Asthma Disorders Research Articles

Multicomponent qualitative and quantitative analysis of Farfarae Flos in serum using UHPLC-Q TOF-MS

Farfarae Flos is a traditional herb widely employed for treating coughs, bronchitis, and asthmatic disorders. In the current study, we utilized SWATH and IDA data acquisition modes in combination with multiple data processing techniques to identify Farfarae Flos metabolites in mice serum. A total of 56 compounds were characterized, including 31 phenolic acids, 13 flavonoids, 11 sesquiterpenoids and 1 alkaloid. Further quantitative analysis was conducted on 12 absorbed metabolites, utilizing a newly developed and rigorously validated analytical method. Our approach demonstrated an acceptable level of specificity, accuracy, precision, and stability. When applied to compare the serum of mice treated with FF, all 12 metabolites showed the highest concentration at 0.5 h. Overall, this study presented a novel strategy for unraveling the active compounds of FF via serum pharmacochemistry analysis, which made a foundation for exploring the pharmacodynamic material basis of FF.

Evaluation of the Pharmacological Potential of Nyctanthes Arbor-Tristis Flowers Extract against Milk Induced Asthmatic Disorder in Swiss Albino Mice

Evaluation of the Pharmacological Potential of Nyctanthes Arbor-Tristis Flowers Extract against Milk Induced Asthmatic Disorder in Swiss Albino Mice

COVID-19: A Threat for Survival of Obese People-A Review Paper

Abstract: Obesity is a condition that increases the possibility of developing a wide range of non-communicable diseases and as a serious consequence, also promotes the chances of being suffered by deadly infectious diseases. This is most clearly noticeable in the pandemic situation of global spread of the COVID-19. Obesity is considered as an access to various non-communicable diseases as well as mental-health illness and in present scenario it has been found to be a key factor in COVID-19 complications and mortality. Further, obesity has been identified as a major comorbity in patients with asthmatic disorders which also proves it as a risk factor for more serious corona virus disease. Obesity has been recognized as a disease in its own right as well as a risk factor for other health issues including significantly worsening the outcomes of COVID-19 infection. Keywords: Obesity, COVID-19, Pandemic, Comorbity.

Novel graphene-nanoclay hybrid electrodes for electrochemical determination of theophylline

Electro-analytical methods are interested in the interaction of electricity and chemistry, calculating quantities of electricity mainly current, potential, charges and their association with chemical properties. This usage for scientific purposes of electrical measurements has found a wide variety of uses, particularly in industrial quality management, environmental pollutionmanagement, and biomedical research. Theophylline (THP) is one of the phosphodiesterase inhibiting drugs used in the treatment of asthmatic disorders. High dosage implements some adverse effect on the health. Thus, in the present study, we have prepared the electrode by drop casting graphene oxide – nanoclay matrix on the glassy carbon electrode surface (GO-NC/GCE), for the quantification of THP. The electrochemical study of THP was done by using cyclic voltammetry and square wave voltammetry techniques. Voltammograms reveals that, higher electro-oxidation peak current of THP at modified electrode suggesting the effective modification of the electrode. From the pH study, it’s found that the THP has undergone an oxidation mechanism involving the same number of electrons and protons. The sweep rate effect revealed that two number of electrons were involved in the diffusion controlled electrode mechanism. A wide range of linearity was found for GO-NC/GCE, 3.0 × 10−8–5.0 × 10−4 M with LOD value 3.12 × 10−9 M. Excipients and Metal ion interference study shows the selectivity and analysis of THP in pharmaceutical drug and spiked urine samples gives the real time applications of modified electrode. We have discovered that the modified electrode shows remarkable detection and good recovery value.

Uncovering the anticancer mechanism of petroleum extracts of Farfarae Flos against Lewis lung cancer by metabolomics and network pharmacology analysis.

Lung cancer shows the highest incidence rate in the world. Thus, it has become increasingly important to find therapeutic drugs to treat lung cancer. Farfarae Flos (FF) has been used in traditional Chinese medicine to treat pulmonary diseases such as cough, bronchitis and asthmatic disorders. In this study, the anti-proliferation effects of petroleum extracts of FF (PEFF) on Lewis lung cancer cells and the corresponding mechanisms were studied using cell metabolomics. Fifteen differential metabolites in the cell extracts and the corresponding medium related to the anti-proliferation effect of PEFF were identified, which were probably involved in pyruvate metabolism and glycine, serine and threonine metabolism. For the cellular uptake compounds in PEFF, six metabolites derived from two prototype compounds were also tentatively identified by UHPLC-Q-Orbitrap high-resolution MS. Network pharmacology analysis demonstrated that the anti-proliferation mechanism of PEFF was also probably related to the target genes, including, Aurora-A, glutathione S-transferase Mu 1 (GSTM1), glutathione S-transferase P 1 (GSTP1), progesterone receptor and heme oxygenase-1 (HO-1), and further associated with the proteoglycans and PI3K/Akt signaling pathway. Cell metabolomics and network pharmacology analysis provided a holistic method to investigate the anti-proliferation mechanisms of PEFF. However, further studies were still needed to validate the potential target genes, pathways and active compounds in PEFF.

Anti‐inflammatory Effect of Hydrolyzed Jujube Ethanolic Extract

Air pollutants, commonly derived from combustion reaction, are correlated with systematic inflammation, causing bronchial and asthmatic disorders. Therefore, it is very important to develop the ingredients which protect people from pulmonary damage caused by air pollutants. This study aimed at examining the anti‐inflammatory activity of Zizyphus jujube extract. Jujube fruit harvested from Gyeongsan region, Republic of Korea was ground, heated, and extracted in aqueous ethanol with or without enzymatic hydrolysis using Viscozyme® L (Novozyme, Bagsvaerd, Denmark). The jujube ethanolic extract prepared after treatment with heat and the enzyme (HJE) was found to effectively scavenge radicals as well as contain the considerable levels of total phenolics and flavonoids compared to non‐hydrolyzed extract (NHJE). In vitro studies using various types of cell lines demonstrated that HJE (1) decreased nitric oxide (NO) production from lipopolysaccharide (LPS)‐treated Raw 264.7 murine macrophages in a concentration‐dependent manner, (2) lowered secretions of pro‐inflammatory cytokines including tumor necrosis factor α (TNFα), interleukin‐6 (IL‐6) and interleukin‐1β (IL‐1β) from O‐tetradecanoylphorbol‐13‐acetate (TPA)‐treated THP‐1 human monocytes, and (3) reduced expressions of inflammation‐associated proteins, such as cytoplasmic COX‐2, iNOS, and nuclear NF‐κB in A549 human lung epithelial cells. To further examine the anti‐inflammatory effect of dietary HJE in animal, C57BL/6J mice were orally fed HJE for 2 weeks, followed by induction of lung inflammation by i.p. administration of benzo(a)pyrene (50 mg/kg B.W). A total of forty eight C57BL/6J mice (6‐week old male, 20–25 g) were divided into 6 groups (n = 8) as follows: (1) control, (2) B(a)P alone, (3) B(a)P+NHJE‐L (0.75 g/Kg B.W), (4) B(a)P+NHJE‐H (1.5 g/Kg B.W), (5) B(a)P+HJE‐L (0.75 g/Kg B.W), and (6) B(a)P+HJE‐H (1.5 g/kg B.W). Oral supplementation of HJE notably diminished the B(a)P‐induced elevation of pro‐inflammatory cytokine levels in the plasma and attenuated B(a)P‐induced pulmonary inflammation as evaluated by histological observation. These findings suggest that HJE can protect the lung epithelial cells from B(a)P‐induced injury presumably through attenuating macrophage‐associated inflammatory response and could be developed into the agent that suppresses air pollutant‐induced lung inflammation.Support or Funding InformationThis study was funded by the Forest Resources Development Institute of Gyeongsangbuk‐do, and the National Research Foundation of Korea grant (Grant No. 2017R1A2B4005087) by the Ministry of Science and ICT, Republic of Korea.

Airway inflammation and remodeling of cigarette smoking exposure ovalbumin-induced asthma is alleviated by CpG oligodeoxynucleotides via affecting dendritic cell-mediated Th17 polarization

Cigarette smoking (CS) is common in asthma, aggravating inflammatory reactions. However, the current treatment strategies for asthma are still not effective enough, and novel therapeutic approaches are required for CS-induced asthmatic disorders. We here investigated the ability of CpG oligodeoxynucleotides (CpG-ODNs) to inhibit airway inflammation and remodeling in ovalbumin (OVA)-associated asthma in mice exposed to chronic CS, revealing potential mechanistic insights. Lung tissue specimens were histologically analyzed. Th1/Th2/Th17 associated cytokines in serum, bronchoalveolar lavage fluid (BALF), and lung specimens were quantitated by ELISA, qRT-PCR and immunoblot. Parameters of bone marrow-derived dendritic cells (BMDCs) functions were evaluated as well. The results showed that BALB/c mice after CS and OVA treatments developed an asthmatic phenotype with airway inflammation involving both eosinophils and neutrophils, goblet cell metaplasia, airway remodeling, and elevated OVA-specific serum IgE, serum IL-17A, and BALF Th17/Th2 associated cytokines. CpG-ODNs and budesonide were found to synergistically inhibit inflammatory cell recruitment in the lung, airway remodeling, IgE synthesis, and Th17/Th2 associated cytokines. Mechanistically, CpG-ODNs and budesonide acted synergistically on BMDCs via downregulation of TSLP receptor (TSLPR) and IL-23 production, and subsequently contributed to dampen Th17/Th2 polarization in CS-associated asthma. In conclusion, combined administration of CpG-ODNs and budesonide, in a synergistic manner, inhibits airway inflammation, and tissue remodeling mediated by BMDCs by regulating IL-23 secretion and blocking TSLP signaling, which subsequently contribute to alleviate Th17/Th2 imbalance in CS-associated asthma.

Is There An Explanation for How An Irritant Causes A Nonallergic Asthmatic Disorder Such as Reactive Airways Dysfunction Syndrome (RADS)?

Is There An Explanation for How An Irritant Causes A Nonallergic Asthmatic Disorder Such as Reactive Airways Dysfunction Syndrome (RADS)?

An overview on nanoparticle based approach for treatment and management of asthmatic disorder

An overview on nanoparticle based approach for treatment and management of asthmatic disorder

NMR based metabolomic comparison of the antitussive and expectorant effect of Farfarae Flos collected at different stages

Farfarae Flos (FF) is widely used for the treatment of cough, bronchitis, and asthmatic disorders in the Traditional Chinese Medicine (TCM). According to the experience of TCM, only the flower bud can be used as herbal drug, and its medicinal quality becomes lower after blooming. However, the underlying scientific basis for this phenomenon is not fully understood. In this study, the chemical components and the bioactivities of the FF collected at three different development stages were compared systematically. NMR based fingerprint coupled with multivariate analysis showed that the flower buds differed greatly from the fully opened flower both on the secondary and primary metabolites, and the animal experiments showed that the fully opened flower exhibited no antitussive or expectorant effect. In addition, the endogenous metabolites correlated with the antitussive and expectorant effect of FF were also identified. These findings are useful for understanding the rationality of the traditional use of FF, and also suggested the components responsible for the antitussive and expectorant effect of FF.

Comparative metabolism of tussilagone in rat and human liver microsomes using ultra‐high‐performance liquid chromatography coupled with high‐resolution LTQ‐Orbitrap mass spectrometry

Tussilagone is a major component in Tussilago farfara that has been widely used as an anti-tussive herbal medicine for the treatment of bronchitis, cough and asthmatic disorders in the clinic. However, its metabolism has been poorly investigated. In order to clarify its in vitro metabolism, a comparative analysis of its metabolic profile in rat liver microsomes (RLMs) and human liver microsomes (HLMs) was carried out. Further, the cytochrome P450 isoforms (CYPs) involved in the metabolism were investigated. In this work, the biotransformation of tussilagone in RLMs and HLMs was compared using ultra-high-performance liquid chromatography coupled with high-resolution LTQ-Orbitrap mass spectrometry (UHPLC/HRMS) and the CYPs involved in the metabolism were further investigated by recombinant human CYP enzymes. Totally, nine metabolites of tussilagone were identified in RLMs and HLMs based on the proposed MS/MS fragmentation pathways of tussilagone and the accurate MS/MS spectra. Among them, one metabolite (M9) was detected in both RLMs and HLMs while the other eight metabolites were only detected in HLMs. Three hydroxylation metabolites (M6, M7 and M8) were detected in the assay with individual recombinant P450s incubation. M6 was detected in all CYPs except CYP2A6 while M7 and M8 were only observed in CYP3A4. The HR-ESI-MS/MS fragmentation behavior of tussilagone and its metabolic profile in RLMs and HLMs were investigated for the first time. The results demonstrated that the biotransformation of tussilagone involved hydrolysis of ester bonds at C-14 and hydroxylation in the side chains at C-12, C-5' or C-6'. Among the CYPs, CYP3A4 played an important role in the hydroxylation reaction of tussilagone in vitro. Furthermore, the results indicated a species-related difference in the metabolism of tussilagone between RLMs and HLMs. This work provided basic information for the metabolism of tussilagone in RLMs and HLMs, which would help to better understand the pharmacological activities of tussilagone.

Maternal propensity for infections and risk of childhood asthma: a registry-based cohort study

Maternal use of antibiotics during pregnancy has been associated with the development of asthmatic disorders in the offspring. The human microbiome has been suggested to act as an intermediary in this process. To provide clarification on this theory, we studied the temporal relation between maternal use of antibiotics and the risk of childhood asthma. According to national registries, during the observation period (1997-2010), 910,301 children were born in Denmark and were included in the analysis. From these registries, data for cases of childhood asthma were obtained based on hospital admissions, outpatient attendance at a hospital, or use of inhaled corticosteroids. The effect of timing of maternal antibiotic use on the risk of asthma in the offspring was studied by analysis of maternal antibiotic use in the 80 weeks before pregnancy, during pregnancy, and the 80 weeks after pregnancy. Results were adjusted for age and calendar year, birthweight, gestational age, sex, mode of delivery, parity, multiple births, season of birth, and several maternal factors (age, smoking during pregnancy, employment status, and asthma). In this study, we replicated our previous finding that maternal use of antibiotics in pregnancy was associated with an increased risk of childhood asthma: the adjusted incidence rate ratio (aIRR) was 1·24 (95% CI 1·18-1·30) for inpatient admission, 1·22 (1·18-1·26) for outpatient attendance, and 1·18 (1·15-1·20) for inhaled corticosteroid use. A similar and independent association was also recorded for maternal antibiotic use in the 80 weeks before and after the pregnancy. A dose-related association occurred between the risk of childhood asthma and the number of maternal antibiotic treatments and was recorded separately for antibiotic treatment for respiratory tract infections and for other types of infections. Maternal use of antibiotics has a dose-related association with the risk of asthma in the offspring, but this association is independent of the temporal relationship with the pregnancy period. This finding suggests that maternal antibiotic use is a surrogate marker of a mother's general propensity for infections as the underlying link between a mother's use of antibiotics and risk of asthma in the offspring. The Danish Council for Strategic Research, The Lundbeck Foundation, The Pharmacy Foundation of 1991, the Danish Medical Research Council, and National Finance Act.

Phenolics in the Tussilago farfara leaves

Summary Coltsfoot leaves (Farfarae folium) are used in the European medicine in respiratory tract diseases, for cough, bronchitis and asthmatic disorders, while in the traditional Chinese medicine only flower buds (Farfarae flos) have been recognized as a medicine. A short literature review shows that most data concern the chemical composition of the coltsfoot flowers. During the carried out studies we have isolated and identified (UV, 1H and 13C NMR, analysis of acid and enzymatic hydrolyze products) six known flavonols from the coltsfoot leaves: kaempferol and its 3-O-β-glucopyranoside and 3-O-α-rhamnopyranosyl(1→6)- β-glucopyranoside, along with quercetin derivatives: 3-O-β-arabinopyranoside, 3-O-β- glucopyranoside and 3-O-α-rhamnopyranosyl(1→6)-β-glucopyranoside. Moreover, we have detected the presence of three phenolic acids.

Beyond the Immune System: The Role of Resident Cells in Asthma and COPD

Beyond the Immune System: The Role of Resident Cells in Asthma and COPD

Metabolic Fingerprinting of Tussilago farfara L. Using 1H‐NMR Spectroscopy and Multivariate Data Analysis

The flower bud of Tussilago farfara L. is widely used for the treatment of coughs, bronchitis and asthmatic disorders in traditional Chinese medicine. In Europe, the plant has been used as herbal remedies for virtually the same applications, but the leaves are preferred over flowers. To systematically evaluate the chemical profiles of Tusssilago farfara leaves and flowers along with the identification of the polar and non-polar metabolites. Metabolic profiling carried out by means of ¹H-NMR spectroscopy and multivariate data analysis was applied to crude extracts from flowers and leaves. Metabolites were identified directly from the crude extracts through one-dimensional and two-dimensional NMR spectra. A broad range of metabolites were detected without any chromatographic separation. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) of ¹H-NMR data provided a clear separation between the samples. The corresponding loadings plot indicated that higher levels of phenylpropanoids, amino acids, organic acids and fatty acids, as well as lower levels of sugars, terpenoids and sterols were present in the leaves, as compared with flowers. For the flowers, more phenylpropanoids were present in fully open flowers, while more sugars and fatty acids were present in flower buds. NMR spectra (one- and two-dimensional) are useful for identifying metabolites, especially for the overlapped signals. The NMR-based metabolomics approach has great potential for chemical comparison study of the metabolome of herbal drugs.

Anti-Asthmatic and Anti-Allergic Activity of Lagenaria siceraria Mol. Standley

The present attempt was aimed to evaluate the anti-asthmatic and anti-allergic activity of the aqueous extract of Lagenaria siceraria leaf (LSA) using various animal models like histamine and acetylcholine induced bronchoconstriction in Guinea pigs, compound 48/80 induced mast cell degranulation in rats and paw edema in mice. LSA exhibited significant and dose dependent bronchodilatory activity at the doses of 150 and 300 mg/kg intraperitonially (i.p.). LSA at the concentrations of 10, 20 and 30 I¼g/ml significantly inhibited compound 48/80 induced mast cell degranulation. The anti inflammatory activity was observed at the doses of 50, 75 and 100 mg/kg (i.p.) against compound 48/80 induced paw edema in rats. These results prove the traditional claim of the drug in treatment of asthmatic disorders.

Metabolomic profiling of the flower bud and rachis of Tussilago farfara with antitussive and expectorant effects on mice

Ethnopharmacological relevanceFlower bud of Tussilago farfara L. is widely used for the treatment of cough, bronchitis and asthmatic disorders in the Traditional Chinese Medicine. However, due to the increasing demands, adulteration with rachis is frequently encountered in the marketplace. No report demonstrated the chemical and pharmacological differences between flower bud and rachis before. Materials and methodsThe water extracts were orally administrated to mice. Ammonia induced mice coughing model was used to evaluate the antitussive activity. The expectorant activity was evaluated by volume of phenol red in mice's tracheas. Metabolites were identified directly from the crude extracts through 1D- and 2D-NMR spectra. A metabolic profiling carried out by 1H NMR spectroscopy and multivariate data analysis was applied to crude extracts from flower bud and rachis. ResultsFlower bud significantly lengthened the latent period of cough, decreased cough frequency caused by ammonia and enhanced tracheal phenol red output in expectorant evaluation. Principal component analysis (PCA) yielded good separation between flower bud and rachis, and corresponding loading plot showed that the phenolic compounds, organic acid, sugar, amino acid, terpene and sterol contributed to the discrimination. ConclusionsThese findings provide pharmacological and chemical evidence that only flower bud can be used as the antitussive and expectorant herbal drug. The high concentration of chlorogenic acid, 3,5-dicaffeoylquinic acid, rutin in flower buds may be related with the antitussive and expectorant effects of Flos Farfara. To guarantee the clinical effect, rachis should be picked out before use.

In Vitro and in Vivo Evaluation of Buccal Bioadhesive Films Containing Salbutamol Sulphate

The aim of present study was to prepare and evaluate buccal bioadhesive films of salbutamol sulphate (SS) for the treatment of asthma. The films were designed to release the drug for a prolonged period of time so as to reduce the frequency of administration of the available conventional dosage forms of SS. The different proportions of sodium carboxymethylcellulose (SCMC) and Carbopol 940P (CP 940P) were used for the preparation of films. Carbopol was used to incorporate the desired bioadhesiveness in the films. The films were prepared by solvent casting method and evaluated for bioadhesion, in vitro drug release and anti asthmatic effect (bronchoprotection) in histamine induced bronchospasm of guinea pigs. In vitro drug release from the film was determined using a modified Franz diffusion cell while bioadhesiveness was evaluated with a modified two-arm balance using guinea pig buccal mucosa as a model tissue. Films containing SCMC : CP 940P ratio of 76 : 24 was found to be the best with moderate swelling along with favorable bioadhesion force and in vitro drug release. The drug release mechanism was found to follow non-Fickian diffusion as release mechanism. The prolonged in vivo effect (bronchoprotection) obtained from the buccal bioadhesive film of SS administered via buccal route may improve the treatment of asthmatic disorders by reducing the frequency of administration which is associated with the tolerance effect of SS. Additionally for the clinical benefit, it is also expected to reduce the major adverse effects of SS such as tachycardia and arrhythmias via buccal absorption.

What the asthma end points we know and love do and do not tell us

Asthma is a disorder characterized by common features of reversible airflow obstruction and bronchial hyperreactivity in the setting of airway mucosal and submucosal inflammation. However, the clinical manifestations are syndromic and not unimodal. There is marked variability in severity of symptoms, natural history, risks of adverse outcomes, pathologic characteristics, and response to therapy. Understanding the relationship between these factors has been complicated by the variability of outcomes and the lack of correlation between them. There is a striking absence of correlation among the pathologic, physiologic, and clinical manifestations of the asthmatic disorders. Lung function tends to correlate poorly with clinical outcomes, and there is only modest correlation between clinical outcomes. Response to therapy is variable both externally (between patients) and internally, depending on which outcome is evaluated. A more complete understanding of the variability of disease and the genetic and environmental causes of the variability likely will change how we approach asthma and its therapy.

04/01039 Japanese experiences of environmental management: Matsuo, T. Water Science and Technology, 2003, 47, (1), 7–14

This chapter discusses the health effects of air pollution. Any air pollution control program may not have any practical results until the mechanism of air pollution and its health effects are revealed by epidemiological studies. The first step of an epidemiological study of air pollution is to establish an association between pollutant exposures and health effects. In the postwar period there was an enormous increase in the population of Tokyo, and a vast amount of coal and gasoline was being consumed due to the increasing number of motor vehicles and, thus, the number of days with dense smog had begun to increase. Japan has seen no severe air pollution episodes similar to those seen in London in 1952 and in Donora in 1948. However, exception to this might be Tokyo–Yokohama asthma. Outbreak of this disease was felt during 1946 and 1949. Air pollution in the city of Yokkaichi was a major environmental problem, ranking with the Minamata disease and Itai-itai disease. This led to an epidemic of chronic obstructive lung disease including bronchial asthma (the Yokkaichi asthma). An abnormally high incidence of asthmatic disorders was observed in the polluted districts. Air pollution does not consist of a single pollutant but many different kinds of pollutants. The chapter discusses the health effects of NO2 and some other types of air pollution.