Bronchodilator Effect Research Articles

Evaluation of the Bronchodilator Effect of Guaco Syrup: a Randomized, Double-blind, Crossover Clinical Trial

Guaco is an herb used to treat respiratory disorders. It is included in the list of drugs offered by the Brazilian health system, however its efficacy has never been assessed by clinical trials. A randomized, double-blind, crossover clinical trial was conducted to evaluate the bronchodilator activity of guaco syrup (Mikania glomerata Spreng., Asteraceae) compared with salbutamol and placebo in volunteers presenting with bronchoconstriction. Fifteen volunteers were analyzed. Mean changes in expiratory values of each group, as well as the percentage increase to baseline and to the predicted value were compared. Guaco was statistically different from salbutamol (p < 0.001 for all three outcomes), and it was not different from placebo (p values of 0.824, 0.295, and 0.760). No adverse events were reported during trial. A bronchodilator effect resulting from guaco syrup was not observed in this trial. Other clinical trials should be conducted to explore alternative mechanisms of actions of guaco and, hence, support or reject the use of this herb in the treatment of respiratory disorders. Trial registration: RBR-4n26tf

Evaluation of bronchodialatory and antimicrobial activities of Otostegia fruticosa: A multi-mechanistic approach

Otostegia fruticosa, a plant belonging to the family Lamiaceae, is endemic to Ethiopia. In Ethiopian traditional medicine, O. fruticosa has been used for the treatment of several respiratory-related disorders. The present study was designed to evaluate the bronchodilatory and antimicrobial activities of O. fruticosa leaves crude extract (Of.Cr). Ex-vivo experiments were conducted on guinea-pig trachea provided with physiological oxygenated buffer solution using emkaBath setup. The crude extract was analyzed by gas chromatography-mass spectrometry. Of.Cr, showed the presence of terpenes, fragrance components, saponins, and higher fatty acids. Of.Cr when tested on contracted tracheal chains with carbamylcholine (CCh, 1 µM) and high K+ (80 mM) produced relaxation by showing higher potency against CCh with incomplete inhibition of high K+. Dicyclomine, used as a positive control, also showed selectively higher potency to inhibit CCh when compared with its effect against K+. In the anticholinergic curves, Of.Cr at 1 mg/mL deflected CCh-induced concentration–response curves (CRCs) competitively to the right like dicyclomine (0.03 µM) and atropine whereas a higher dose of Of.Cr (3 mg/mL) produced a non-parallel shift in the CCh curves like a higher dose of dicyclomine (0.1 µM). In the calcium channel inhibitory assay, Of.Cr at 3 & 5 mg/mL, deflected CRCs of Ca++ to the right like verapamil, used as positive control. Of.Cr, at concentrations (1–3 mg/mL) increases cAMP levels in isolated tracheal homogenates, similar to positive control phosphodiesterase inhibitor (papaverine). When tested for antibacterial activity against standard and clinical strains, Of.Cr was found more active (MIC 475 µg/ml) against S. aureus (NCTC 6571), while the maximum inhibition (MIC 625 µg/ml) was observed by the extract when tested against MRSA. These results determine the mechanistic pathways of the observed bronchodilatory effect of Otostegia fruticosa with a combination of anticholinergic and dual inhibition of phosphodiesterase and voltage-gated Ca++ channels.

Therapeutic effects of nebulized verapamil on chronic obstructive pulmonary disease: A randomized and double-blind clinical trial.

In this study, we assessed the clinical effect of inhaled verapamil on hospitalized COPD patients in a randomized and double-blind study. COPD patients randomly received 10mg of inhaled verapamil or 4 cc nebulized distilled water (DW) as placebo. Twenty patients enrolled in each group with no difference in baseline characteristics. Mean age was 64.95±8.9 and 66.9±10.74years in verapamil and control group; respectively, (P>0.05). The mean dyspnea score was 6.4±1.2 and 6.2±1.8 in the verapamil and control group, respectively and decreased to 4.9±1.3 and 5.7±1.8 after the intervention. The mean change in the verapamil group was significantly higher, (22.43%±10.6% vs 8.7%±12.1%), P=0.00. Unlike the control group, the FEV1 value in the verapamil group significantly increased and reached to 1.17±0.4L from 1.03±0.4. There was a significant decrease in airway resistance in both groups after intervention. However, neither total lung capacity and residual volume nor forced vital capacity changed significantly. Moreover, oxygen saturation in the verapamil group changed 4.8%±2.5% and this improvement in the control group was 1.8±1 (P=0.00). Smoker subjects, ones with PAP more than 35mmHg and obese patients benefit from verapamil. The beneficial impact of inhaled verapamil on the diminishing of dyspnea score along with its bronchodilatory effect would make this selective calcium blocker agent a therapeutic option in COPD.

Airway smooth muscle adapting in dynamic conditions is refractory to the bronchodilator effect of a deep inspiration.

Airway smooth muscle (ASM) is continuously strained during breathing at tidal volume. Whether this tidal strain influences the magnitude of the bronchodilator response to a deep inspiration (DI) is not clearly defined. The present in vitro study examines the effect of tidal strain on the bronchodilator effect of DIs. ASM strips from sheep tracheas were mounted in organ baths and then subjected to stretches (30% strain), simulating DIs at varying time intervals. In between simulated DIs, the strips were either held at a fixed length (isometric) or oscillated continuously by 6% (length oscillations) to simulate tidal strain. The contractile state of the strips was also controlled by adding either methacholine or isoproterenol to activate or relax ASM, respectively. Although the time-dependent gain in force caused by methacholine was attenuated by length oscillations, part of the acquired force in the oscillating condition was preserved postsimulated DIs, which was not the case in the isometric condition. Consequently, the bronchodilator effect of simulated DIs (i.e., the decline in force postsimulated versus presimulated DIs) was attenuated in oscillating versus isometric conditions. These findings suggest that an ASM operating in a dynamic environment acquired adaptations that make it refractory to the decline in contractility inflicted by a larger strain simulating a DI.

Effects of nebulizer fill volume on the efficacy and safety of the bronchodilator

This study aimed to demonstrate the effect of adding saline to the respirable-solution of salbutamol placed in a nebulization chamber on the clinical status of the ventilated patient.A total of 160 (80 female) asthmatic subjects were randomly divided into 8 groups (gp1-gp8). They received 0.5 ml salbutamol respirable-solution (5000 μg\\ml), 0.5 ml salbutamol respirable-solution+1 ml saline, 0.5 ml salbutamol respirable-solution+2 ml saline, 0.5 ml salbutamol respirable-solution+3 ml saline, 1 ml salbutamol respirable-solution, 1 ml salbutamol respirable-solution+1 ml saline, 1 ml salbutamol respirable-solution+2 ml saline and 1 ml salbutamol respirable-solution+3 ml saline respectively using jet-nebulizer. Forced expiratory volume in 1 s as a percentage of predicted (FEV1%), oxygen-saturation, pulse-rate, and respiratory-rate were measured before and 10–20 min after the nebulization of the salbutamol.0.5 ml salbutamol respirable-solution had no significant improvement in FEV1%. However, 1 ml had a significant improvement in FEV1% (p < 0.001). Increasing fill volume increased the FEV1% significantly (p < 0.001). No significant difference in FEV1% when saline increased from 2 ml to 3 ml. There was no significant difference in oxygen-saturation before and after the administration of salbutamol. Pulse-rate increased significantly (p < 0.01) at higher fill-volumes especially in group 6–8. A few subjects complained of palpitation and headache at the end of nebulization.Increasing fill-volume with jet-nebulizer enhanced the bronchodilator effect of salbutamol and plateau occurs after 2 ml added saline.

The Possible Therapeutic Effects of Some Medicinal Plants for Chronic Cough in Children.

The use of plants or their isolated bioactive components for the prevention and treatment of various disorders has been developed. Here, we aim to identify effective medicinal plants for relief of cough and respiratory symptoms in children. The data of this review article were obtained from published articles in scientific databases, including PubMed, Google Scholar, and Scopus, until December 2019. The keywords, including “Zataria multiflora Boiss.” OR “Portulaca oleracea L.” OR “Ferula assa-foetida L.” OR “Nigella sativa L.” AND “respiratory symptoms” OR “airway inflammation” OR “smooth muscle relaxant effects,” were searched individually or combined. The mentioned medicinal plants decreased total white blood cell (WBC), neutrophils, and eosinophils counts of blood and lung lavage in animal model-induced respiratory disorders. These plants also have protective effects on serum immunoglobulin, antibody titer, eosinophil count, and proinflammatory cytokines. Evidence from the studies indicated that the abovementioned medicinal plants have smooth muscle relaxant properties (bronchodilator effects) via stimulation of β-adrenoceptor or inhibition of muscarinic receptors (in vitro) and also improved the pulmonary function test in clinical settings. These medicinal plants are safe and easy to use. Based on the anti-inflammatory, anti-antispasmodic, and immunomodulatory effects, the clinical benefit may be assumed, therefore considering a place for these medicinal plants in relieve of chronic cough and symptoms of children's allergy, asthma, and common cold.

Soluble Guanylate Cyclase Agonists Induce Bronchodilation in Human Small Airways.

The soluble guanylyl cyclase (sGC)-cyclic guanosine monophosphate signaling pathway evokes vascular smooth muscle relaxation; whether this pathway mediates airway smooth muscle relaxation remains controversial. We posit that sGC activators are equi-effective as β-agonists in reversing contractile agonist-induced airway smooth muscle shortening. To provide clarity, we tested the efficacy of sGC stimulator and activator drugs, BAY 41-2272 and BAY 60-2270, respectively, in reversing bronchoconstriction of human small airways using human precision-cut lung slices (hPCLS). Both BAY drugs reversed carbachol-induced bronchoconstriction to a maximal degree comparable to that of formoterol. Moreover, the sGC drugs remained effective bronchodilators despite formoterol-induced desensitization of the airways. Analysis of the hPCLS after their activation by sGC or β2-adrenergic receptor agonist showed distinct cyclic nucleotide accumulation in the hPCLS. Collectively, these data suggest that cAMP and cyclic guanosine monophosphate pathways are equi-effective for reversing carbachol-induced bronchoconstriction in the human airway via separate and distinct second messenger pathways. This should open the door for future studies to test whether sGC-targeted drugs alone or in combination can serve as effective bronchodilators in asthma and chronic obstructive pulmonary disease.

Effects of β2-adrenergic agonists on house dust mite-induced adhesion, superoxide anion generation, and degranulation of human eosinophils.

BackgroundEven in subjects who are not sensitized to house dust mite (HDM), allergic symptoms can be clinically aggravated by exposure to dust. We previously reported that Dermatophagoides farinae (Df), an important HDM, or Der f 1, a major allergen of Df, induced the effector functions of eosinophils, which may be an important mechanism for HDM-induced symptoms in nonsensitized patients. In a clinical setting, β2-adrenergic agonists, such as salbutamol and formoterol, are used for the treatment of asthma attacks or exacerbation to release the airway obstruction. Several reports have suggested that some β2-adrenergic agonists have an anti-inflammatory capacity.ObjectiveIn this study, we investigated whether β2-adrenergic agonist could modify the Df- or Der f 1-induced activation of eosinophils.MethodsBlood eosinophils obtained from healthy donors were preincubated with either formoterol (1 μM), salbutamol (1 μM), or buffer control and then stimulated with Df extract (1 μg/mL) or Der f 1 (100 pg/mL). Eosinophil adhesion to intercellular adhesion molecule (ICAM)-1 was measured using eosinophil peroxidase assays. Generation of superoxide anion (O2−) was examined based on the superoxide dismutase-inhibitable reduction of cytochrome C. Eosinophil-derived neurotoxin (EDN) concentrations in cell media were measured by enzyme-linked immunosorbent assay.ResultsFormoterol, but not salbutamol, suppressed the Df- or Der f 1-induced eosinophil adhesion to ICAM-1. Furthermore, formoterol, but not salbutamol, suppressed Df-induced O2− generation or EDN release. Neither formoterol nor salbutamol suppressed spontaneous eosinophil adhesion, O2− generation, or EDN release.ConclusionThese findings suggested that formoterol, but not salbutamol, suppressed Df- or Der f 1-induced eosinophil activation when used at the same concentration. Therefore, formoterol could potentially be used for the treatment of bronchial asthma via both bronchodilation and anti-inflammatory effect.

Glucagon-Like Peptide 1 and Atrial Natriuretic Peptide in a Female Mouse Model of Obstructive Pulmonary Disease.

Glucagon-like peptide-1 (GLP-1) is protective in lung disease models but the underlying mechanisms remain elusive. Because the hormone atrial natriuretic peptide (ANP) also has beneficial effects in lung disease, we hypothesized that GLP-1 effects may be mediated by ANP expression. To study this putative link, we used a mouse model of chronic obstructive pulmonary disease (COPD) and assessed lung function by unrestrained whole-body plethysmography. In 1 study, we investigated the role of endogenous GLP-1 by genetic GLP-1 receptor (GLP-1R) knockout (KO) and pharmaceutical blockade of the GLP-1R with the antagonist exendin-9 to -39 (EX-9). In another study the effects of exogenous GLP-1 were assessed. Lastly, we investigated the bronchodilatory properties of ANP and a GLP-1R agonist on isolated bronchial sections from healthy and COPD mice.Lung function did not differ between mice receiving phosphate-buffered saline (PBS) and EX-9 or between GLP-1R KO mice and their wild-type littermates. The COPD mice receiving GLP-1R agonist improved pulmonary function (P < .01) with less inflammation, but no less emphysema compared to PBS-treated mice. Compared with the PBS-treated mice, treatment with GLP-1 agonist increased ANP (nppa) gene expression by 10-fold (P < .01) and decreased endothelin-1 (P < .01), a peptide associated with bronchoconstriction. ANP had moderate bronchodilatory effects in isolated bronchial sections and GLP-1R agonist also showed bronchodilatory properties but less than ANP. Responses to both peptides were significantly increased in COPD mice (P < .05, P < .01).Taken together, our study suggests a link between GLP-1 and ANP in COPD.

Revefenacin: A Once-Daily, Long-Acting Bronchodilator For Nebulized Treatment Of COPD.

Bronchodilation with muscarinic antagonists, β2-agonists, and inhaled corticosteroids remains the foundation of pharmaceutical treatment for patients with stable COPD. These drugs are delivered from a variety of devices, including dry powder inhalers, pressurized metered-dose inhalers, soft-mist inhalers, or nebulizers. Nebulized delivery is often preferable in patients who are elderly, are cognitively impaired, are unable to generate sufficient inspiratory force to use their inhaler, have difficulty coordinating hand-breath activity, are too dyspneic to hold their breath for a sufficient time, and/or may be acutely ill. Revefenacin, a once-daily long-acting muscarinic antagonist for nebulization recently approved by the US FDA for the treatment of patients with COPD, was discovered and developed using “duration and lung selectivity-by-design.” This strategy selected a molecule with a high lung-selective index to maximize bronchodilation and limit systemic anti-muscarinic side effects. In early-phase clinical studies, revefenacin for nebulization led to a rapid onset of bronchodilation that was sustained for 24 hrs in patients with moderate to severe COPD. Revefenacin also demonstrated minimal systemic exposure and good tolerability in these studies. Statistically and clinically significant improvements in lung function (ie, peak and/or trough FEV1) relative to placebo were observed with revefenacin in Phase III clinical trials of up to 3 months in patients with moderate to very severe COPD. Revefenacin was well tolerated in Phase III clinical trials with a low incidence of systemic antimuscarinic adverse events, which is consistent with its lung-selective design. There was no evidence of an increased risk of major cardiovascular events. Patient-reported outcome data from clinical trials indicated statistically significant improvements in several disease-specific measures. Revefenacin 175 μg for nebulization provides an effective once-daily treatment option for patients with moderate to very severe COPD who require or prefer nebulized therapy.

Effect of Bronchodilator and Steroid Use on Heart Disease and Stroke Risks in a Bronchiectasis-Chronic Obstructive Pulmonary Disease Overlap Cohort: A Propensity Score Matching Study.

Background: To determine the effects of bronchodilator, steroid, and anti-arrhythmia drug use on the risk of heart disease/stroke (HDS) in patients with bronchiectasis–chronic obstructive pulmonary disease overlap syndrome (BCOS). Methods: We retrospectively enrolled patients with BCOS (BCOS cohort, n = 1,493) and patients without bronchiectasis and chronic obstructive pulmonary disease (COPD) (non-BCOS cohort, n = 5,972). The cumulative incidence of HDS was analyzed through Cox proportional regression. We calculated adjusted hazard ratios (aHRs) and their 95% confidence intervals (CIs) for HDS after adjustments for sex, age, comorbidities, long-acting β2-agonist or long-acting muscarinic antagonist (LABAs/LAMAs) use, short-acting β2-agonist or short-acting muscarinic antagonist (SABAs/SAMAs) use, oral steroid (OSs) or inhaled corticosteroid steroid (ICSs) use, and anti-arrhythmia drugs use. Results: The aHR (95% CI) for HDS was 1.08 (0.28–4.06) for patients using LAMAs compared with those not using drugs. Regarding drug use days, the aHRs (95% CIs) were 32.2 (1.79–773.0), 1.85 (1.01–3.39), and 31.1 (3.25–297.80) for those with recent SABAs use, past ICSs use, and past anti-arrythmia drugs use, respectively. Regarding cumulative drug dose, the aHRs (95% CIs) were 2.12 (1.46–3.10), 3.48 (1.13–10.6), 3.19 (2.04–4.99), 28.1 (1.42–555.7), 2.09 (1.32–3.29), 2.28 (1.53–3.40), and 1.93 (1.36–2.74) for those with a low dose of SABAs, medium dose of SABAs, low dose of SAMAs, low dose of ICSs, medium dose of ICSs, low dose of OSs, and medium dose of OSs, respectively. Conclusions: Compared with patients without bronchiectasis and COPD, BCOS patients with recent SABAs, past ICSs, and past anti-arrhythmia drugs use; a low or medium SABAs ICSs, and OSs dose; and a low SAMAs dose had a higher risk of HDS. LAMAs were not associated with HDS.

Development and Validation of Salbutamol, Bromhexine, Ambroxol and Guauaifenesin Determination in Human Plasma by HPLC-MS/MS Method

Introduction. Multicomponent oral drugs containing salbutamol, bromhexine, ambroxol and guaifenesin have a mucolytic, expectorant and bronchodilator effect. The development method for determination substances in biological fluids is a main procedure for performing the analytical part of pharmacokinetic studies and bioequivalence studies of multicomponent drugs. There is no published data of the determination of bromhexine, ambroxol and guaifenesin, but there a lot of published methods for divided determination analytes in a biological fluid. This study presents the development and validation of a method of the determination of salbutamol, bromhexine, ambroxol and guaifenesin in human blood plasma by high performance liquid chromatography with tandem mass spectrometric detection. A sample preparation was perfomed by solid-phase extraction. Deuterated derivatives were used as internal standards.Aim. The aim of the study is to develop a method for the quantitative determination of salbutamol, bromhexine, ambroxol and guaifenesin in human plasma by HPLC with tandem mass spectrometric detection for performing the analytical part of pharmacokinetic studies.Materials and methods. Determination of salbutamol, bromhexine, ambroxol and guaifenesin in human plasma by HPLC with tandem mass spectrometric detection. A sample was prepared using solid-phase extraction.Results and discussion. The method was validated by next validation parameters: selectivity, matrix effect, calibration curve, accuracy, precision, limit of quantification, carry-over and stability.Conclusion. The method of the determination of salbutamol, bromhexine, ambroxol and guaifenesin in human plasma was developed and validated by HPLC-MS/MS. The analytical range of the was 0.1–20 ng/mL in plasma for salbutamol, 0.25–25 ng/mL in plasma for bromhexine, 0.075–3 ng/mL in plasma for ambroxol, and 10–2000 ng/mL in plasma for guaifenesin. Method could be applied to determination of salbutamol, bromhexine, ambroxol and guaifenesin in plasma for PK and BE studies.

Effects of 1,8-cineole (eucalyptol) on the activity of human bronchial tissue

1,8-cineole (eucalyptol) is used for the treatment of bronchial complaints, sinusitis and colds. Experiments have previously shown that 1,8-cineole, a monoterpene (C-10), has a very pronounced spasmolytic effect on smooth muscle fibre. In nearly all clinical applications with 1,8-cineole, especially when used in conjunction with allergic symptoms, histamine receptors prove to be crucial for treatment (use of histamine inhibitors). Results: The desired 1,8-cineole effects are attained through: specifically blocking H1 histamine receptors, without influencing ACh receptors Inhibiting the contractile activity of human bronchial smooth muscle by activating H2 histamine receptors. The ultimate goal of this study was to address the bronchodilatory effect of this compound, using human airway smooth muscle in order to demonstrate a possible role for 1,8-cineole in airway diseases. Keywords: Smooth muscle fibre; 1,8-cineole (eucalyptol); Human bronchial tissue; Bronchitis; Monoterpene

Relaxing effects of clenbuterol, ritodrine, salbutamol and fenoterol on the contractions of horse isolated bronchi induced by different stimuli

β2-adrenoceptor agonists are considered the most effective drugs to counteract bronchoconstriction in horses with asthma, but only clenbuterol is commonly employed in clinical practice. We evaluated the effects of different selective β2 agonists: clenbuterol, ritodrine, salbutamol, and fenoterol on the contractions of isolated bronchial muscle of horses induced by electrical field stimulation (EFS), carbachol, histamine, and KCl. All β2 agonists reduced the amplitude of contraction induced by the different stimuli but with variable efficacy and potency. Fenoterol and salbutamol were more effective than clenbuterol in relaxing the bronchial contractions induced by EFS and histamine, and were able to completely abolish carbachol-induced contractions, unlike clenbuterol and ritodrine. The respective potency values (pEC50) of clenbuterol, ritodrine, salbutamol, and fenoterol were 7.74 ± 0.20, 7.77 ± 0.17, 7.30 ± 0.23, 8.01 ± 0.13, for EFS-induced contractions; 8.39 ± 0.26, 5.49 ± 0.28, 6.63 ± 0.14, 7.68 ± 0.11, for carbachol-induced contraction; 7.39 ± 0.27, 7.04 ± 0.28, 6.45 ± 0.34, 7.34 ± 0.22, for histamine-induced contraction; 7.15 ± 0.06, 6.07 ± 0.20, 6.48 ± 0.14, 6.70 ± 0.18, for KCl-induced contraction. Salbutamol and fenoterol showed a higher efficacy than clenbuterol in relaxing horse bronchial muscle pre-contracted by most stimuli. Clenbuterol displayed a good potency but a rather low efficacy, and this may be due to its partial agonist nature; ritodrine showed lower or not significantly different efficacy and potency compared to the other agonists. An evaluation of the clinical efficacy by fenoterol and salbutamol in horses with asthma could be of great interest to assess if they could represent more effective bronchodilators compared to clenbuterol.

Synthesis, Purification, and Selective β2-AR Agonist and Bronchodilatory Effects of Catecholic Tetrahydroisoquinolines from Portulaca oleracea

A green, biomimetic, phosphate-mediated Pictet-Spengler reaction was used in the synthesis of three catecholic tetrahydroisoquinolines, 1, 2, and 12, present in the medicinal plant Portulaca oleracea, as well as their analogues 3-11, 13, and 14, with dopamine hydrochloride and aldehydes as the substrates. AB-8 macroporous resin column chromatography was applied for purification of the products from the one-step high-efficacy synthesis. It eliminated the difficulties in the isolation of catecholic tetrahydroisoquinolines from the aqueous reaction system and unreacted dopamine hydrochloride. Activity screening in CHO-K1/Gα15 cell models consistently expressing α1B-, β1-, or β2-adrenergic receptors indicated that 12 and 2, compounds that are present in P. oleracea, possessed the most potent β2-adrenergic receptor agonist activity and 2 was a selective β2-adrenergic receptor agonist at the concentration of 100 μM. Both 12 and 2 exhibited dose-dependent bronchodilator effects on the histamine-induced contraction of isolated guinea-pig tracheal smooth muscle, with EC50 values of 0.8 and 2.8 μM, respectively. These findings explain the scientific rationale of P. oleracea use as an antiasthmatic herb in folk medicine and provide the basis for the discovery of novel antiasthma drugs.

Chinese star anise and anise, magic herbs in traditional Chinese medicine and modern pharmaceutical science

Star anise (Illicium verum Hook. f.) is an important herb in traditional Chinese medicine as well as traditional Asian medicine. The fruit is aromatic and has a strong, pungent and mildly sweet taste. Star anise is one of the many species that contain bioactive compounds as well as a number of phenolic and flavonoid compounds, having antioxidant, preservative and antimicrobial properties. All relevant papers in the English language from researchers of different countries were collected. The keywords of Chinese star anise, anise, traditional Chinese medicine and modern pharmaceutical science were searched in Google Scholar, Scopus, Research Gate and PubMed. Its seeds are good source of minerals like calcium, iron, copper, potassium, manganese, zinc, and magnesium. The essential oil of Chinese star anise contains anethole which has shown several functional properties including antimicrobial, antioxidant, hypoglycemic, hypolipidemic and oestrogenic properties. Due to all positive characteristics, such as antidiabetic, hypolipidemic, antioxidant activities, anticancer and antimicrobial properties, both seeds and essential oils of anise is promising for safe use as super food supplements and raw constituents in the both pharmaceutical and food industries. Anise seed oil contains anethol, estragole, eugenol, pseudisoeugenol, methyl chavicol and anisaldehyde, coumarins, scopoleting, umbelliferon, estrols, terpene hydrocarbons, and polyacetylenes as the major compounds. The plant oil has both pharmacological and clinical effects. The pharmacological effects consist of antimicrobial, hepatopreotective, anticonvulsant, anti-inflammatory, antispasmodic, bronchodilator, estrogenic, expectorant and insecticidal effects, and clinical effects such as nausea, constipation, menopausal period, virus, diabetes, obesity and sedative action. Combined with a nutritious diet, other traditional Chinese and Asian medicine, Chinese star anise and ansie seed may improve various aspects of health. More clinical studies are necessary to uncover the numerous substances and their effects in ginseng that contribute to public health.&#x0D; Asian J. Med. Biol. Res. June 2019, 5(3): 162-179

Current state and future prospect of the therapeutic strategy targeting cysteinyl leukotriene metabolism in asthma.

Asthma is an allergic disorder with dominant type 2 airway inflammation, and its prevalence is increasing worldwide. Inhalation of corticosteroids is the primary treatment for asthma along with add-on drugs, including long-acting β2 agonists and/or cysteinyl leukotriene (cys-LT) receptor antagonists, in patients with poorly controlled asthma. Cys-LTs are composed of leukotriene C4 (LTC4), LTD4, and LTE4, which are enzymatically metabolized from arachidonic acid. These molecules act as inflammatory mediators through different types of high-affinity receptors, namely, CysLT1, CysLT2, and CysLT3 (also named as GPR99). CysLT1 antagonists possessing anti-inflammatory and bronchodilatory effects can be orally administered to patients with asthma. Recently, molecular biology-based studies have revealed the mechanism of inflammatory responses via other receptors, such as CysLT2 and CysLT3, as well as the importance of upstream inflammatory regulators, including type 2 cytokines (e.g., interleukins 4 and 5), in controlling cys-LT metabolism. These findings indicate the therapeutic potential of pharmacological agents targeting cys-LT metabolism-related receptors and enzymes, and antibody drugs neutralizing or antagonizing type 2 cytokines. This review focuses on the current state and future prospect of the therapeutic strategy targeting cys-LT metabolism.

Shortening of airway smooth muscle is modulated by prolonging the time without simulated deep inspirations in ovine tracheal strips.

The shortening of airway smooth muscle (ASM) is greatly affected by time. This is because stimuli affecting ASM shortening, such as bronchoactive molecules or the strain inflicted by breathing maneuvers, not only alter quick biochemical processes regulating contraction but also slower processes that allow ASM to adapt to an ever-changing length. Little attention has been given to the effect of time on ASM shortening. The present study investigates the effect of changing the time interval between simulated deep inspirations (DIs) on ASM shortening and its responsiveness to simulated DIs. Excised tracheal strips from sheep were mounted in organ baths and either activated with methacholine or relaxed with isoproterenol. They were then subjected to simulated DIs by imposing swings in distending stress, emulating a transmural pressure from 5 to 30 cmH2O. The simulated DIs were intercalated by 2, 5, 10, or 30 min. In between simulated DIs, the distending stress was either fixed or oscillating to simulate tidal breathing. The results show that although shortening was increased by prolonging the interval between simulated DIs, the bronchodilator effect of simulated DIs (i.e., the elongation of the strip post- vs. pre-DI) was not affected, and the rate of re-shortening post-simulated DIs was decreased. As the frequency with which DIs are taken increases upon bronchoconstriction, our results may be relevant to typical alterations observed in asthma, such as an increased rate of re-narrowing post-DI.NEW & NOTEWORTHY The frequency with which patients with asthma take deep inspirations (DIs) increases during bronchoconstriction. This in vitro study investigated the effect of changing the time interval between simulated DIs on airway smooth muscle shortening. The results demonstrated that decreasing the interval between simulated DIs not only decreases shortening, which may be protective against excessive airway narrowing, but also increases the rate of re-shortening post-simulated DIs, which may contribute to the increased rate of re-narrowing post-DI observed in asthma.

El tratamiento broncodilatador en la prevención de las exacerbaciones de la EPOC

The natural course of chronic obstructive pulmonary disease usually includes exacerbations. chronic obstructive pulmonary disease patients suffer from 1-4 exacerbations per year on average. These are associated with worsening quality of life and increased mortality. Reducing and controlling the number of exacerbations is one of the main goals of chronic obstructive pulmonary disease treatment. Among current treatments, tiotropium is the active substance with the strongest evidence in the reduction of moderate/severe exacerbations, together with a good safety and tolerability profile. The addition of olodaterol to tiotropium offers well-tolerated and effective double bronchodilation for improving lung function, quality of life, and decreased dyspnoea compared to its single components. This also reduces the annual rate of moderate/severe exacerbations vs. tiotropium by 7%, although not reaching the pre-specified statistical significance level of P<.01.

Bronchodilator effect of apigenin and luteolin, two components of Dracocephalum kotschyi on isolated rabbit trachea

Introduction: Dracocephalum kotschyi is a native Iranian plant with antispasmodic activities on smooth muscles such as ileum and uterus. However, so far antispasmodic effect of D. kotschyi on tracheal smooth muscle has not been reported. Therefore, the objective of this research was to investigate antispasmodic activity of D. kotschyi extract and two of its components luteolin and apigenin on rabbit tracheal contraction in vitro. Methods: Rabbits were euthanized by carbon dioxide and the trachea was dissected and immersed in a Tyrode’s solution. Tracheal rings were prepared and mounted vertically in an organ bath at 37°C and gassed continuously with O2. The tracheal ring preparations were contracted with acetylcholine (ACh) and KCl. The isotonic tension was recorded before and after addition of aminophylline, apigenin, luteolin or flavonoids rich extract of D. kotschyi. Flavonoids rich extract were prepared from D. kotschyi using solvent-solvent fractionation technique. Results: Standard drug aminophylline, prevented tracheal ring preparation contracted with ACh. Cumulative addition of aminophylline also attenuated tonic contraction induced by KCl on tracheal smooth muscle. D. kotschyi extract at concentration ranges of 32-512 μg/mL in a concentration dependent manner inhibited KCl and ACh induced tracheal contraction. Apigenin and luteolin (range 16–512 μg/mL) relaxed KCl and ACh-induced contraction of tracheal smooth muscle in vitro in a concentration-dependent manner. Conclusion: This study demonstrated that D. kotschyi extract is a relaxant of tracheal smooth muscle. The relaxant effect of D. kotschyi extract could be due to its flavonoids component such as apigenin and luteolin.