Tracheal Chain Research Articles

Protective Effects of Icosahydropicenic Acid Isolated from the Roots of Clerodendrum serratum (L) Moon on Experimental Allergic Asthma

Plant saponins are widely distributed amongst plants and have a wide range of biological properties. Icosahydropicenic acid (IHPA), a new pentacyclic triterpenoid saponin was first time isolated from the roots of Clerodendrum Serratum (L) Moon (Verbenaceae). IHPA, at the dose of 100mg/kg, showed significant protection of mast cell degraualtion (59.62%) as compared to standard sodium cromoglycate (64.48%). The compound also revealed significant inhibitory activity on histamine—induced goat tracheal chain preparation. The study provides scientific basis for its clinical use in the treatment of asthma.

Investigation Into the Mechanism of Anti-Asthmatic Action of Moringa oleifera

ABSTRACT.We have studied the possible mechanism of the antiasthmatic action of Moringa oleifera seed kernel ethanolic extract (EXMO, 400 mg/kg). EXMO produced an increase in the Preconvulsion Dyspnea time induced by histamine and acetylcholine aerosol, a significant reduction in the elevated eosinophil and monocyte counts in the Broncho-Alveolar Lavage fluid of sensitized guinea pigs, reduction in the paw edema volume as compared to the control rats, and decrease in the elevated histamine release from the sensitized guinea pig lungs. The pD2 values of histamine in tracheal chain and taenia coli were significantly greater and that in lung strip was lower in the sensitized animals and treatment with EXMO significantly decreased pD2 values in all three preparations. Our data suggest inhibition of the immediate hypersensitive reaction, histamine release, and the infiltration of various inflammatory cells as possible antiasthmatic mechanisms of action.

Investigation into the mechanism of anti-asthmatic action of Lepidium sativum

We have studied the possible mechanism of anti-asthmatic action of ethanolic extracts of dried seeds of Lepidium sativum (EXLS, 400 mg/kg) using various experimental models. EXLS produced an increase in the Pre-Convulsion Dyspnoea time induced by histamine and acetylcholine aerosol, a significant reduction in the elevated leucocyte counts in the Broncho-Alveolar Lavage fluid of sensitized guinea-pigs and reduction in the paw edema volume as compared to the control rats. Treatment with EXLS also produced decrease in the elevated histamine release from the sensitized guinea-pig lungs. The anti-asthmatic anti-inflammatory responses of EXLS was supported by improvement in microscopic changes like infiltration of inflammatory cells, submucosal edema, epithelial desquamation and reduced lumen size of the bronchi. The <TEX>$pD_2$</TEX> values of histamine in tracheal chain and taenia-coli were significantly greater and that in lung strip was lower in the sensitized animals as compared to control. Treatment of sensitized guinea pigs with EXLS significantly decreased <TEX>$pD_2$</TEX> values of histamine in all three preparations. Our data suggest the prevention of hyper-responsiveness in bronchial smooth muscles and inhibition of the immediate hypersensitive reaction, histamine release in the lungs and the infiltration of various inflammatory cells as the possible mechanisms of anti-asthmatic activity of EXLS.

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.

Evaluation of antiasthmatic activity ofCurculigo orchioidesgaertn. 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.

Antiasthmatic potential of aqueous extract of Cassia occidentalis

Asthma is a chronic inflammatory disease of the airways characterized by the fibrosis of the airways, hyperplasia and hypertrophy of smooth muscle cells and mucus secretary cells due to infiltration of activated eosinophils and activation of mast cells and lymphocytes. Various traditional medicinal plants have been used in folk medicine to treat a wide range of physical ailments such as asthma and bronchitis. Cassia occidentalis L. (Caesalpiniaceae) leaf juice is traditionally used for the treatment of the respiratory tract ailments and is well-known drug in Ayurvedic and Unani system of medicine. This plant is abundant in the region of North Maharashtra commonly known as Kasmardan. Since no scientific studies have been carried out on the leaf the present study evaluates the antiasthmatic activity an aqueous extract of C. occidentalis (COAE) on in vitro and in vivo animal models. In vitro studies carried out on histamine- induced contraction in isolated goat tracheal chain and in vivo studies on milk- induced eosinophilia, mast cell degranulation and capillary permeability in mice (n=5). The results showed that aqueous extract of C. occidentalis inhibited the contractile effect of histamine (P<0.05). A dose dependent contraction of goat tracheal chain is observed. Treatment with COAE (200mg/ kg, i.p.) decreased eosinophilia by 71% while mast cells were protected 66% from degranulation as compared to control group. Also, COAE decreased capillary permeability by 69% in mice was evident from its effect on optical density of the dye. Thus, COAE showed antihistaminic, mast cell stabilizing and decreasing capillary permeability effect and hence possesses potential role in the treatment of asthma.

Synthesis and Structure-Activity Relationships of Vasicine Analogues as Bronchodilatory Agents

The series of vasicine (1) analogues, an alkaloid from Adhatoda vasica Nees., were synthesized with changes in A, B or C rings. Compounds 13-19 were evaluated for in vitro bronchodilatory activity using isolated guinea pig tracheal chain. Compounds 3-8 were also synthesized in good yields using microwave-mediated synthesis under solvent free conditions. Compounds 5 and 8 with seven-member C ring were more active than etofylline and caused 100% relaxation of both the histamine and acetycholine pre-contracted guinea pig tracheal chain. The structure-activity relationship studies showed that the quinazoline and oxo functionalities were essential for activity. The compounds without C ring and instead having aliphatic and phenyl substitutions in B ring showed relaxation against histamine pre-contracted tracheal chain only, 2-methyl substituted analogues, 12 and 13, being most active with 100% relaxation effect.

Mechanisms of the contractile effect of the alcoholic extract of Aegle marmelos Corr. on isolated guinea pig ileum and tracheal chain

In the present work, the effect of the alcoholic extract of the leaves of Aegle marmelos Corr. on guinea pig isolated ileum and tracheal chain was investigated, as this plant is used traditionally to treat asthma and related afflictions. These effects were investigated using the isolated organ bath method. 1 mg/ml and 2mg/ml doses of the alcoholic extract of this plant produced a positive relaxant effect in isolated guinea pig ileum and tracheal chain, respectively. In addition, they antagonized the contractions, which are produced by histamine. Because the alcoholic extracts elicited the antagonistic effect against histamine and also relaxed the histamine-induced contractions, it can be concluded that relaxations induced by A. marmelos in both guinea pig ileum and tracheal chain were due to the depression of H1-receptors. Since we observed a complete relaxation of the guinea pig ileum and tracheal chain produced by the extract, we investigated its antagonistic effect against histamine. These results were due to the presence of one or more anti-histaminic constituents present in the alcoholic extract of this plant, therefore supporting to the traditional use of A. marmelos in asthmatic complaints.

Effect of ethanolic extract of some anti-asthmatic herbs on clonidine and haloperidol-induced catalepsy in mice

The ethanolic extract of some medicinal plants having anti-asthmatic activity such as Solanum xanthocarpum, Curcuma longa, Glycyrrhiza glabra, Piper longum, A. vasica, A. lebbeck, and Tinospora cordifolia was evaluated for antihistaminic and anti-cataleptic activity. The aqueous solution of ethanolic extract of S. xanthocarpum and G. glabra potentiated histamine-induced tracheal chain contractions. Whereas, C. longa, P. longum, and T. cordifolia, and A. lebbeck were without any significant effect on histamine. Only A. vasica inhibited histamine-induced tracheal chain contraction. G. glabra per se produced contraction of the tracheal chain, which was blocked by pretreatment with atropine. Single dose of S. xanthocarpum potentiated clonidine-induced catalepsy but on repeated doses (once in a day for 3 days) inhibited catalepsy. Pretreatment with ethanolic extract of C. longa, P. longum, T. cordifolia inhibited catalepsy whereas G. glabra and A. lebbeck significantly potentiated clonidine-induced catalepsy. None of the extracts inhibited haloperidol-induced catalepsy. Thus the extracts having antihistaminic activity or mast cell stabilizing activity inhibited clonidineinduced catalepsy.

Synthesis and Bronchodilatory Activity of Some Nitrogen Bridgehead Compounds.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis and bronchodilatory activity of some nitrogen bridgehead compounds

A series of tricyclic nitrogen bridgehead compounds 7– 22 have been synthesised and evaluated for their in vitro bronchodilatory activity using isolated guinea pig tracheal chain, precontracted with acetylcholine. The relaxant effect of 2,3,4,5-tetrahydroazepino[2,1- b]-8,9-dimethoxyquinazolin-11(1 H)-one ( 7) (DPJ-386) was greater than that of theophylline, aminophylline and quinazoline derivative 3, which lacks methoxy groups at positions 8 and 9. Various nitrogen containing functionalities such as benzylamino, acetamido, benzamido and phthalimido were also introduced at 9 position of 3. This resulted in loss of relaxation activity in precontracted guinea pig tracheal chain. These results show that the better relaxation property possessed by compound 7 hydrochloride is due to methoxy groups at 8 and 9 positions.

Effect of gammalinolenic acid, dihomogammalinolenic acid, ascorbyl-6-gammalinolenic acid and ascorbyl-6-dihomo gammalinolenic acid on histamine- and methacholine-induced contraction of the isolated guinea pig tracheal chain

The relaxant effects of gammalinolenic acid (GLA) and dihomo gammalinolenic acid (DGLA) were compared to the relaxant effect of arachidonic acid (AA). The effect of the combination of ascorbate to form the novel drugs ascorbyl-6-gammalinolenic acid (ascorbyl-6-GLA) and ascorbyl-6-dihomo gammalinolenic acid (ascorbyl-6-DGLA) were investigated and the role of the epithelial cells was determined. Salbutamol was used as control. The isolated tracheas of six to eight guinea pigs were used in each experiment and suspended in organ baths filled with Krebs-Henseleit solution and aerated with 95% O 2 and 5% CO 2. The relaxant effects produced for histamine-contracted preparations were as follows: AA = 71.2 ± 0.2%, GLA = 55.2 ± 4.2%, DGLA = 69.8 ± 3.9%, ascorbyl-6-GLA = 26.2 ± 5.1% and ascorbyl-6-DGLA = 54.5 ± 2.4%. For methacholine-contracted preparations: AA = 46.6 ± 3.2%, GLA = 55.0 ± 9.5%, DGLA = 61.8 ± 2.7%, ascorbyl-6-GLA = 40.0 ± 8.0% and ascorbyl-6-DGLA = 88.0 ± 15.3%. Ascorbyl-6-GLA and ascorbyl-6-DGLA had mainly a decreased relaxant effect compared to GLA and DGLA, except ascorbyl-6-DGLA after methacholine-induced contraction, which showed a significant increased relaxant effect. The removal of the epithelium showed decreased relaxant effects for the drugs except AA, which showed increased values after methacholine contraction. Histamine-contracted preparations showed varied results. Ascorbyl-6-GLA showed an increased relaxant effect, DGLA was unaffected with no additional effect, and AA, GLA and ascorbyl-6-DGLA showed decreased relaxant effects. In conclusion, it is clear that the contractant and the availability of epithelial cells could ultimately determine the results, though the mechanism remains very complex. The benefit of added ascorbate is still unclear and warrants more investigation.

Evaluation of Nigerian traditional medicine: effects of Gakani, a herbal anti-asthmatic drug

The anti-asthmatic potential of Gakani, a popular herbal drug in Nigeria was investigated. The LD 50 values of the freeze-dried aqueous extract in mice and rats were 20.9 ± 2.4 mg/kg and 18.6 ± 4 mg/kg, respectively. The extract unsurmountably blocked the effects of histamine and isoprenaline on the guinea pig tracheal chain. It produced initial dose-related contractions of the isolated guinea pig ileum and rat stomach strip, which was followed by persistent autoinhibition and inhibition of histamine- and 5-hydroxytryptamine (5-HT)-induced responses of the two preparations, respectively. The extract had good anti-inflammatory effect in rats, causing a dose- related inhibition of the increase in the paw circumference (acute inflammation) induced by subplantar injection of fresh egg albumin. These results highlight the anti-asthmatic and toxic potential of this preparation and the need for a systematic approach in the study of traditional medicines.

The Bronchodilatory Effect of 7, 9′, 7, 9-Bisepoxylignans on Guinea-Pig Isolated Trachea

Abstract A total of 8 purified 7, 9′, 7′, 9-bisepoxylignans were evaluated for bronchodilatory effect. (+)-Phillygenin was the most potent lignan and it relaxed the guinea-pig isolated tracheal chain preparation dose-dependently. The lignans potencies were compared by EC50 values.

Development of bioactive functions in hydrangeae dulcis folium. V. On the antiallergic and antimicrobial principles of hydrangeae dulcis folium. (2). Thunberginols C, D, and E, thunberginol G 3'-O-glucoside, (-)-hydrangenol 4'-o-glucoside, and (+)-hydrangenol 4'-O-glucoside.

Following the characterization of thunberginols A, B, and F, six bioactive principles, thunberginols C, D, and E, thunberginol G 3'-O-glucoside, (-)-hydrangenol 4'-O-glucoside, and (+)-hydrangenol 4'-O-glucoside, were isolated from Hydrangeae Dulcis Folium, the processed leaves of Hydrangea macrophylla SERINGE var. thunbergii MAKINO, together with four kaempferol and quercetin oligoglycosides. Their chemical structures have been determined on the basis of chemical and physicochemical evidence. Thunberginols C, D, E, and G and (-)-hydrangenol 4'-O-glucoside showed antiallergic activity in the in vitro bioassay using the Schultz-Dale reaction. These components also exhibited inhibitory activities on the histamine release from rat mast cells and on the histamine-induced contraction in isolated guinea pig tracheal chain. In addition, thunberginols C, D, E, and G showed antimicrobial activities against oral bacteria.

Histamine-like Activity of Albizia anthelmintica

The aqueous fraction of methanol extract of Albizia anthelmintica stimulated guinea pig ileum, guinea pig tracheal chain and relaxed the spontaneously contracting rat uterus. These effects were blocked by H 1 and H 2 antagonists chlorpheniarmine and ranitidine respectively which indicate histamine-like activity. The presence of histamine was confirmed by TLC analysis.

Constituents of some Asian medicinal plants

Abstract

Evaluation of ICI D7114, a putative stimulant of brown adipocytes, on histamine‐contracted guinea‐pig ileum

1. Experiments were performed to characterize the effects of the novel brown adipocyte stimulant, ICI D7114, in the guinea-pig isolated ileum, right atrium and tracheal chain. In the ileum, agonist-induced inhibition of the contractile response to either histamine or prostaglandin E2 (PGE2) was assessed, along with effects on resting rate in the atrium and resting tone in the tracheal chain. In the latter two preparations, antagonism of isoprenaline-induced responses by ICI D7114 was also assessed. 2. Inhibitory responses were obtained in the ileum to ICI D7114, isoprenaline, BRL37344, and noradrenaline. The responses to ICI D7114, isoprenaline and BRL37344 were resistant to blockade with propranolol (5 microM), naloxone (1 microM), methysergide (0.1 microM), cimetidine, indomethacin and 8-phenyltheophylline (all 10 microM). These responses to isoprenaline, in the presence of propranolol (5 microM), were competitively antagonized by alprenolol (1-100 microM) with a pA2 value of 6.44. The responses to ICI D7114 and BRL37344 were antagonized by single concentrations of alprenolol (1 microM) with apparent pKB values of 6.53 and 6.57 respectively. These data indicate an effect of ICI D7114 at the atypical beta-adrenoceptor in the guinea-pig ileum. 3. The order and relative potency of agonists at the atypical beta-adrenoceptor was BRL37344 (4) < isoprenaline (1) = ICI D7114 (1.1) > noradrenaline (0.5). 4. ICI D7114 (1 nM - 10 microM) caused no significant change in the rate of beating or the resting tone of the guinea-pig right atrium or tracheal chain respectively. It did, however, cause selective blockade of the responses to isoprenaline in these tissues (apparent pKB values 7.63 and 5.85 in atrium and tracheal chain respectively). Responses to histamine (atrium) and aminophylline (tracheal chain) were not significantly affected by 10 microM ICI D7114.5. These results demonstrate that ICI D7114 possesses selective agonist activity at atypical beta-adrenoceptors in the guinea-pig ileum and its use as a tool may help to establish a role for the atypical beta-adrenoceptor in the control of gastrointestinal motility.

Investigation of the antispasmodic potential of Hibiscus sabdariffa calyces

Addition of an aqueous extract of Hibiscus sabdariffa calyces (2.5 ml bath ≈ 125 mg of starting crude material) inhibited the tone of various isolated muscle preparations (rabbit aortic strip, rhythmically contracting rat uterus, guinea-pig tracheal chain and rat diaphragm). Other muscles were stimulated (quiescent rat uterus and frog rectus abdominis). Intravenous injection of the extract to anaesthetized cats lowered the blood pressure in a dose-response manner. The inhibitory effects were resistant to a number of standard receptor blockers but the hypotensive influence was partially blocked by atropine and the tonic effects on rat uterus were partially reduced by hydrocortisone and indomethacin.

The pharmacology of L-670,596, a potent and selective thromboxane/prostaglandin endoperoxide receptor antagonist

L-670,596 ((-)6,8-difluoro-9-rho-methylsulfonyl benzyl-1,2,3,4- tetrahydrocarbazol-1-yl-acetic acid) has been shown to be a potent receptor antagonist as evidenced by the inhibition of the binding of 125I-labeled PTA-OH to human platelets (IC50, 5.5 x 10(-9) M), inhibition of U-44069 induced aggregation of human platelet rich plasma (IC50, 1.1 x 10(-7) M), and competitive inhibition of contractions of the guinea pig tracheal chain induced by U-44069 (pA2,9.0). The compound was also active in vivo as shown by inhibition of arachidonic acid and U-44069 induced bronchoconstriction in the guinea pig (ED50 values, 0.04 and 0.03 mg/kg i.v., respectively), U44069 induced renal vasoconstriction in the pig (ED50, 0.02 mg/kg i.v.), and inhibition of ex vivo aggregation of rhesus monkey platelets to U-44069 (active 1-5 mg/kg p.o.). The selectivity of the compound was indicated by the failure to inhibit, first, ADP-induced human or primate platelet aggregation and, second, bronchoconstriction in the guinea pig in vivo and contraction of the guinea pig tracheal chain in vitro to a variety of agonists. It is concluded that L-670,596 is a potent, selective, orally active thromboxane A2/prostaglandin endoperoxide receptor antagonist.