Guinea Pig Tracheal Chains Research Articles

Possible Mechanism(s) of the Relaxant Effects of Achillea wilhelmsii on Guinea-Pig Tracheal Chains.

Achillea wilhelmsii have been used in folk remedies. The relaxant effects of the extract of A. wilhelmsii on tracheal chains of guinea pigs were examined. The relaxant effects of four cumulative concentrations of the extract, theophylline and saline were examined by their relaxant effects on precontracted tracheal chains of guinea pig by KCl (group 1), 10 μM methacholine (group 2), incubated tissues by atropine, propranolol and chlorpheniramine and contracted by KCl (group 3) and incubated tissues by propranolol and chlorpheniramine and contracted by methacholine (group 4). In group 1 and 2, all concentrations of theophylline and three higher concentrations (4, 6 and 8 mg/mL) of the extract showed significant relaxant effects compared to that of saline. In groups 3 and 4 experiments also all concentrations of the extract showed significant relaxant effects compared to that of saline. The relaxant effect of three higher concentrations (4, 6 and 8 mg/mL) of the extract in group 1 were significantly greater than those of group 2 and in group 3 were significantly lower than those of group 1. There were significant positive correlations between the relaxant effects and concentrations for theophylline in groups 1 and 2 and the extract in all four groups of experiments. These results showed a potent relaxant effect for the extract from A. wilhelmsii on tracheal chains of guinea pigs. A muscarinc receptor blockade was also suggested for the extract.

Some Pharmacodynamic Aspects of Cefepime.

Some pharmacodynamic effects of cefepime, a new injectable semisynthetic cephalosporin, were studied in laboratory animals and the following results were obtained. Cefepime maximally stimulated isolated guinea pig's ileum, rat's colon (80 μg/mL bath), and rabbit's duodenum (400 μg/mL bath). Contrarily, complete relaxation of isolated rat's fundic strip was produced by 80 μg/mL bath. Effects of cefepime on isolated rat's uterine muscle were different according to stage of sex cycle. Cefepime did not induce any effects on the resting tonus of isolated guinea pig's tracheal chain and rabbit's aortic strip. Concentrations of 200 and 400 μg/mL bath induced marked inhibition in the force of muscular twitches of the isolated frog's gastrocnemius muscle which was less potent than that induced by procaine hydrochloride 2%. Cefepime completely blocked the neuromuscular transmission of frog's rectus abdominis muscle (40 μg/mL bath) and rat's phrenic nerve hemidiaphragm preparation (200 μg/mL bath). This blockade was reversed by acetylcholine and neostigmine. Cefepime produced dose-dependent negative inotropic effect on isolated rabbit's heart and guinea pig's auricles. There were no changes in blood pressure and rate of respiration in anaesthetized dog after cefepime injection. These findings indicate that cefepime has a low potential to produce adverse reactions at therapeutic doses.

Synthesis, antihistaminic action and theoretical studies of (4-methoxybenzyl)(1,4,5,6-tetrahydropirimidin-2-yl)amine hydroiodide

In this study, (4-methoxybenzyl)(1,4,5,6-tetrahydropyrimidin-2-yl)amine hydroiodide (2) was synthesized by reaction of 2-methylmercapto-1,4,5,6-tetrahydropyrimidine hydroiodide (1) and 4-methoxybenzylamine. The synthesized compound was tested for its in vitro H1-antihistaminic activity on guinea pig trachea. A promising bronchorelaxant effect of 2 was observed in histamine-contracted guinea pig tracheal chain via H1 receptor antagonism. In addition, the molecular geometry and gauge including atomic orbital (GIAO) 1H chemical shift values of the title compound in the ground state were calculated using the density functional method (DFT/UB3LYP) and Hartree–Fock (HF) approach using 6–311G+(d), 6–311G+(d,p), LANL2DZ, DGDZVP, and DGDZVP2 basis sets and compared with the experimental data. According to the experimental and theoretical results, HF/6–311G+(d) showed a better fit to experimental values in evaluating 1H-nuclear magnetic resonance (NMR) chemical shift values. Theoretical studies supported our findings, revealing the N12 atom as the most nucleophilic. In addition, other structures of the compound such as the aromatic ring and OCH3 group increased this property.

Investigation of Anti-Asthmatic effects of Syzyzium Cumini Flesh of the Fruit on Guinea Pig Tracheal chains and its Possible Mechanism(s)

Investigation of Anti-Asthmatic effects of Syzyzium Cumini Flesh of the Fruit on Guinea Pig Tracheal chains and its Possible Mechanism(s)

The effect of the extract of Crocus sativus and its constituent safranal, on lung pathology and lung inflammation of ovalbumin sensitized guinea-pigs

Different pharmacological effects of Crocus sativus have been demonstrated on guinea pig tracheal chains in previous studies. In the present study, the prophylactic effect of the extract of C. sativus and its constituent, safranal on lung pathology and total and differential white blood cells (WBC) of sensitized guinea pigs was examined.Guinea pigs were sensitized with injection and inhalation of ovalbumin (OA). One group of sensitized guinea pigs were given drinking water alone (group S) and three groups were given drinking water containing three concentrations of safranal (S+SA1, S+SA2 and S+SA3 groups), three groups, drinking water containing three concentrations of extract (S+CS1, S+CS2 and S+CS3 groups) and one group drinking water containing one concentration of dexamethasone (S+D group) (n=6, for all groups). The lung pathology was evaluated in control, non treated and treated sensitized groups. Total and differential WBC counts of lung lavage were also examined.All pathological indices in group S showed significant increased compared to control group (p<0.05 for lung congestion and p<0.001 for other groups). Total WBC number (p<0.001), eosinophyl percentage (p<0.001) in lung lavage and serum histamine levels (p<0.01) were also increased in sensitized animals compared to those of controls. Treatment of S animals with dexamethasone, all concentrations of the extract and safranal significantly improved lung pathological changes, most types of WBC and serum histamine levels compared to group S (p<0.05–0.001). Treatment of S group with first concentration of safranal also decreased total WBC. Treatment with safranal was more effective in improvement of most pathological changes, total and differential WBC count as well as serum histamine level (p<0.05–0.001).These results showed a preventive effect of the extract of C. sativus and its constituent safranal on lung inflammation of sensitized guinea pigs. The results also showed that the effect of the plant is perhaps due to its constituent safranal.

Relaxant effects of different fractions from Tymus vulgaris on guinea-pig tracheal chains

In previous studies, the relaxant effect of Tymus vulgaris has been demonstrated on guinea pig tracheal chains. Therefore, in the present study, the relaxant effects of n-hexane, dichloromethane, methanol and aqueous fractions of Tymus vulgaris on tracheal chains of guinea pigs were examined. The relaxant effects of four cumulative concentrations of each fraction (0.4, 0.8, 1.2 and 1.6 g%) in comparison to saline as negative control and four cumulative concentrations of theophylline (0.2, 0.4, 0.6 and 0.8 mM) were examined for their relaxant effects on precontracted tracheal chains of guinea pig by 60 mM KCl (group 1) and 10 ìÌ methacholine (group 2, n = 7 for each group). In group 1, all concentrations of the n-hexane fraction and theophylline and three last concentrations (0.8, 1.2 and 1.6 g%) of dichloromethane and two higher concentrations (1.2 and 1.6 g%) of methanol fractions showed significant relaxant effects compared to that of saline (p<0.05 to p<0.001). In group 2, all concentrations of theophylline, n-hexane and dichloromethane fractions and three concentrations (0.8, 1.2 and 1.6 g%) of methanol and two higher concentrations (1.2 and 1.6 g%) of aqueous fractions showed significant relaxant effects compared to that of saline (p<0.05 to p<0.001). In addition, with group 1, the relaxant effect of all concentrations of all fractions except the n-hexane fraction, were significantly less than those of theophylline (p<0.05 to p<0.001). The n-hexane fraction showed higher relaxant effect than theophylline. The relaxant effect of all concentrations of the n-hexane fraction and the three last concentrations (0.8, 1.2 and 1.6 g%) of dichloromethane and aqueous fractions were significantly greater in group 2 than in group 1 (p<0.05 to p<0.001). There were significant positive correlations between the relaxant effects and concentrations for theophylline and all fractions (except aqueous fraction in group 1) in both groups, but a negative correlation for the aqueous fraction in group 1 (p<0.05 to p<0.001). These results showed a potent relaxant effect for n-hexane and weaker relaxant effect for other fractions from Tymus vulgaris on tracheal chains of guinea pigs.

Experimental studies on the mast cell stabilizing and bronchorelaxant effects of UNIM-352, a polyherbal Unani preparation, with therapeutic potential in bronchial asthma

The effects of UNIM-352, a polyherbal Unani preparation, was evaluated on experimental models of mast cell degranulation and bronchoconstriction with a view to study its mechanisms of action to validate its potential use as an adjunct to conventional drug therapy of bronchial asthma. In rats immunized with ovalbumin, antigen challenge resulted in degranulation of mast cells and mortality in control vehicle treated animals, whereas animals pretreated with UNIM-352 (200 or 400 mg/kg) or prednisolone (5 mg/kg) showed significant reduction of mast cell degranulation with no mortality. In the isolated guinea pig tracheal chain preparation, UNIM-352 dose dependently inhibited the histamine induced bronchoconstriction in both normal and immunized animals. The results of these studies indicate that UNIM-352 could have mast cell stabilizing and bronchorelaxant properties, both of which could contribute to its reported beneficial effects in bronchial asthma.

Evaluation of antiasthmatic activity of ethanolic extract of Elephantopus scaber L. leaves.

Aims:The aim of study was to evaluate the scientific basis for the traditional use of Elephantopus scaber leaves.Materials and Methods:In the present study, ethanol extract of Elephantopus scaber leaves was evaluated for preliminary phytochemical screening and antiasthmatic activity using histamine and acetylcholine-induced bronchospasm, mast cell degranulation and histamine induced constriction on isolated guinea pig tracheal chain at different dose levels. Student's t-Test and Dunett's test were used for statistical analysis.Results:The result of present investigation showed that the ethanolic extract of E. scaber significantly (P<0.001) decreased the bronchospasm induced by histamine, acetylcholine and protected mast cell degranulation as compared to control groups. It also decreased the histamine induce constriction on isolated guinea pig trachea in dose-dependent manner. Phytochemical studies revealed the presence of steroids, saponin, flavonoids, and phenolic compounds in the extract.Conclusions:The present study concludes that the antiasthmatic activity of ethanolic extract of E. scaber leaves may be due to the presence of flavonoids or steroids. Antiasthmatic action of the E. scaber could be due to its antihistaminic, anticholinergic and mast-cell-stabilizing property.

Anti-cholinergic effect of Zataria multiflora Boiss on guinea pig tracheal chains

The effects of three concentrations of aqueous-ethanolic extract, 10 nM atropine and saline on muscarinic receptors were tested on two groups of non-incubated (group 1; n = 7) and incubated tracheal chains with propranolol and chlorpheniramine (group 2; n = 6). The EC50 of higher concentration of the extract (2 µg mL−1) in group 2 was significantly greater than those of group 1 (p < 0.01). The maximum response obtained in the presence of all concentrations of extract in groups 1 and 2 were lower than saline (p < 0.05 to 0.001). There were parallel rightward shifts in the concentration response curves obtained for all concentrations of the extract in group 2. There was significant and positive correlation between the concentrations and the values of EC50 in group 1 (p < 0.05) and group 2 (p < 0.001). These results indicate an anti-cholinergic effect of Zataria multiflora Boiss on the tracheal chains of guinea pigs. A β-adrenoceptor stimulatory effect for the plant was also suggested.

Inhibitory effect of Zataria multiflora Boiss and carvacrol on histamine (H1) receptors of guinea‐pig tracheal chains

The inhibitory effect of aqueous-ethanolic extract of Zataria multiflora Boiss (Labiatae) and carvacrol on histamine (H(1) ) receptors was examined on tracheal chains of guinea-pigs. The effects of three concentrations of aqueous-ethanolic extract, carvacrol, 10 nm chlorpheniramine, and saline on histamine (H(1) ) receptors were tested on three groups of guinea-pig tracheal chains as follows: incubated trachea with (i) indomethacin (n = 9), (ii) indomethacin, propranolol, and atropine (n = 7), and (iii) indomethacin and propranolol (n = 6). The EC(50) (effective concentration of histamine causing 50% of maximum response) obtained in the presence of chlorpheniramine for all concentrations of the extract and carvacrol in all three groups was significantly higher than that of saline (P < 0.001 for all cases). The EC(50) obtained in the presence of all concentrations of extract in groups 2 and 3 was lower than group 1 and in group 3 lower than group 2 (P < 0.01 to P < 0.001). However, EC(50) obtained in the presence of all concentrations of carvacrol in group 3 and two higher concentrations in group 2 was higher than that of group 1 (P < 0.01 to P < 0.001). There was no significant difference in the maximum response obtained in the presence of different concentrations of extract and carvacrol between three groups. There was a parallel rightward shift in concentration-response curves obtained in the presence of all concentrations of the extract and carvacrol in all three groups. These results indicated an inhibitory effect of Z. multiflora and its constituent carvacrol on histamine H(1) receptors.

Evaluation of antihistaminic activity of Piper betel leaf in guinea pig

Piper betel Linn. leaves were evaluated for its antihistaminic activity, commonly known as Pan, Vidyache Pan or Tamboli. P. betel has a long history of use in India being applied in multiple therapeutic activities like antibacterial, treating eczema, lymphangitis, asthma, treating rheumatism. So selected, the plant P. betel is effective in histaminic activity related diseases, but antihistaminic activity of P. betel is still not scientifically investigated. In the present study, the pharmacological evaluation of ethanolic extract and essential oil extract of leaves of P. betel Linn. has been done for their antihistaminic activity on guinea pig. In isolated guinea pig tracheal chain preparation, there was a right side shift of dose response curve (DRC) of histamine. Chlorpheniramine maleate was used as a standard drug. Moreover extracts of P. beteldisturbed histamine aerosol induce bronchoconstriction in whole guinea pig, where essential oil was more effective comparatively to ethanolic extract. Thus from the results obtained in the present investigation, it can be concluded that ethanolic extract and essential oil of P. betel Linn possess antihistaminic activity. Key words: Piper betel leaf, H1-antagonist, guinea pig.

Inhibition of histamine mediated responses by Mirabilis jalapa: confirming traditional claims made about antiallergic and antiasthmatic activity

The roots of Mirabilis jalapa are used traditionally in allergic skin disorders and asthma. The effect of an ethanol : acetone (1 : 1) extract of the roots of M. jalapa was studied for antihistaminic activity using a guinea pig tracheal chain preparation and clonidine-induced mast cell granulation in mice. Its antiallergic activity was evaluated using milk-induced eosinophilia and albumin-induced paw oedema in mice. The extract (0.5 mL of 100 mg mL−1) inhibited histamine-induced guinea pig tracheal chain contractions non-competitively. The extract (100 or 200 mg kg−1 i.p.) inhibited milk-induced eosinophilia, albumin-induced paw oedema and protected mast cells against clonidine-induced granulation. The study justified the folkloric use of M. jalapa in the treatment of allergic diseases and asthma.

Bronchospasm potentiating effect of methanolic extract of Ficus religiosa fruits in guinea pigs

The sacred tree Peepal (Ficus religiosa family: Moraceae) has numerous therapeutic utility in folk medicine. It has been reported to be used in ethno medical treatment of asthma and also in epilepsy due to its high serotonin content, which has been implicated in pathophysiology of asthma, this led us to carry out the present study. The in vivo studies of histamine induced bronchospasm in guinea pigs and in vitro isolated guinea pig tracheal chain and ileum preparation. Pre-treatment of guinea pigs with ketotifen (1 mg/kg, p.o.) has significantly delayed the onset of histamine aerosol induced pre-convulsive dyspnea, compared with vehicle control (281.8(a)±11.7 vs. 112.2±9.8). The administration of methanolic extract (125, 250 and 500 mg/kg, p.o.) did not produced any significant effect on latency to develop histamine induced pre-convulsive dyspnea. On the other hand, methanolic extract of the fruits at the doses employed (i.e., 0.5, 1 and 2 mg/ml) has significantly potentiate the EC(50) doses of both histamine and acetylcholine in isolated guinea pig tracheal chain and ileum preparation. In addition, HPLC analysis of the methanolic extract showed the presence of high amounts of serotonin (2.89%, w/w). On the basis of data, it may be concluded that Ficus religiosa fruits have been found to be ineffective against histamine induced bronchospasm in guinea pigs. In addition, methanolic extract of the fruits have shown to potentiate the bronchoconstriction induced by both histamine and acetylcholine on guinea pig tracheal chain preparation.

Effect of thymoquinone on the lung pathology and cytokine levels of ovalbumin-sensitized guinea pigs

Different pharmacological effects from Nigella sativa have been demonstrated in guinea pig tracheal chains in previous studies. In the present study, the prophylactic effects of thymoquinone on lung pathology as well as blood IL-4 and IFN-γ levels in sensitized guinea pigs were examined. Three groups of guinea pigs sensitized to ovalbumin were given drinking water alone (group S) or drinking water containing low (LTQ) or high (HTQ) concentrations of thymoquinone (groups S+LTQ and S+HTQ). The lung pathology as well as blood IL-4 and IFN-γ levels of the sensitized and the control guinea pigs were evaluated in three sensitized and one control group (n=8, for all groups). The lungs of the S group showed significant pathological changes (p<0.001). Blood IL-4 and IFN-γ levels were increased in the sensitized animals compared to those of controls (p<0.01 and p<0.001, respectively). Treatment of the S animals with thymoquinone significantly improved their pathological changes to the lung and decreased their IL-4 levels (p<0.05 to p<0.001) but increased their IFN-γ levels (p<0.001). These results showed a preventive effect of thymoquinone on lung inflammation in sensitized guinea pigs.

The effect of safranal on histamine (H 1) receptors of guinea pig tracheal chains

The effect of three concentrations of safranal on histamine (H 1) receptors was tested on two groups of tracheal chains incubated with: 1) indomethacin, and 2) indomethacin, propranolol and atropine ( n = 6). The EC 50 (effective concentration of histamine causing 50% of maximum response) obtained in the presence of chlorpheniramine and all concentrations of safranal in both groups were significantly greater than those of saline ( p < 0.05 to p < 0.001). The EC 50 obtained in the presence of all concentrations of safranal and maximum response of its two higher concentrations (1.25 and 2.5 μg/mL) in group 2 were greater than in group 1 ( p < 0.05 to p < 0.001).

The Differences in the Relaxant Effects of Different Fractions of Rosa damascena on Guinea Pig Tracheal Smooth Muscle

Objective(s) In the present study, the differences in the relaxant effects of aqueous, ethyl acetate and n-butanol fractions of Rosa damascena on tracheal smooth muscle of guinea pigs were examined. Materials and Methods The relaxant effects of three cumulative concentrations of each fraction (0.1, 0.2 and 0.4 g%) in comparison with saline and three cumulative concentrations of theophylline (0.1, 0.2, and 0.4 mM) were examined on precontracted tracheal chains of guinea pig by 60 mM KCl (group 1, n= 5) and 10 pM methacholine (group 2, n= 8). Results In group 1, all concentrations of theophylline, ethyl acetate fraction and two final concentrations of n-butanol fraction showed significant relaxant effects in comparison with saline (p< 0.05 to P< 0.001). In group 2, all concentrations of theophylline, ethyl acetate and aqueous fractions showed concentration dependent relaxant effects compared to that of saline (p< 0.01 to P< 0.001). In addition, the effect of ethyl acetate fraction in group 1 was significantly higher than those of theophylline (p< 0.05 to p< 0.001). However, the effects of other fractions were significantly lower than theophylline in both groups (p< 0.01 to p< 0.001). There were significant correlations between the relaxant effects and concentrations for theophylline and all fractions (except aqueous fractions in group 1) in both groups. Conclusion The results showed a potent relaxant effect for ethyl acetate fraction of R. damascena on tracheal smooth muscle comparable to that of theophylline but a relatively weak relaxant effect for aqueous and n-butanol fractions at concentrations used.

The Effect of Thymoquinone, the Main Constituent ofNigella sativaon Tracheal Responsiveness and White Blood Cell Count in Lung Lavage of Sensitized Guinea Pigs

In previous studies, the relaxant, anticholinergic (functional antagonism) and antihistaminic, effects of Nigella sativa have been demonstrated on guinea pig tracheal chains. In the present study, the prophylactic effect of thymoquinone (one of the constituents of Nigella sativa) on tracheal responsiveness and white blood cell (WBC) count in lung lavage of sensitized guinea pigs was examined. Four groups of sensitized guinea pigs to ovalbumin (OA) were given drinking water alone (group S), drinking water containing low or high concentrations of thymoquinone (S + LTQ and S + HTQ groups) or inhaled fluticasone propionate (FP 250 microg) twice a day (positive control group) (n = 7, for all groups). Tracheal responses of control and four groups of sensitized animals to methacholine at an effective concentration causing 50 % of maximum response (EC(50) M) were measured. Tracheal responses to 0.1 % OA, relative to contraction induced by 10 microM methacholine were also examined. Total WBC and its differential count in lung lavage were also measured. The tracheal responsiveness to methacholine, OA and WBC of S guinea pigs was significantly higher than those of controls (p < 0.001 for all cases). Tracheal responsiveness in S + LTQ, S + HTQ, and FP groups to both methacholine (p < 0.05 to p < 0.001) and OA (p < 0.001 for all cases) was significantly decreased compared to that of the S group. Total WBC was also decreased in all experimental groups compared to that of the S group (p < 0.001 for all groups). There was an increase in eosinophils and a decrease in neutrophils, lymphocytes and monocytes in the S animals compared to the controls (p < 0.001 for all cases). Treatment with both concentrations of thymoquinone and FP variably improved differential WBC count changes compared to the S animals (nonsignificant to p < 0.001). The improvement in tracheal responsiveness, total WBC, eosinophils and lymphocytes changes in the S animals treated with both concentrations of TQ were significantly greater than those of FP (p < 0.05 to p < 0.001). These results showed a preventive effect of thymoquinone, one constituent of N. sativa, on tracheal responsiveness and inflammatory cells of lung lavage of sensitized guinea pigs which was comparable or even greater than that of the inhaled steroid.

The effect of natural adjuvants on tracheal responsiveness and cell count in lung lavage of sensitized guinea pigs

Airway inflammation is a well-characterized pathological feature of asthma. The effects of two natural adjuvants on lungs of sensitized guinea pigs were examined. The responses of guinea pig tracheal chains, WBC, differential WBC in lung lavage and IL-4 and interferon (IFN)-gamma levels in serum were examined in control guinea pigs and four treatment groups, including sensitized animals (S) and sensitized animals treated with the adjuvants PC (S + PC), G2 (S + G2) or both adjuvants (S + PCG2) (n = 6). Animals were sensitized by injection and inhalation of ovalbumin. Tracheal responsiveness to methacholine (concentration of methacholine causing 50% of maximum contraction), WBC, eosinophil, neutrophil and basophil numbers were increased and lymphocyte numbers were decreased in lung lavage of sensitized animals compared with the control group (P < 0.01 to P < 0.001). However, G2 adjuvant and the combination of G2 and PC adjuvants caused a significant reduction in tracheal responsiveness (P < 0.01 and P < 0.001, respectively). In addition both adjuvants prevented changes in WBC (P < 0.001 for both). Both adjuvants and the combination prevented changes in eosinophil, neutrophil and basophil numbers in lung lavage of sensitized animals (P < 0.05 to P < 0.001). The adjuvants also prevented changes in IL-4 but increased IFN-gamma levels in all treatment groups compared with group S (P < 0.001 for all cases). These results indicate that the two natural adjuvants (especially G2 adjuvant) and their combination have therapeutic effects, with reduction in tracheal responsiveness and WBC in lung lavage of sensitized guinea pigs.

Stimulatory effect of Crocus sativus (saffron) on β2-adrenoceptors of guinea pig tracheal chains

To study the mechanism(s) of the relaxant effects of Crocus sativus (Iridaceae), the stimulatory effect of aqueous-ethanolic extracts of this plant and one of its constituent, safranal was examined on beta-adrenoceptors in tracheal chains of guinea pigs. The beta(2)-adrenergic stimulatory was tested by performing the cumulative concentration-response curves of isoprenaline-induced relaxation of pre-contracted isolated guinea pig tracheal chains. The studied solutions were included two concentrations of aqueous-ethanolic extract from Crocus sativus (0.1 and 0.2g%), safranal (1.25 and 2.5 microg), 10nM propranolol, and saline. The study was done in two different conditions including: non-incubated (group 1, n=9) and incubated tissues with 1 microM chlorpheniramine (group 2, n=6). The results showed clear leftward shifts in isoprenaline curves obtained in the presence of only higher concentration of the extract in group 1 and its both concentrations in group 2 compared with that of saline. The EC(50) (the effective concentration of isoprenaline, causing 50% of maximum response) obtained in the presence of both concentrations of the extract (0.17+/-0.06 and 0.12+/-0.02) and safranal (0.22+/-0.05 and 0.22+/-0.05) in group 1 and only in the presence of two concentrations of the extract (1.16+/-0.31 and 0.68+/-0.21) in group 2 was significantly lower compared to saline (1.00+/-0.22 and 4.06+/-1.04 for groups 1 and 2, respectively) (p<0.05-0.001). The maximum responses obtained in the presence of both concentrations of the extract and safranal in group 1 were significantly lower than that of saline (p<0.005 for all cases). All values (CR-1=(EC(50) obtained in the presence of active substances/EC(50), obtained in the presence of saline)-1) obtained in the presence of higher concentrations of extract in group 1, its both concentrations and higher concentration of safranal in group 2 were negative and there were significant differences in this value between propranolol and those obtained in the presence of extract and safranal (p<0.05 to p<0.001). The results indicated a relatively potent stimulatory effect of the extract from Crocus sativus on beta(2)-adrenoceptors which is partially due to its constituent, safranal. A possible inhibitory effect of the plant on histamine (H(1)) receptors was also suggested.

Anti-histaminic, anti-inflammatory and bronchorelaxant activities of 2, 7-dimethyl-3-nitro-4H pyrido [1,2-a] pyrimidine-4-one

An immunopharmacological profile of 2, 7-dimethyl-3-nitro-4H pyrido [1,2-a] pyrimidine-4-one (P-I) has been investigated using in vitro and in vivo models representing various features of Type I allergy. P-I prevented compound 48/80-mediated histamine release from rat peritoneal mast cells. A promising anti-inflammatory activity of P-I was evident in active paw anaphylaxis (mice) and carragenan-induced paw edema (rat). P-I inhibited eosonophil accumulation and eosinophil peroxidase activity in bronchoalveolar lavage fluid from ovalbumin challenged balb/c mice: in these animals blood levels of IL-5, and CD4 + T cells also remained attenuated. A promising bronchorelaxant effect of P-I was observed in histamine-contracted guinea pig tracheal chain via its antagonism to H1 receptor. These findings were compared with some known compounds (ketotifen, cetirizine and promethazine). The anti-histaminic, anti-inflammatory and bronchorelaxant activities of P-I has been discussed in context with its potential profile as an anti-allergic and anti-asthmatic agent.