveratrol could dose-dependently inhibit the phasic contractile activities, they decreased the mean contractile amplitude and the contractile frequencies of gallbladder muscle strips, and also produced a marked reduction in resting tone. The blocker of estrogen receptor ICI 182780 failed to alter the inhibitory effects induced by genistein and resveratrol, but potassium bisperoxo (1, 10 phenanthroline) oxovanadate bpV (phen), a potent protein tyrosine phosphatase inhibitor, markedly attenuated the inhibitory effects induced by genistein and resveratrol. In calcium-free Kreb’s solution containing 0.01 mmol/L egtazic acid (EGTA), genistein and resveratrol inhibited the first phasic contraction induced by acetylcholine (ACh), but did not affect the second contraction induced by CaCl2. In addition, genistein, resveratrol and 17β-estradiol also could reduce the contractile responses of ACh and KCl, and shift their cumulative concentration-response curves rightward.
CONCLUSION: Phytoestrogen genistein and resveratrol can directly inhibit the contractile activity of isolated gallbladder muscle both at rest and in response to stimulation. The mechanisms responsible for the inhibitory effects probably due mainly to inhibition of tyrosine kinase, Ca2+ influx through potential-dependent calcium channels (PDCs) and Ca2+ release from sarcoplasmic reticulum (SR), but were not related to the estrogen receptors.
doi:10.3748/wjg.14.4955
PMCID: PMC2739951  PMID: 18756606
Phytoestrogen; Estradiol; Gallbladder; Smooth muscle; Ca2+ channel
19.  Pharmacological Effects of Lactuca serriola L. 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.
doi:10.1155/2013/304394
PMCID: PMC3638630  PMID: 23662127
20.  Receptor-specific mediation by immunoglobulin E of antigen-induced contraction of tracheal and lung parenchymal strips isolated from the guinea pig. 
Journal of Clinical Investigation  1984;73(4):1215-1222.
The guinea pig is much like humans in the cells and mediators involved in immediate hypersensitivity reactions. However, the major anaphylactic antibody in this species is IgG1, not IgE. Recently, we have been successful in producing IgE antibody in guinea pigs. The current study examined whether guinea pig IgE antibody could mediate pulmonary smooth muscle contraction. IgE antibody to picryl and oxazolone determinants was induced by immunizing Hartley strain guinea pigs pretreated with cyclophosphamide. Hyperimmune serum from these animals was passed through a heavy chain-specific anti-IgG1 affinity column. The presence of IgE anti-hapten antibody in the filtrate fraction was verified by passive cutaneous anaphylaxis (PCA) testing with a 7-d period of local passive sensitization and by heat lability (56 degrees C X 4 h) of PCA activity. This IgE-rich fraction, and purified IgG1 anti-hapten antibody were transferred to normal guinea pigs. Both fractions sensitized trachea and pulmonary parenchyma for antigen-induced smooth muscle contraction. The IgG1-mediated antigen-induced contractile response was not affected by heat (56 degrees C X 4 h) and was inhibited in a dose-dependent fashion by IgG1 blocking antibody (anti-OA). The IgE-mediated antigen-induced contractile response was significantly decreased by heat and was not affected by the anti-OA blocking antibody even at a concentration of 100 mg/kg. Thus, two antigen-specific factors in guinea pig serum can mediate antigen-induced pulmonary smooth muscle contraction: IgG1 and IgE antibodies. Our data also suggests that these antibodies mediate the contractile response through separate receptors. The finding that guinea pig IgE can mediate pulmonary smooth muscle contraction suggests this species can be a model for IgE-mediated events in the lung.
PMCID: PMC425135  PMID: 6231313
21.  Effects of fire and fire intensity on the germination and establishment of Acacia karroo, Acacia nilotica, Acacia luederitzii and Dichrostachys cinerea in the field 
BMC Ecology  2004;4:3.
Background
While fire has been used in some instances to control the increase of woody plants, it has also been reported that fire may cause an increase in certain fire-tolerant Acacia tree species. This study investigated germination of Acacia karroo, A. luederitzii and Dichrostachys cinerea, thought to be increasing in density, as well as the historically successful encroaching woody species, A. nilotica, in savanna grassland, Hluhluwe-iMfolozi Park, South Africa. A. karroo is thought to be replacing A. nilotica as the dominant microphyllous species in the park. We tested the hypothesis that observed increases in certain woody plants in a savanna were related to seed germination and seedling establishment. Germination is compared among species for burnt and unburnt seeds on burnt and unburnt plots at three different locations for both hot and cool fires.
Results
Acacia karroo showed higher germination (A. karroo 5.1%, A. nilotica 1.5% and A. luederitzii 5.0%) levels and better establishment (A. karroo 4.9%, A. nilotica 0.4% and A. luederitzii 0.4%). Seeds of the shrub Dichrostachys cinerea did not germinate in the field after fire and it is thought that some other germination cue is needed. On average, burning of A. karroo, A. nilotica and A. luederitzii seeds did not affect germination. There was a significant difference in the germination of burnt seeds on burnt sites (4.5%) and burnt seeds on unburnt plots (2.5%). Similarly, unburnt seeds on unburnt sites germinated better (4.9%) than unburnt seeds on burnt sites (2.8%).
Conclusion
We conclude that a combination of factors may be responsible for the success of A. karroo and that fires may not be hot enough or may occur at the wrong time of year to control A. karroo establishment in HiP. Although germination and establishment of A. karroo was higher than for A. nilotica a competitive advantage after fire could not be shown.
doi:10.1186/1472-6785-4-3
PMCID: PMC406512  PMID: 15068486
22.  Parainfluenza 3 Infection Blocks the Ability of a Beta Adrenergic Receptor Agonist to Inhibit Antigen-induced Contraction of Guinea Pig Isolated Airway Smooth Muscle 
Journal of Clinical Investigation  1981;67(2):376-384.
Guinea pigs, actively sensitized to ovalbumin, were inoculated by nasal insufflation with parainfluenza 3 or virus growth medium 4 d before performing in vitro pharmacological studies on tracheal and bronchial smooth muscle. In each airway segment, cumulative dose-response effects of ovalbumin were obtained in the absence and presence of a maximally effective concentration of a beta adrenergic receptor agonist, sulfonterol. Sulfonterol shifted the dose-response curve to the right and reduced the maximum smooth muscle contractile response to ovalbumin. Virus infection did not alter the dose-response effects of ovalbumin. However, the magnitude of the inhibitory effects of sulfonterol was smaller in segments taken from animals inoculated with virus. Blockade by virus infection of the inhibitory effect of sulfonterol was reversed when the concentrations of beta agonist were increased. Sulfonterol did not alter the dose-response effects of histamine at any of the concentrations that markedly antagonized the effects of ovalbumin. Virus infection did not alter the sensitivities to sulfonterol or papaverine in producing relaxation in either airway segment. The magnitude of relaxation produced by papaverine was significantly larger in bronchial rings taken from animals infected with virus for 4 d, but there was no alteration by virus of the dose-response effects of histamine or carbachol. In experiments measuring antigen-induced release of slow reacting substance of anaphylaxis and histamine from minced lung, virus infection did not alter the sensitivity or the maximum effects of ovalbumin. Also, the ability of sulfonterol to inhibit the release of slow reacting substance of anaphylaxis and histamine was not affected by virus infection.
These results demonstrate that infection of guinea pigs with respiratory virus results in a selective blockade of the beta adrenergic-mediated inhibition of antigen-induced contraction of airway smooth muscle. The guinea pig may serve as a useful model in physiological studies of virus-induced asthma.
PMCID: PMC370578  PMID: 6109736
23.  Modulation of cholinergic neural bronchoconstriction by endogenous nitric oxide and vasoactive intestinal peptide in human airways in vitro. 
Journal of Clinical Investigation  1993;92(2):736-742.
Human airway smooth muscle possesses an inhibitory nonadrenergic noncholinergic neural bronchodilator response mediated by nitric oxide (NO). In guinea pig trachea both endogenous NO and vasoactive intestinal peptide (VIP) modulate cholinergic neural contractile responses. To identify whether endogenous NO or VIP can modulate cholinergic contractile responses in human airways in vitro, we studied the effects of specific NO synthase inhibitors and the peptidase alpha-chymotrypsin on contractile responses evoked by electrical field stimulation (EFS) at three airway levels. Endogenous NO, but not VIP, was shown to inhibit cholinergic contractile responses at all airway levels but this inhibition was predominantly in trachea and main bronchus and less marked in segmental and subsegmental bronchi. To elucidate the mechanism of this modulation we then studied the effects of endogenous NO on acetylcholine (ACh) release evoked by EFS from tracheal smooth muscle strips. We confirmed that release was neural in origin, frequency dependent, and that endogenous NO did not affect ACh release. These findings show that endogenous NO, but not VIP, evoked by EFS can inhibit cholinergic neural responses via functional antagonism of ACh at the airway smooth muscle and that the contribution of this modulation is less marked in lower airways.
PMCID: PMC294908  PMID: 8349813
24.  Evaluation of Antiasthmatic Activity of Curculigo orchioides Gaertn. Rhizomes 
The ethanol extract of Curculigo orchioides was evaluated for antiasthmatic activity by using various in vitro and in vivo animal models. In vitro models like isolated goat tracheal chain preparation and isolated guinea pig ileum preparation were studied to know basic mechanism by which extract shows relaxant activity. The study showed that extract is effective against histamine-induced contraction. In isolated goat tracheal chain preparation and isolated guinea pig ileum preparation extract exhibits maximum relaxant effect (p< 0.01) against histamine at concentrations 100μg/ml and 25μg/ml respectively. Animal studies involved use of histamine induced bronchoconstriction in guinea pigs, egg albumin induced passive paw anaphylaxis in rats and haloperidol-induced catalepsy in mice. These studies showed significant (p< 0.01) protection at lower doses while further increase in the dose level showed reduced activity. Biochemical estimations in milk-induced total leukocytes count and milk-induced differential leukocyte count were also studied. In this study there was maximum increase in leucocytes and lymphocytes (99%) and maximum decrease in eosinophils up to 0% at dose 375mg/kg p.o. body weight was observed. The results of these studies indicated usefulness of ethanol extract of Curculigo orchioides in asthma.
doi:10.4103/0250-474X.44590
PMCID: PMC2792544  PMID: 20046767
Antiasthmatics; bronchoconstriction; Curculigo orchioides; eosinophils
25.  Butylidenephthalide Blocks Potassium Channels and Enhances Basal Tension in Isolated Guinea-Pig Trachea 
BioMed Research International  2014;2014:875230.
Butylidenephthalide (Bdph, 30~300 μM), a constituent of Ligusticum chuanxiong Hort., significantly enhanced tension in isolated guinea-pig trachea. In this study, we investigate the mechanism(s) of Bdph-induced contraction in the tissue. Isolated trachea was bathed in 5 mL of Krebs solution containing indomethacin (3 μM), and its tension changes were isometrically recorded. Cromakalim (3 μM), an ATP-dependent K+ channel opener, significantly antagonized the Bdph-induced enhancement of baseline tension. Bdph (300 μM) also significantly antagonized cromakalim-induced relaxation. Bdph (300 μM) did not significantly influence the antagonistic effects of glibenclamide (GBC, 1 μM) and tetraethylammonium (TEA, 8 mM) against the cromakalim-induced relaxation. However, Bdph (300 μM) and 4-aminopiridine (4-AP, 5 mM), a blocker of Kv1 family of K+ channels, in combination significantly rightward shifted the log concentration-relaxation curve of cromakalim. The antagonistic effect of the combination almost equals the sum of the individual effects of Bdph and 4-AP, suggesting that the antagonistic mechanism of Bdph may be similar to that of 4-AP. All calcium channel blockers influenced neither the baseline tension nor antagonistic effect of Bdph against cromakalim. In conclusion, Bdph may be similar to 4-AP, a blocker of Kv1 family of K+ channels, to enhance the baseline tension of guinea-pig trachea.
doi:10.1155/2014/875230
PMCID: PMC4119919  PMID: 25114927

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