Effect of Angelica glauca essential oil on allergic airway changes induced by histamine and ovalbumin in experimental animals.

OBJECTIVE: Angelica glauca Edgew (Apiaceae) is used in traditional medicine for treatment of several diseases including bronchial asthma. The present investigation was aimed to evaluate broncho-relaxant activity of A. glauca essential oil in histamine and ovalbumin (OVA)-induced broncho constriction in experimental animals. MATERIALS AND METHODS: Airway was induced using histamine aerosol in guinea pigs (n = 24) and OVA aerosol in albino mice (n = 24). The number of inflammatory cells, namely, absolute eosinophils count in blood, total immunoglobulin E (IgE) in serum, eosinophils, and neutrophils in bronchoalveolar lavage fluid (BALF) and histopathological examination of lung tissues were investigated in A. glauca oil and dexamethasone-treated groups. A. glauca oil 200 µL/kg was given orally, and dexamethasone 2 mg/kg was given intraperitoneal. Both the treatments were repeated daily for 7 days. Results were analyzed by one-way ANOVA, and P ≤ 0.05 was considered statistically significant. RESULTS: Treatment with A. glauca essential oil significantly (P < 0.001) increased the time of preconvulsive dyspnea in histamine-induced guinea pigs. Oral treatment of A. glauca oil significantly (P < 0.001) decreased absolute blood eosinophil count (from 325 ± 3.69 to 200 ± 3.05 cells/mm3), serum level of IgE (from 6.10 ± 0.05 to 0.70 ± 0.08 IU/L), and the number of eosinophils (from 11.0% ±1.41% to 3.0% ±0.51%), neutrophils (from 13.0% ±1.12% to 5.0% ±1.39%) in BALF. Histopathological changes observed in lungs of untreated group were marked suppressed by treatment with A. glauca oil. CONCLUSION: The essential oil of A. glauca has bronchorelaxation in both histamine and OVA-induced bronchoconstriction in animals. The traditional use of A. glauca against asthma could be attributed to its bronchodilator property as observed in the present study.

Effects of allergen exposure on methacholine and AMP-induced air trapping in pollen-sensitive subjects.

BACKGROUND: The effect of pro-inflammatory stimuli on bronchoconstrictor-induced air trapping has not been studied. OBJECTIVE: To determine the effect of natural allergen exposure, a pro-inflammatory stimulus, on methacholine- and adenosine 5'-monophospate (AMP)-induced air trapping. METHODS: Airway responsiveness to methacholine and AMP before and during the pollen season was obtained in 25 subjects with pollen allergy and in 10 healthy controls. The response was expressed by the sensitivity (PC20 value) and by the slope and intercept of the FVC values recorded at each step of the challenge against the corresponding FEV1 values. RESULTS: The slope and intercept FVC versus FEV1 values for both methacholine and AMP were significantly higher in subjects with pollen allergy than in healthy controls. In the group with pollen allergy, both methacholine and AMP PC20 values decreased significantly during the pollen season. However, the mean (95% CI) slope FVC versus FEV1 values for methacholine were 1.00 (0.84-1.16) before the pollen season and 0.99 (0.86-1.12, P = 0.90) during the pollen season. Similar results were obtained with AMP. CONCLUSIONS: Although the air trapping induced by both methacholine and AMP is significantly greater in subjects with pollen allergy than in healthy controls, natural allergen exposure is associated with a selective increase in airway sensitivity without concomitant changes in bronchoconstrictor-induced air trapping. These findings suggest that the information provided by the bronchoconstrictor-induced change in FEV1 and FVC is not equivalent and may be complementary.

[Fifty percent of pollinosis patients sensitive to birch pollen demonstrate bronchoconstriction during bronchial provocation test with the allergen]. / Polowa chorych na pylkowice, uczulonych na pylek brzozy, reaguje skurczem oskrzeli w trakcie oskrzelowego testu prowokacyjnego z alergenem.

UNLABELLED: Birch pollens are known as seasonal asthma precipitants. Our earlier studies evidenced a very high frequency of positive results bronchial allergen challenges in pollinosis patients sensitive to grass pollen. The aim of the study was to evaluate how often the bronchial challenge with birch pollen allergen causes bronchoconstriction. MATERIAL AND METHODS: Studies were performed outside of pollen season on 30 patients sensitive to birch pollen allergen. Before the allergen challenges bronchial provocation tests with methacholine were performed in all subjects. RESULTS: About 13% of examined group had bronchial hyperreactivity (PC20FEV1Mch < 8 mg/ml) and 50% demonstrated bronchoconstriction after birch pollen allergen inhalation. CONCLUSIONS: About 13 percent of patients sensitive to birch pollen demonstrated nonspecific hyperrectivity out of pollen season. Bronchial birch allergen challenge tests are positive in about half of birch sensitive patients with pollinosis.

Bronchodilatory effects of the aqueous extract of Gynostemma pentaphyllum and gypenosides III and VIII in anaesthetized guinea-pigs.

The bronchodilatory activity of the aqueous extract of Gynostemma pentaphyllum Makino leaves was investigated in anaesthetized guinea-pigs and compared with two of its isolated gypenosides (III and VIII). The results showed that the intravenous administration of the decoction of G. pentaphyllum (2.5, 5 or 10 mg kg(-1)) decreased bronchial resistance in basal conditions and significantly (P < 0.01) reduced (68% inhibition) the bronchoconstrictor action of histamine. Furthermore, the extract antagonized (80% inhibition) the bronchoconstrictor response induced by the antigen in sensitized guinea-pigs. Gypenosides III (0.7 mg kg(-1), i.v.) and VIII (0.3 mg kg(-1), i.v.) caused a similar protective effect in both experimental models used; however, the duration and the intensity of the action was less than that of the extract containing corresponding quantities of gypenosides III and VIII. This study confirmed the validity of the traditional use of this plant in the treatment of asthma and other respiratory disorders.

Adrenal influences on the inhibitory effects of procaterol, a selective Beta-two-adrenoceptor agonist, on antigen-induced airway microvascular leakage and bronchoconstriction in Guinea pigs.

While the guinea pig has been the preferred choice for use as a model of allergic bronchial asthma in the evaluation of anti-asthmatic drugs, it has been shown that antigen-induced bronchoconstriction in guinea pigs is attenuated by epinephrine released from the adrenal gland. In order to investigate the possible influence of the adrenal gland on the effects of antiexudative and bronchodilative drugs on antigen-induced airway responses, we examined the inhibitory effects of procaterol, a selective beta(2)-adrenoceptor agonist, on antigen-induced airway microvascular leakage and bronchoconstriction in adrenalectomized guinea pigs and compared them with the drug's effects in sham-operated animals. Guinea pigs sensitized passively with anti-ovalbumin (OA) guinea-pig serum were adrenalectomized or sham-operated under urethane anesthesia and examined 30 min after surgery in the following experiments. (1) Animals were intravenously administered Evans blue dye to quantify airway plasma exudation, and then OA was inhaled for 10 min while measuring pulmonary inflation pressure, a parameter of bronchoconstriction. Procaterol (1, 3, 10, or 30 microg/kg) or saline (control) was administered into the airways 10 min prior to OA inhalation. The amount of extravasated Evans blue dye in the airways was calculated. (2) Venous blood samples were collected during OA or saline inhalation and plasma catecholamine levels were compared. In control animals, OA-induced increases in both the amount of Evans blue dye and in pulmonary inflation pressure were markedly greater in adrenalectomized animals than in sham-operated animals. Procaterol dose-dependently inhibited OA-induced airway microvascular leakage and bronchoconstriction, and its effects were more potent in adrenalectomized animals (significant at 1 microg/kg and higher) than in sham-operated animals (significant at 10 microg/kg and higher). Although the plasma concentration of epinephrine during OA inhalation was approximately 3 times higher than that during saline inhalation in sham-operated animals, no difference was seen in adrenalectomized animals. In conclusion, while procaterol essentially possesses pronounced inhibitory effects on antigen-induced airway microvascular leakage and bronchoconstriction in guinea pigs, the effects are considerably masked by epinephrine released from the adrenal gland.

Neurokinin-1 receptor mediates stress-exacerbated allergic airway inflammation and airway hyperresponsiveness in mice.

BACKGROUND: A wealth of clinical observation has suggested that stress and asthma morbidity are associated. We have previously established a mouse model of stress-exacerbated allergic airway inflammation, which reflects major clinical findings. OBJECTIVE: The aim of the current study was to investigate the role of the neurokinin- (NK-)1 receptor in the mediation of stress effects in allergic airway inflammation. METHODS: BALB/c mice were systemically sensitized with ovalbumin (OVA) on assay days 1, 14, and 21 and repeatedly challenged with OVA aerosol on days 26 and 27. Sound stress was applied to the animals for 24 hours, starting with the first airway challenge. Additionally, one group of stressed and one group of nonstressed mice received the highly specific NK-1 receptor antagonist RP 67580. Bronchoalveolar lavage fluid was obtained, and cell numbers and differentiation were determined. Airway hyperreactivity was measured in vitro by electrical field stimulation of tracheal smooth-muscle elements. RESULTS: Application of stress in sensitized and challenged animals resulted in a significant increase in leukocyte number in the bronchoalveolar lavage fluid. Furthermore, stressed animals showed enhanced airway reactivity. The increase of inflammatory cells and airway reactivity was blocked by treatment of animals with the NK-1 receptor antagonist. CONCLUSION: These data indicate that the NK-1 receptor plays an important role in mediating stress effects in allergen-induced airway inflammation.

Effects of Ding-Chuan-Tang on bronchoconstriction and airway leucocyte infiltration in sensitized guinea pigs.

Ding-Chuan-Tang (DCT), a traditional Chinese medicine, has been used in treatment of the bronchial asthma for several centuries. However, the therapeutic mechanism of these Chinese medicine are still far from clear. To understand the mechanism of antiasthmatic property of DCT. A guinea pig model of allergic asthma was used to investigate the effects of DCT on ovalbumin-induced early and late asthmatic responses and airway inflammation, particularly the extent of eosinophil infiltration, and examine it direct beta2-adrenoceptor agonist activity in guinea-pig isolated trachea. We had used three different protocals in ovalbumin sensitized guinea pigs by administrating 10 g/kg of DCT extracts to sensitized guinea pigs 30 min before antigen challenge (group I), 5 hr after antigen challenge (group II) and 2.5 g/kg once daily from the day of sensitization to the day of challenge. Our result showed that administration of DCT singificantly inhibited the antigen induced immediate asthmatic responses (IAR) in group I and inhibited both IRA and late asthmatic responses (LAR) in actively sensitized guinea pig in group III. DCT caused concentration-dependent relaxations in strips of guinea pig trachea contracted with carbachol, however ICI-118551, a selective beta2-adrenoceptor antagonist, didn't significantly competitively inhibit the relaxations caused by DCT. Furthermore, examination of bronchoalveolar lavage fluid (BALF) revealed that DCT significantly inhibited the increase in percent of eosinophils in the airway after antigen challenge in three group. Histopathologic examination showed DCT suppressed the eosinophil infiltration into lung tissue. These results suggest that the antiasthmatic effect of DCT is mainly due to its bronchodilatation effect and its ability to inhibit the eosinophil into the airway and there is prophylactic effect of DCT on allergen-induced airway inflammation.

Effects of saiboku-to on dual-phase bronchoconstriction in asthmatic guinea pigs.

In recent years, bronchial asthma has come to be regarded pathologically as a chronic inflammatory disease of the respiratory tract. Inhalational steroids and antiinflammatory drugs are recognized as being effective against bronchial asthma. In this study, the effects of Saiboku-to, a Chinese herbal (Kampo) formulation, were investigated on asthmatic guinea pigs sensitized to ovalbumin (OA). Following 7-day administration of Saiboku-to (500 micrograms/kg), the late asthmatic response (LAR) to an antigen challenge was found to be inhibited. The number of eosinophils in fluid obtained by bronchoalveolar lavage (BAL) 4 h after antigen challenge was decreased while the infiltration of eosinophils and T-lymphocytes into the lung parenchyma was inhibited. These findings suggest that Saiboku-to has the potential to become a useful drug in the treatment of bronchial asthma.

Characterization of 5-lipoxygenase inhibitors in biochemical and functional in vivo assays.

Several potent and selective inhibitors of 5-lipoxygenase (5-LO) have been recently developed with excellent activity in certain in vivo assays of leukotriene production. The efficacy of three such inhibitors that have been in clinical trials (zileuton, A-78773 and ZD2138) were evaluated in: 1) ex vivo whole blood assay, 2) dermal Arthus reaction, and 3) functional airway response. In addition, a model of eicosanoid production in rat lung was developed that provides a simple assay for evaluation of the biochemical efficacy of 5-LO inhibitors in the lung. Bronchoalveolar lavage of rat lung with calcium ionophore A23187 resulted in rapid and robust production of PGE2, 6-keto-PGF1 alpha, thromboxane (TxB2), and leukotriene B4 (LTB4). Supplementation of lavage fluid with archidonic acid markedly augmented production of all eicosanoids except LTB4. All three inhibitors were potent and selective blockers of LTB4 production in the ex vivo whole blood assay and in the dermal Arthus reaction. In contrast, higher doses of inhibitor were needed to block LTB4 production in the rat lung lavage model than were needed to block ex vivo whole blood LTB4 production when both end points were measured in the same animal. Similarly, zileuton and A-78733 were less effective in suppressing the functional airway response to antigen in sensitized guinea pigs, whereas both inhibitors were effective in suppressing LTB4 production in the ex vivo whole blood assay. These results demonstrate that different 5-LO inhibitors have markedly distinct efficacy for inhibition of leukotriene production, depending on the animal model.(ABSTRACT TRUNCATED AT 250 WORDS)

Capsaicin pre-treatment prevents the development of antigen-induced airway hyperresponsiveness in neonatally immunised rabbits.

The effect of a 3-day pre-treatment regime of capsaicin (8-methyl-N-vanillyl-6-nonenamide) (80 mg/kg s.c.) on airway changes induced by Alternaria tenuis aerosol challenge 3 days later was assessed in adult rabbits immunised from birth to the age of 3 months. Pre-treatment with capsaicin did not alter basal lung function or basal responsiveness to inhaled histamine. While capsaicin had no significant effect on the acute bronchoconstriction induced by antigen, this dose was sufficient to significantly inhibit the increase in airway responsiveness to inhaled histamine achieved 24 h following antigen challenge. The pulmonary recruitment of neutrophils and eosinophils induced by antigen was unaltered by prior treatment with capsaicin. In vitro contractile responsiveness to methacholine was not significantly different in bronchial tissues removed from capsaicin- and vehicle-pre-treated rabbits. In addition, there were no significant differences in responses to methacholine in preparations denuded of epithelium. Contraction of bronchial tissue induced by exogenously applied capsaicin in vitro, although modest, was significantly inhibited in capsaicin-pre-treated animals. In vehicle-pre-treated rabbits, contraction induced by a second challenge with capsaicin 45 min later was significantly reduced to a level that made responses not significantly different from those obtained in capsaicin-pre-treated tissues. The results of the present study demonstrate that antigen-induced airway hyperresponsiveness to inhaled histamine in immunised rabbits is inhibited by prior treatment with capsaicin. These findings suggest the involvement of capsaicin-sensitive nerves in antigen-induced airway hyperresponsiveness but not acute bronchospasm or cell infiltration induced by antigen.