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1.  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
2.  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
3.  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)
4.  Studies on tracheorelaxant and anti-inflammatory activities of rhizomes of Polygonatum verticillatum 
Background
The present study describes the tracheorelaxant and anti-inflammatory effects of Polygonatum verticillatum which may support its medicinal use in hyperactive airway complaints and inflammatory disorders.
Methods
The tracheorelaxant activity of crude extract of the rhizomes of P. verticillatum (PR) was assessed in isolated guinea-pig tracheal tissues immersed in tissue organ bath filled with Tyrode’s solution and a continuous supply of carbogen gas (95% O2 and 5% CO2). The contractile and relaxant responses of the tissue were measured using isometric transducers coupled with Power-Lab data acquisition system. The anti-inflammatory effect was evaluated in carrageenan-induced rat paw edema model, while the lipoxygenase inhibitory activity was performed in the in-vitro assay. Various chromatographic and spectroscopic techniques were used for the isolation and characterization of pure molecules.
Results
In isolated guinea-pig tracheal preparations, PR caused complete inhibition of the high K+ (80 mM) and carbachol-induced contractions however, it was more potent against K+ than CCh, similar to verapamil. Pretreatment of the tissue with PR, displaced the Ca2+ concentration-response curves to the right, similar to that induced by verapamil, indicating the presence of Ca2+ channel blocking like activity. When tested on carrageenan-induced rat paw edema, PR demonstrated a marked reduction in edema with 65.22% protection at 200 mg/kg, similar to aspirin. In the in-vitro assay, PR showed lipoxygenase inhibitory activity (IC50: 102 ± 0.19 μg/mL), similar to baicalein. Bioactivity-guided fractionation led to the isolation of 2-hydroxybenzoic acid and β-sitosterol.
Conclusions
These results indicate that the plant possesses tracheorelaxant, mediated possibly through a Ca2+ channel blockade mechanism, and anti-inflammatory activities, which may explain the medicinal use of this plant in airway disorders and inflammation.
doi:10.1186/1472-6882-13-197
PMCID: PMC3772698  PMID: 23895558
Polygonatum verticillatum; Bronchodilator; Ca2+ antagonist; Anti-inflammatory; 2- Hydroxybenzoic acid; β-sitosterol
5.  The Pharmacological Activity of Extracts of Cotton Dust 
Aqueous extracts prepared from dust collected in the card-rooms of several cotton mills have been prepared and found to contain activity which contracts the smooth muscle of guinea-pig ileum, guinea-pig trachea, rat stomach strip, and rat duodenum. The extracts contained an unknown contractor substance which was dialysable, resistant to boiling for one hour, and not destroyed by the action of proteolytic enzymes. They also contained a small amount of 5-hydroxytryptamine. One of the dust samples also contained histamine, but it could not be detected in the other samples, one of which was known to possess bronchoconstrictor properties in man. The particulate material, even after repeated washing, was found to have some stimulant action on guinea-pig ileum.
There was no evidence for the release of histamine by the extracts in either cats or guinea-pigs, although a very small amount was released in rats. Jute dust is much less active than cotton dust, and the activity differs qualitatively. Cotton dust extracts were found to have pyrogenic activity but it is unlikely that pyrogens were responsible for the smooth-muscle contractor properties. Experiments with whole animals suggest that although smooth-muscle contracting substances were present in the extracts, it is possible that the symptoms of byssinosis are caused by the release of some other active bronchoconstrictor substance in the tissues. The mechanism of the release is not known; it may be caused by a soluble principle in the extract or due to the presence of particulate matter in the dust.
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PMCID: PMC1038127  PMID: 13883719
6.  TOXIC SUBSTANCES PRODUCED BY PNEUMOCOCCUS 
1. The filtered blood serum of rabbits infected with pneumococci is not toxic. 2. Extracts of pneumococci prepared by keeping emulsions of the bacteria in salt solution at 37° C. for varying periods of time may be toxic, and when injected intravenously into guinea pigs, may produce a train of symptoms followed by acute death resembling that seen in acute anaphylaxis. Such extracts, however, are not uniformly toxic and it has been impossible to discover the exact conditions under which such extracts become toxic. 3. When the centrifugalized peritoneal washings of guinea pigs infected with pneumococci are injected into the circulation of normal guinea pigs, these animals very frequently exhibit symptoms like those seen in acute anaphylaxis, and a considerable proportion of the animals die acutely. 4. When pneumococci are dissolved in dilute solutions of bile salts and the solution resulting is injected intravenously into rabbits and guinea pigs, these animals show with great constancy the same symptoms that are seen in acute anaphylaxis. The solution of pneumococci in bile may occur in ten minutes at 37° C. or in half an hour on ice. This is considered evidence that the toxicity of the solution does not result from digestion of the bacterial protein, but is due to substances preformed in the bacterial cells and set free on their solution. The toxicity of the solution is diminished or destroyed by heating to 55° C. or over.
PMCID: PMC2124997  PMID: 19867603
7.  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
8.  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
9.  Species and tissue-specificity of prokinetic, laxative and spasmodic effects of Fumaria parviflora 
Background
Fumaria parviflora Linn. (Fumariaceae), is a small branched annual herb found in many parts of the world including Saudi Arabia and Pakistan. This study was designed to provide pharmacological basis for the medicinal use of Fumaria parviflora in gut motility disorders.
Methods
The in-vivo prokinetic and laxative assays were conducted in mice. Isolated intestinal preparations (ileum and jejunum) from different animal species (mouse, guinea-pig and rabbit) were separately suspended in tissue baths containing Tyrode's solution bubbled with carbogen and maintained at 37°C. The spasmogenic responses were recorded using isotonic transducers coupled with PowerLab data acquisition system.
Results
The aqueous-methanol extract of Fumaria parviflora (Fp.Cr), which tested positive for the presence of alkaloids, saponins, tannins and anthraquinones showed partially atropine-sensitive prokinetic and laxative activities in the in-vivo in mice at 30 and 100 mg/kg. In the in-vitro studies, Fp.Cr (0.01-1 mg/ml) caused a concentration-dependent atropine-sensitive stimulatory effect both in mouse tissues (jejunum and ileum), and rabbit jejunum but had no effect in rabbit ileum. In guinea-pig tissues (ileum and jejunum), the crude extract showed a concentration-dependent stimulatory effect with higher efficacy in ileum and the effect was partially blocked by atropine, indicating the involvement of more than one types of gut-stimulant components (atropine-sensitive and insensitive). This could be a plausible reason for the greater efficacy of Fp.Cr in gut preparations of guinea-pig than in rabbit or mouse.
Conclusions
This study shows the prokinetic, laxative and spasmodic effects of the plant extract partially mediated through cholinergic pathways with species and tissue-selectivity, and provides a sound rationale for the medicinal use of Fumaria parviflora in gut motility disorders such as, indigestion and constipation. This study also suggests using different species to know better picture of pharmacological profile of the test material.
doi:10.1186/1472-6882-12-16
PMCID: PMC3324389  PMID: 22405321
10.  Calcium antagonistic activity of Bacopa monniera in guinea-pig trachea 
Indian Journal of Pharmacology  2012;44(4):516-518.
Objective:
To demonstrate the calcium antagonistic property of ethanol extract of Bacopa monniera in guinea-pig trachea.
Materials and Methods:
The dose response curves of CaCl2 (1 × 10-5 to 1 × 10-1 M) were constructed in the absence and presence of ethanol extract of Bacopa monniera (100, 500 and 700 μg/ml) or nifedipine (1 × 10-6 M) in guinea-pig trachea in calcium free high K+-MOPS-PSS (3-(N-morpholino)-propanesulphonic acid physiological salt solution). The data was analyzed by ANOVA followed by least significant difference test or by Student's ‘t’ test for unequal variance when appropriate. A probability of at least P < 0.05 was considered statistically significant.
Results:
The plant extract (500 and 700 μg/ml) significantly (P < 0.05) depressed and shifted the calcium concentration-response curves (1 × 10-3- 1 × 10-1 M) to rightward similar to that of nifedipine.
Conclusions:
Bacopa monniera extract exhibited calcium channel blocking activity in guinea-pig tracheal smooth muscles that may rationalize its relaxant action on guinea-pig trachea and its traditional use in respiratory disorders.
doi:10.4103/0253-7613.99336
PMCID: PMC3469959  PMID: 23087517
Bacopa monniera; calcium channel antagonist; smooth muscle relaxation
11.  Prokinetic and laxative effects of the crude methanolic extract of Viola betonicifolia whole plant in rodents 
Background
The present study was aimed to provide ethnopharmacological basis for the medicinal use of Viola betonicifolia whole plant in indigestion and constipation.
Methods
Mice were used in in-vivo prokinetic and laxative studies while in-vitro experiments were conducted on isolated tissues of rabbit and guinea-pig gut preparations suspended in a tissue bath to measure isotonic contractions.
Results
The crude methanolic extract of Viola betonicifolia (VBME) showed partially atropine-sensitive prokinetic (50 and 100 mg/kg) and laxative (30 and 100 mg/kg) activities in mice. When tested in isolated rabbit jejunum and guinea-pig ileum, VBME caused dose-dependent contractions at 0.01-0.3 mg/mL and 0.03-5 mg/mL, respectively. The spasmogenic effect was partially sensitive to atropine, while the presence of pyrilamine, SB203186 or hexamethonium had no effect in both gut preparations. VBME partially inhibited acetylcholinesterase enzyme (19%) in the in-vitro assay. The spasmodic effect of VBME was more efficacious in guinea-pig ileum than rabbit jejunum preparation. The phytochemical analysis of the crude methanolic extract for total alkaloids and saponins revealed that the VBME is a rich source of alkaloids and saponins.
Conclusions
This study showed the prokinetic and laxative effects of Viola betonicifolia in mice, partially mediated through cholinergic action. The in-vitro spasmodic effect of the plant extract was also partially sensitive to atropine indicating more than one mechanisms in the gut stimulant effect. This study provides a rationale for the medicinal use of Viola betonicifolia in indigestion and constipation.
doi:10.1186/1472-6882-13-70
PMCID: PMC3626539  PMID: 23530615
Viola betonicifolia; Prokinetic; Laxative; Cholinergic; Jejunum; Ileum
12.  Anti-Inflammatory Activity of Crude Saponin Extracts from Five Nigerian Medicinal Plants 
Abstact
Crude saponin extracts of five medicinal plants used in the treatment of inflammatory diseases like rheumatoid arthritis, gout and haemorrhoids were screened for anti-inflammatory activity using carrageenan-induced rat paw oedema test. These plants were the whole plant of Schwenkia americana Linn (WSA), the rhizomes of Asparagus africanus Lam (RAA), the leaves of Dichrostachys cinerea Linn (LDC), the stem bark of Ficus iteophylla Miq (BFI) and the leaves of Indigofera pulchra Willd (LIP). A modify traditional method of crude saponins extraction was used to give the following percentage yields: WSA-2.74%, RAA-3.59%, LDC-1.62%, BFI-0.81% and LIP-1.57% respectively. Thin-layer chromatography was used to identify the type of saponins present in the extracts. The acute toxicity study of the crude saponin extracts in mice gave the following intraperitoneal LD50: WSA-471.2mg/kg, RAA- 1264.9mg/kg, LDC-1264.9mg/kg, BFI-118.3mg/kg and LIP-1264.9mg/kg respectively. The anti-inflammatory study of the extracts showed statistically significant (P<0.05) decreases in the rat paw-oedema as compared to the control. The percentage inhibitions of the extracts after four hours were as follow: WSA-61%, RAA-55%, LDC-72%, BFI-66% and LIP-40% respectively. These values were found to be comparable to that of ketoprofen-63%. The study showed that the anti-inflammatory properties attributable to these plants may be due to their saponins contents.
PMCID: PMC3746630  PMID: 23983342
Asparagus africanus; Dichrostachys cinerea; Ficus iteophylla; Indigofera pulchra; Schwenkia americana; Saponin; Anti-inflammatory activity; Carrageenan; TLC
13.  Spasmogenic effect of the Aqueous Extract of Tamarindus Indica L. (Caesalpiniaceae) on the Contractile Activity of Guinea-Pig Taenia Coli 
The effect of aqueous extract of Tamarindus indica (AETI) was studied on the guinea pig taenia coli, due to its use for treatment of constipation in traditional medicines. AETI, at concentrations ranging from 10−8 mg/ml to 10−2 mg/ml, increased the spontaneous contractile activity of guinea pig taenia coli in a dose-dependent manner (EC50= 4×10−6 mg/ml). This activity was unaffected by atropine. In high K+, Ca2+-free solution containing EDTA, AETI as well as acetylcholine, used as a control, induced tonic contraction. These results suggest that the plant extract exert a spasmogenic effect that would not involve cholinergic mechanism of action. However, these active principles could mobilize both extra cellular calcium and intracellular calcium from internal stores.
PMCID: PMC2816490  PMID: 20161887
Contractions; Smooth muscle; Taenia coli; Tamarindus indica
14.  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
15.  Toll-like receptor 7 agonists are potent and rapid bronchodilators in guinea pigs 
Background
Respiratory tract viral infections result in asthma exacerbations. Toll-like receptor (TLR) 7 is a receptor for viral single-stranded RNA and is expressed at high levels in the lungs.
Objective
Because TLR7 polymorphisms are associated with asthma, we examined the effects of TLR7 agonists in guinea pig airways.
Methods
We induced bronchoconstriction in guinea pigs in vivo by means of electrical stimulation of the vagus nerve or intravenous administration of acetylcholine and measured the effect of a TLR7 agonist administered intravenously. We induced contraction of airway smooth muscle in segments of isolated guinea pig tracheas in vitro and measured the effect of TLR7 agonists, antagonists, and pharmacologic inhibitors of associated signaling pathways administered directly to the bath.
Results
TLR7 agonists acutely inhibited bronchoconstriction in vivo and relaxed contraction of airway smooth muscle in vitro within minutes of administration. Airway relaxation induced by the TLR7 agonist R837 (imiquimod) was partially blocked with a TLR7 antagonist and was also blocked by inhibitors of large-conductance, calcium-activated potassium channels; prostaglandin synthesis; and nitric oxide generation. Another TLR7 agonist, 21-mer single-stranded phosphorothioated polyuridylic acid (PolyUs), mediated relaxation that was completely blocked by a TLR7 antagonist.
Conclusions
These data demonstrate a novel protective mechanism to limit bronchoconstriction and maintain airflow during respiratory tract viral infections. The fast time frame is inconsistent with canonical TLR7 signaling. R837 mediates bronchodilation by means of TLR7-dependent and TLR7-independent mechanisms, whereas PolyUs does so through only the TLR7-dependent mechanism. TLR7-independent mechanisms involve prostaglandins and large-conductance, calcium-activated potassium channels, whereas TLR7-dependent mechanisms involve nitric oxide. TLR7 is an attractive therapeutic target for its ability to reverse bronchoconstriction within minutes.
doi:10.1016/j.jaci.2010.10.029
PMCID: PMC3066064  PMID: 21167577
Toll-like receptor 7; asthma; virus; bronchodilator; large-conductance; calcium-activated potassium channel; prostaglandins; adenosine; nitric oxide; imiquimod; IRS661; guinea pig
16.  STUDIES ON THE FORMATION OF COLLAGEN  
Precipitation (or gelation) of collagen from cold neutral salt solution induced by warming was shown to be reversible on subsequent cooling. The degree of reversibility of heat precipitation rapidly diminished with time of incubation at 37°C. For calf skin collagen (acetic acid-extracted) and guinea pig skin collagen (crude NaCl extract) in neutral salt solutions (Γ/2 = 0.45) roughly 90 per cent of newly formed gel redissolved on cooling at 2°C.; less than 20 per cent redissolved on cooling gels previously maintained at 37°C. for 24 hours. At physiologic ionic strength the same preparations exhibited much more rapid development of irreversible precipitation, but the same time dependence was clearly evident. Highly purified collagen from crude saline extracts of guinea pig skin exhibited the same phenomenon although the quantitative aspects were somewhat different.
PMCID: PMC2136865  PMID: 13563757
17.  Possible mechanism of inotropic and chronotropic effects of Rosa damascena on isolated guinea pig heart 
Background
The possible mechanism(s) of inotropic and chronotropic effects of the extract from Rosa damascena (R. damascena) on heart was examined.
Methods
Inotropic and chronotropic effects of four concentrations of the extract from R. damascena and isoprenaline were examined in isolated guinea-pig hearts perfused through aorta in a Langendorff model. All measurements were performed in three different groups: 1) In the presence and absence of propranolol, 2) In the presence and absence of methacholine and 3) In the presence of diltiazem (n = 12 for each group).
Results
In all groups both isoprenaline and the extract caused an increase in heart rate and contractility (p < 0.05 to p < 0.001). Only in group 1, the final concentration of isoprenaline in the absence of propranolol caused significant greater increase in heart rate compared to the extract (207.6 ± 11.0 compared to 162.6 ± 11.8, p < 0.01). The percent increase in heart contractility due to the final concentration of the extract in the absence (362.4 ± 36.9 compared to 227.7 ± 31.6, p < 0.01) and presence of propranolol (577.1 ± 62.9 compared to 357.5 ± 45.6, p < 0.001) in group 1 and absence (403.7 ± 42.1 compared to 244.8 ± 18.9, p < 0.005) and presence of methcholine (499.88 ± 64.64 compared to 323.90 ± 44.49, p < 0.05) in groups 2 was significantly greater than the increase caused by isoprenaline.
Conclusions
The results of this study suggest that inotropic and chornotropic effect of R. damascena is possibly due to the stimulatory effect of this plant on beta-adrenoceptors.
doi:10.1186/2008-2231-21-38
PMCID: PMC3661371  PMID: 23688388
Rosa damascena; Inotropic effect; Chornotropic effect; β-adrenoceptor; Isolated heart
18.  Synthesis of Factor VIII Antigen by Cultured Guinea Pig Megakaryocytes 
Journal of Clinical Investigation  1977;60(4):914-921.
Immunoprecipitates containing guinea pig Factor VIII antigen were prepared from guinea pig plasma with a cross-reacting rabbit anti-human Factor VIII. Monospecific antisera to guinea pig Factor VIII antigen were produced in rabbits by using these washed immunoprecipitates as immunogens. The resulting antisera to guinea pig Factor VIII antigen detected Factor VIII antigen in guinea pig plasma and inhibited the von Willebrand factor activity in guinea pig plasma. This antibody also detected Factor VIII antigen in a solubilized protein mixture prepared from isolated cultured guinea pig megakaryocytes. Cultured guinea pig megakaryocytes were labeled with radio-active leucine. By radioautography, 96.2% of the radio-activity was present in megakaryocytes. The radio-active Factor VIII antigen present in the solubilized cell protein mixture was isolated by immunoprecipitation and characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The results demonstrate that cultured guinea pig megakaryocytes synthesize Factor VIII antigen which contains the same polypeptide subunit (mol wt 200,000) present in guinea pig plasma Factor VIII antigen.
Images
PMCID: PMC372440  PMID: 70434
19.  Sweet Chestnut (Castanea sativa Mill.) Bark Extract: Cardiovascular Activity and Myocyte Protection against Oxidative Damage 
This work was aimed at evaluating the cardioprotective effects of Castanea sativa Mill. (CSM) bark extract characterized in its phenolic composition by HPLC-DAD-MS analysis. The study was performed using primary cultures of neonatal rat cardiomyocytes to investigate the antioxidant and cytoprotective effects of CSM bark extract and isolated guinea pig left and right atria, left papillary muscle, and aorta to evaluate its direct effect on cholinergic and adrenergic response. In cultured cardiomyocytes the CSM bark extract reduced intracellular reactive oxygen species formation and improved cell viability following oxidative stress in dose-dependent manner. Moreover, the extract decreased the contraction induced by noradrenaline (1 μM) in guinea pig aortic strips and induced transient negative chronotropic and positive inotropic effects without involvement of cholinergic or adrenergic receptors in the guinea pig atria. Our results indicate that CSM bark extract exhibits antioxidant activity and might induce cardioprotective effect.
doi:10.1155/2013/471790
PMCID: PMC3600200  PMID: 23533692
20.  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
21.  COMPLEMENT AS A MEDIATOR OF INFLAMMATION  
Interaction in free solution of highly purified preparations of human C'1 esterase, C'4, C'2, and C'3, in the presence of Mg2+, resulted in rapid generation of an activity indistinguishable by biological criteria from anaphylatoxin. The formation of anaphylatoxin was associated with immunoelectrophoretic conversion of C'3 to anodically faster migrating proteins and was unaffected by the presence or absence of added C'5. The biological properties of human anaphylatoxin prepared in this manner include: contraction and desensitization of isolated guinea pig ileum, failure to contract isolated rat uterus, enhancement of vascular permeability in guinea pig skin, degranulation of mast cells in guinea pig mesentery preparations, and liberation of histamine from suspensions of rat peritoneal mast cells. The smooth muscle-contracting and permeability enhancing properties were fully blocked by an antihistaminic drug, triprolidine. No cross-desensitizing activity on guinea pig ileum was demonstrable between rat and human or guinea pig and human anaphylatoxins but a closer biological relationship between rat and guinea pig anaphylatoxins was observed. It is concluded that anaphylatoxin is a product of the complement system. Its possible relationship to apparently similar activities currently being obtained in other laboratories has been discussed.
PMCID: PMC2138204  PMID: 4960742
22.  Spasmolytic activity of a herbal drug isolated from Tephrosia purpurea in guinea pigs 
Ancient Science of Life  2004;23(4):59-65.
We investigated the spasmolytic activity of herbal drugs isolated from Tephrosia purpurea on guinea pigs for the treatment of asthma in India. For this investigation, the herbal drug was extracted with 70% ethanol in soxhlet apparatus. After purification and isolution, the drug was used in experimental animals to observe prophylactic activity. For anaphylactic activity, horse serum 0.5 ml along with triple antigen (0.5 ml) was induced in guinea pigs. To observe prophylactic activity, male guinea pigs weighing about 250-450 gms were killed by cervical dislocation and the trachea was isolated. Each trachea was cut in to six segments. Each segment consists of three cartilage rings. Each end of tracheal muscles was attached to the bronchospasm transducers for isometric recording of the tension charges on a polygraph. The results of experiments clearly showed the spasmolytic activity of the drug. The preliminary phytochemical investigation, however shows the presence of glycoside saponins.
PMCID: PMC3330980  PMID: 22557142
Tephrosia purpurea; spasmolytic; polygraph; Bronchospasm
23.  Contractile effects of bacterial cell walls, their enzymatic digests, and muramyl dipeptides on ileal strips from guinea pigs. 
Infection and Immunity  1982;35(2):612-619.
Cell walls isolated from four bacterial species (Streptococcus pyogenes, Lactobacillus plantarum, Streptomyces gardneri, and Nocardia corynebacteriodes), which exhibited the adjuvant effect of stimulating cellular and humoral immune responses against ovalbumin in guinea pigs, caused the slow-starting and long-lasting contraction of guinea pig ileal strips suspended in Tyrode solution. In contrast to these cell walls active in immunoadjuvancy, those isolated from five bacterial species (Micrococcus lysodeikticus, Staphylococcus epidermidis, Arthrobacter atrocyaneus, Corynebacterium insidiosum, and Ampullariella regularis), which lacked immunoadjuvancy at least in intact walls, caused no or very weak contraction of the ileal strips. Further study demonstrated that both a monomer and a polymer of disaccharide-stem peptides, which were obtained by enzymatic degradation of S. epidermis cell wall peptidoglycans, displayed similar contractile effects. It was finally revealed that guinea pig ileum strips showed a definite contractile response to N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) and 6-O-stearoyl- and 6-O-(2-tetradecylhexadecanoyl)-MDPs, but not to their analogs, whose C-terminal amino acid was L-isoglutamine or D-isoasparagine in place of D-isoglutamine and which lacked adjuvancy. 6-O-(3-Hydroxy-2-docosylhexacosanoyl)-MDP, on the other hand, caused a slow and lasting relaxation of the ileum strips, but its L-isoglutamine and D-isoasparagine analogs did not.
PMCID: PMC351085  PMID: 7056578
24.  Transport of Salt and Water in Rabbit and Guinea Pig Gall Bladder 
A simple and reproducible method has been developed for following fluid transport by an in vitro preparation of mammalian gall bladder, based upon weighing the organ at 5 minute intervals. Both guinea pig and rabbit gall bladders transport NaCl and water in isotonic proportions from lumen to serosa. In the rabbit bicarbonate stimulates transport, but there is no need for exogenous glucose. The transport rate is not affected by removal of potassium from the bathing solutions. Albumin causes a transient weight loss from the gall bladder wall, apparently by making the serosal smooth muscle fibers contract. Active NaCl transport can carry water against osmotic gradients of up to two atmospheres. Under passive conditions water may also move against its activity gradient in the presence of a permeating solute. The significance of water movement against osmotic gradients during active solute transport is discussed.
PMCID: PMC2195407  PMID: 14212148
25.  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

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