Article

Protective Effect of Eucalyptus Oil Against Pulmonary Destruction and Inflammation in COPD Rats

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Abstract

Eucalyptus oil (EO), an essential oil isolated from Eucalyptus leaves, was examined for its effect on LPS and Klebsiella pneumoniae - induced COPD in rats. The COPD model was induced by instilling intratracheally with LPS and Klebsiella pneumoniae (K. P). The test compound, EO (30, 100 and 300 mg/kg), Prednisone Acetate (10 mg/kg) or vehicle was instilled intragastrically after three weeks exposure of LPS and K. P, lasted for 4 weeks. EO significantly reduced amounts of inflammatory cells in bronchoalveolar lavage fluid (BALF) and blood, and decreased bronchiolitis, emphysematous changes and thickness of bronchioles. It also significantly reduced the increased AB-PAS-positive goblet cells in bronchioles. Prednisone Acetate attenuated pulmonary inflammation and airway mucus hypersecretion, but no significant difference was found on emphysema. Pretreatment with EO markly reduced the production of proinflammatory cytokines TNF-α and IL-β in lung homogenate, significantly decreased the elevated malondialdehyde (MDA) level and and increased superoxide dismutase (SOD) activity. These findings indicate that EO could exert an protective effect against LPS plus K. P-induced lung indury via inhibition of proinflammatory cytokines production and improvement of anti-oxidant status. Our results provide evidence that EO might have its potential to be a proper candidate drug in the treatment of COPD.

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... COVID-19 hospitalized patients developed at latter phase a syndrome known as cytokine storm or hyperinflammatory syndrome due to immune overactivation that increases the acute respiratory distress and can lead to death 30 . Pretreatment with EEO markedly reduced the production of proinflammatory cytokines which indicates that EEO might have its potential to stop cytokine storm 19 . As well suppression of human lung macrophages inflammatory responses by EEO and its constituent 1,8-cineole was reported 31 . ...
... COPD control by EEO: COPD is associated with increased risk of morbidity in COVID-19 patients 18 . Pretreatment with EEO markedly reduced the production TNF-α and IL-β proinflammatory cytokines, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level which indicates that EEO might have its potential in COPD treatment19 . The anti-inflammatory effect EEO to reduce cytokine release was confirmed also in ex-vivo cultured and stimulated alveolar macrophages from patients with (COPD) 20 . ...
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Eucalyptol, also known as 1,8-cineol, is a monoterpene and has been shown to exert anti-inflammatory and antioxidant effect. It is traditionally used to treat respiratory disorders due to its secretolytic properties. In the present study, we evaluated the effect of 1,8-cineol on pulmonary inflammation in a mouse model of acute lung injury. We found that 1,8-cineol significantly decreased the level of TNF-α and IL-1β, and increased the level of IL-10 in lung tissues after acute lung injury induced by lipopolysaccharide (LPS). It also reduced the expression of nuclear factor kappa B (NF-κB) p65 and toll-like receptor 4 (TLR4), and myeloperoxidase activity in lung tissues. In addition, 1,8-cineol reduced the amounts of inflammatory cells in bronchoalveolar lavage fluid (BALF), including neutrophils and macrophages, and significantly decreased the protein content in BALF and the lung wet/dry weight (W/D) ratio. Its effect on LPS-induced pulmonary inflammation was associated with suppression of TLR4 and NF-κB expressions. Our results provide evidence that 1,8-cineol inhibits acute pulmonary inflammation, indicating its potential for the treatment of acute lung injury.
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Background and aims: Cineole is the main constituent of eucalyptus oil, and it is mainly used as a mucolytic agent in inflammatory airway diseases. With its known mucolytic, bronchodilating, and anti-inflammatory effects, cineole reduces the exacerbation rate in patients suffering from chronic obstructive pulmonary disease. Based on these pharmacodynamic effects, we arrived at the hypothesis that asthma patients would benefit from concomitant therapy with cineole. Methods: As part of a double-blind, placebo-controlled, multicenter study, 247 patients with confirmed asthma were randomly selected according to the guidelines for this study. All patients were administered 200 mg of cineole, or a placebo, three times per day as a concomitant therapy over a period of 6 months. The combined primary outcome measures, which were implemented as a multiple criteria testing process, were improvement of lung function, asthma symptoms, and quality of life. Results: Following the completion of the 6-month treatment period, it was noted that the patient group treated with cineole showed significantly more improvements to the multiple testing criteria than the patients in the placebo group (p = .0027). The statistical significance of the individual outcome measures could also be proven in accordance with the Wei-Lachin procedure (i.e., for Forced expiratory Volume 1 Second, p = .0398; for asthma symptoms, p = .0325; and for Asthma Quality of Life Questionnaire (AQLQ), p = .0475). Conclusion: Concomitant therapy using cineole can lead to notable improvement in lung function and health condition as well as to reduce dyspnea in asthma patients.
Article
Inhalation of lipopolysaccharide (LPS) produces both systemic and pulmonary inflammatory responses. The aim of this study was to further characterize the response to LPS in order to develop a human model suitable for early testing of drug candidates developed for the treatment for chronic obstructive pulmonary disease (COPD). Blood and induced sputum were obtained 4, 24 and 48 h following inhalation of saline and LPS (5 and 50 μg). Blood was analysed for C-reactive protein (CRP), α(1)-antitrypsin and neutrophils/leucocytes, and sputum was analysed for biomarkers of neutrophil inflammation and remodelling activities, i.e. neutrophil elastase (NE) protein/activity and α(1)-antitrypsin. Levels of tumour necrosis factor-α (TNFα) were measured in both blood and sputum. Urine was collected 0-24 and 24-48 h postchallenge, and desmosine, a biomarker of elastin degradation, was measured. Lipopolysaccharide inhalation induced dose-dependent flu-like symptoms and increases in plasma CRP and α(1)-antitrypsin as well as increases in blood neutrophil/leucocyte numbers. Furthermore, LPS produced increases in sputum TNFα and sputum NE activity. Urine levels of desmosine were unaffected by the LPS challenge. All subjects recovered 48 h postchallenge, and indices of inflammatory activity were significantly lower at this observation point cf 24 h postchallenge. Inhalation of LPS in healthy volunteers can be used as a safe and stable model of neutrophil inflammation. Blood/plasma and sputum indices can be employed to monitor the response to LPS. We suggest that this model may be used for initial human studies of novel COPD-active drugs.
Article
Eucalyptus bridgesiana, Cymbopogon martinii, Thymus vulgaris, Lindernia anagallis, and Pelargonium fragrans are five species of herbs used in Asia. Their essential oils were analyzed by GC-MS, and a total of 36 components were detected. The results of our study indicated that, except for the essential oil of P. fragrans, all of the essential oils demonstrated obvious antimicrobial activity against a broad range of microorganisms. The C. martinii essential oil, which is rich in geraniol, was the most effective antimicrobial additive. All of the essential oils demonstrated antioxidant activities on 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay, β-carotene/linoleic acid assay, and nitric oxide radical scavenging assay. Furthermore, the T. vulgaris essential oil, which possesses plentiful thymol, exhibited the highest antioxidant activity. For P. acnes-induced secretion of pro-inflammatory cytokines, the essential oils of P. aeruginosa, C. martinii, and T. vulgaris reduced the TNF-α, IL-1β, and IL-8 secretion levels of THP-1 cells.
Article
To observe the role of bacterial infection in pathogenesis of COPD. The COPD animal model was developed by intranasal repeated injecting Klebsiella pneumoniae(K) or pneumococcal pneumoniae(P) into rat respiratory tract. Histomorphyological changes were observed, PaO2, PaCO2 and right ventricular systolic pressure (RVSP) were analysed. 1 week after injecting K and 4 week after injecting P, the epithelia of bronchioles showed obvious injury. From the 4th week there was severe chronic inflammatory process of bronchioles in 2 experimental groups including thickened wall, narrowed lumen and developed emphysema. In addition, the walls of arterioles accompanying bronchioles were also thickened obviously. Right ventricular systolic pressure raised in 2 experimental groups (P < 0.01). From the 16th week, PaO2 dropped and PaCO2 raised in K group. Repeated injecting intranasally of the proper amount of klebsiella pneumoniae or pneumococcal pneumoniae into rats' lungs can induce rat small airway inflammation and emphysema. Combining with PaO2, PaCO2 and RVSP analysis, we suggest the model established shows main features of COPD.
Article
The role of bacterial pathogens in acute exacerbations of chronic obstructive pulmonary disease is controversial. In older studies, the rates of isolation of bacterial pathogens from sputum were the same during acute exacerbations and during stable disease. However, these studies did not differentiate among strains within a bacterial species and therefore could not detect changes in strains over time. We hypothesized that the acquisition of a new strain of a pathogenic bacterial species is associated with exacerbation of chronic obstructive pulmonary disease. We conducted a prospective study in which clinical information and sputum samples for culture were collected monthly and during exacerbations from 81 outpatients with chronic obstructive pulmonary disease. Molecular typing of sputum isolates of nonencapsulated Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and Pseudomonas aeruginosa was performed. Over a period of 56 months, the 81 patients made a total of 1975 clinic visits, 374 of which were made during exacerbations (mean, 2.1 per patient per year). On the basis of molecular typing, an exacerbation was diagnosed at 33.0 percent of the clinic visits that involved isolation of a new strain of a bacterial pathogen, as compared with 15.4 percent of visits at which no new strain was isolated (P<0.001; relative risk of an exacerbation, 2.15; 95 percent confidence interval, 1.83 to 2.53). Isolation of a new strain of H. influenzae, M. catarrhalis, or S. pneumoniae was associated with a significantly increased risk of an exacerbation. The association between an exacerbation and the isolation of a new strain of a bacterial pathogen supports the causative role of bacteria in exacerbations of chronic obstructive pulmonary disease.
Article
Previous studies of immune response to Haemophilus influenzae after exacerbations of chronic obstructive pulmonary disease (COPD) have yielded contradictory results. Using homologous (infecting) strains and immunoassays to surface-exposed epitopes, we tested the hypothesis that adults with COPD make new antibodies to strain-specific, surface-exposed epitopes on H. influenzae after exacerbations. We collected clinical information, sputum, and serum monthly and during exacerbations from 81 patients with COPD over 56 months. Serum antibodies to H. influenzae after exacerbations associated with H. influenzae in sputum were detected with whole bacterial cell ELISA and bactericidal assays. An immune response to homologous H. influenzae occurred after 22 of 36 (61.1%) exacerbations with newly acquired strains compared with 7 of 33 (21.2%) exacerbations with preexisting strains (odds ratio [OR] = 4.4; 95%, 1.8 to 10.8; p = 0.001). An absence of an immune response was strongly associated with complement sensitivity (OR = 0.03; 95% confidence interval, 0.003 to 0.22; p = 0.001). New bactericidal antibodies developed after exacerbations were highly strain specific, showing bactericidal activity for only 11 of 90 (12.2%) heterologous strains. Development of an immune response to H. influenzae supports its role in causing exacerbations. The strain specificity of the immune response likely represents a mechanism of recurrent exacerbations.
Article
Forty years ago, British investigators developed the hypothesis that recurrent bronchial infections were the reason that some smokers developed progressive airways obstruction and other did not 1. The classical studies of Fletcher et al. 2 were designed to test this proposition. They carried out a prospective study of working males, noting the frequency of respiratory infections, sputum quantity and quality, and rate of loss of lung function in the form of forced expiratory volume in one second (FEV1). They found that chronic cough and sputum production, and recurrent respiratory infections did not relate to lung function decline. They concluded that the chronic bronchitis syndrome (cough, sputum and episodes of acute bronchitis) was an epiphenomenon in so far as the development of chronic obstructive pulmonary disease (COPD) was concerned; both chronic bronchitis and COPD were caused by smoking, but the two were not related. This made sense, since chronic bronchitis symptoms largely reflected pathology in major conducting airways, and airways obstruction was related to lesions in small airways and the lung parenchyma. This view of the pathogenesis of COPD was essentially unchallenged for many years, in a large part because it was hard to do a better study that that of …
Article
To study the effect of Eucalyptus globulus oil on bronchiolitis and mucin hypersecretion in chronic bronchitis induced by lipopolysaccharide in rats. Rat model was established by intratracheal instillation of lipopolysaccharide 0.2 mg. Pathological changes, alteration in bronchoalveolar lavage fluid (BALF) and immunohistochemistry characters were examined after 3 weeks and the effect of E. globulus oil was observed. Characters of pathological manifestations of chronic bronchitis were found after instillation of LPS. Inflammatory cell infiltration and bronchiolitis severity were significantly reduced after administration of E. globulus oil. Especially in 300 mg x kg(-1) treated rats, there were significant decreases of mucin content in BALF and MUC5ac expression in trachea and bronchiole epithelium. Optical density and mucins area% detected by image analysis system were apparently lower than those in model group. E. globulus oil has the anti-inflammatory effect on chronic bronchitis induced by lipopolysaccharide in rats and the inhibitio effect on hypersecretion of airway mucins.
Article
The activity of Eucalyptus globulus essential oil was determined for 120 isolates of Streptococcus pyogenes, 20 isolates of S. pneumoniae, 40 isolates of S. agalactiae, 20 isolates of Staphylococcus aureus, 40 isolates of Haemophilus influenzae, 30 isolates of H. parainfluenzae, 10 isolates of Klebsiella pneumoniae, 10 isolates of Stenotrophomonas maltophilia and two viruses, a strain of adenovirus and a strain of mumps virus, all obtained from clinical specimens of patients with respiratory tract infections. The cytotoxicity was evaluated on VERO cells by the MTT test. The antibacterial activity was evaluated by the Kirby Bauer paper method, minimum inhibitory concentration, and minimum bactericidal concentration. H. influenzae, parainfluenzae, and S. maltophilia were the most susceptible, followed by S. pneumoniae. The antiviral activity, assessed by means of virus yield experiments titered by the end-point dilution method for adenovirus, and by plaque reduction assay for mumps virus, disclosed only a mild activity on mumps virus.
Article
Whether the airway and systemic inflammatory profile in bacterial exacerbations of chronic obstructive pulmonary disease (COPD) is distinct from nonbacterial exacerbations is unclear. Previous studies have not used molecular typing of bacterial pathogens, which is required to accurately define bacterial infection in COPD. The relationship between clinical severity and course of exacerbation and inflammation is also not fully understood. To determine if (1) systemic and airway inflammation is distinct in new bacterial strain exacerbations and (2) clinical severity and resolution of exacerbations is related to airway and systemic inflammation. In a prospective longitudinal cohort study in COPD, sputum and serum samples obtained before, at, and following exacerbations during a 2-year period were studied. Clinical information, molecular typing of bacterial pathogens, sputum IL-8, tumor necrosis factor (TNF)-alpha and neutrophil elastase, and serum C-reactive protein. From 46 patients, 177 exacerbations were grouped as new strain, preexisting strain, other pathogen, and pathogen negative. New strain exacerbations were associated with significantly greater increases from baseline in sputum TNF-alpha and neutrophil elastase, and in serum C-reactive protein compared with the other three groups. Increases in inflammatory markers were similar among the other three groups. Clinical resolution was accompanied by resolution of inflammation to preexacerbation levels, whereas persistent symptoms were paralleled by persistently elevated inflammation. Clinical exacerbation severity was significantly correlated with levels of all four markers. Neutrophilic airway inflammation and systemic inflammation are more intense with well-defined bacterial exacerbations than with nonbacterial exacerbations. Clinical course of exacerbation and inflammation are closely linked.