scholarly journals Loki Zupa alleviates inflammatory and fibrotic responses in cigarette smoke induced rat model of chronic obstructive pulmonary disease

2020 ◽  
Author(s):  
Nabijan Mohammadtursun ◽  
Qiuping Li ◽  
Muhammadjan Abuduwaki ◽  
Shan Jiang ◽  
Hu Zhang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Blood Serum ◽  
Cigarette Smoke ◽  
Rat Model ◽  
Lavage Fluid ◽  
Inflammatory Factors ◽  
Chronic Obstructive ◽  
Model Group ◽  
Obstructive Pulmonary Disease ◽  
Bronchial Alveolar Lavage Fluid

Abstract Background: Loki zupa formula is kind of a traditional medicines which used to treat airway diseases, especially those caused by abnormal phlegm, such as cough, asthma and chronic bronchitis. The study aim was to explore the anti-inflammatory and anti-remodeling effects of Loki zupa by using a cigarette-smoke induced rat model of chronic obstructive pulmonary disease.Methods: The rats were divided into five groups: the normal group, the model group, the LZ 4g/kg and LZ8g/kg group, and the positive control group. Rats were exposed to cigarette smoke for 24 weeks to induce a COPD rat model. Lung function was assessed. Histopathological changes were recorded using Haematoxylin-eosin and Masson’s tricrome staining. Mucus hypersecretion was evaluated by PAS staining. Inflammatory factors were measured in blood serum and bronchial alveolar lavage fluid using an enzyme-linked immunosorbent assay. Malondialdehyde and superoxide dismutase and glutathione S—transferase levels were tested by biochemical methods. Gene expression patterns were evaluated using GN-GeneChip Clariom S Array for rat from Affymetrix. And top upregulated and downregulated genes validated by qPCR. And these genes was also compared with gene transcriptomic data from smoker patients with emphysema and non-smokers in GEO dataset. IL-6/PLAGA2A signalling protein expression was assessed by western blot and immunohistochemistry. TGF-β1and smad2/3 signalling expressions were analysed by western Blot.Results Loki zupa improved COPD rats lung function as compared to the model group and pathological changes including inflammatory cell infiltration and goblet cell metaplasia was alleviated in rats treated with Loki zupa Inflammatory factors IL-6, TNF-α, IL-1β and TGF-β1 decreased while significant increase was observed in blood serum IL-10 content in rats treated with Loki zupa . And IL-6 and TNF-α level in bronchial alveolar lavage fluid showed same expression trend in blood serum, while there was no change in MMP-9 content. It also increased antioxidant enzyme SOD and GPX activity while reducing the lipid peroxidation. Gene microarray analysis showed that there were 355 differentially expressed gene in LZ treated COPD rat lung as compared to model group. Both microarray and qPCR results showed that top differentially expressed genes nxt1(up regulated ) and pla2g2a (down regulated) expression were also reversed by LZ treatment. And protein expression level of IL-6 and pla2g2a was also elevated in CS exposed rats while significant reduction was observed in LZ treated rats. Accordingly, Loki zupa inhibited Collagen-1 upstream protein expression of TGF-β/smad2/3 signalling pathway. Conclusion: These results demonstrated that Loki zupa showed protective effects in the lung of the COPD rat model. This mainly because of Loki zupa exerts anti-inflammatory effects by blocking IL-6/pla2g2a signalling and inhibiting inflammatory gene expression and attenuates fibrotic responses by inhibiting TGF-β/smad2/3 signalling pathway.

scholarly journals Loki Zupa alleviates inflammatory and fibrotic responses in cigarette smoke induced rat model of chronic obstructive pulmonary disease

2020 ◽  
Author(s):  
Nabijan Mohammadtursun ◽  
Qiuping Li ◽  
Muhammadjan Abuduwaki ◽  
Shan Jiang ◽  
Hu Zhang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Blood Serum ◽  
Cigarette Smoke ◽  
Rat Model ◽  
Lavage Fluid ◽  
Inflammatory Factors ◽  
Chronic Obstructive ◽  
Model Group ◽  
Tnf Α ◽  
Bronchial Alveolar Lavage Fluid

Abstract BackgroundLoki zupa formula is kind of a traditional medicines which used to treat airway diseases, especially those caused by abnormal phlegm, such as cough, asthma and chronic bronchitis. The study was to explore the anti-inflammatory and anti-remodeling effects of Loki zupa using a cigarette-smoke induced rat model of chronic obstructive pulmonary disease.MethodsThe rats were divided into five groups: the normal group, the model group, the LZ 4 g/kg and LZ8g/kg group, and the positive control group. Rats were exposed to cigarette smoke for 24 weeks to induce a COPD rat model. Lung function was assessed. Histopathological changes were recorded using Haematoxylin-eosin. Mucus hypersecretion was evaluated by PAS staining. Inflammatory factors were measured in blood serum and bronchial alveolar lavage fluid using an enzyme-linked immunosorbent assay. Malondialdehyde and superoxide dismutase and glutathione S—transferase levels were tested by biochemical methods. Gene expression patterns were evaluated using GN-GeneChip Clariom S Array for rat from Affymetrix. And top upregulated and downregulated genes validated by qPCR. And these genes was also compared with gene transcriptomic data from smoker patients with emphysema and non-smokers in GEO dataset. IL-6/PLAGA2A signalling protein expression was assessed by western blot and immunohistochemistry. TGF-β1and smad2/3 signalling expressions were analysed by western Blot.Results Loki zupa improved COPD rats lung function as compared to the model group and pathological changes including inflammatory cell infiltration and goblet cell metaplasia was alleviated in rats treated with Loki zupa . Inflammatory factors IL-6, TNF-α, IL-1β and TGF-β1 decreased while significant increase was observed in blood serum IL-10 content in rats treated with Loki zupa . And IL-6 and TNF-α level in bronchial alveolar lavage fluid showed same expression trend in blood serum, while there was no change in MMP-9 content. It also increased antioxidant enzyme SOD activity while reducing the lipid peroxidation. Gene microarray analysis showed there were 355 differentially expressed gene in LZ treated COPD rat lung as compared to model group. Both microarray and qPCR results showed that top differentially expressed genes nxt1(up regulated ) and pla2g2a (down regulated) expression were also reversed by LZ treatment. And protein expression level of IL-6 and pla2g2a was also elevated in CS exposed rats while significant reduction was observed in LZ treated rats. Accordingly, Loki zupa inhibited Collagen-1 upstream protein expression of TGF-β/smad2/3 signalling pathway. Conclusion These results demonstrated that Loki zupa showed protective effects in the lung of the COPD rat model. This mainly because of Loki zupa exerts anti-inflammatory effects by blocking IL-6/pla2g2a signalling and inhibiting inflammatory gene expression and attenuates fibrotic responses by inhibiting TGF-β/smad2/3 signalling pathway.

scholarly journals Baicalin Exerts Anti-Airway Inflammation and Anti-Remodelling Effects in Severe Stage Rat Model of Chronic Obstructive Pulmonary Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Genfa Wang ◽  
Nabijan Mohammadtursun ◽  
Yubao Lv ◽  
Hongying Zhang ◽  
Jing Sun ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Bronchoalveolar Lavage ◽  
Cigarette Smoke ◽  
Rat Model ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Chronic Obstructive ◽  
Airway Remodelling ◽  
Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a worldwide epidemic. Current approaches are disappointing due to limited improvement of the disease development. The present study established 36-week side stream cigarette smoke induced rat model of COPD with advanced stage feature and evaluted the effects of baicalin on the model. Fifty-four Sprague–Dawley rats were randomly divided into six groups including room air control, cigarette smoke exposure, baicalin (40 mg/kg, 80 mg/kg, and 160 mg/kg), and budesonide used as a positive control. Rats were exposed to cigarette smoke from 3R4F research cigarettes. Pulmonary function was evaluated and pathological changes were also observed. Cytokine level related to airway inflammation and remodelling in blood serum, bronchoalveolar lavage fluid, and lung tissue was determined. Blood gases and HPA axis function were also examined, and antioxidant levels were quantified. Results showed that, after treatment with baicalin, lung function was improved and histopathological changes were ameliorated. Baicalin also regulated proinflammatory and anti-inflammatory balance and also airway remodelling and anti-airway remodelling factors in blood serum, bronchoalveolar lavage fluid, and lung tissue. Antioxidant capacity was also increased after treatment with baicalin in COPD rat model. HPA axis function was improved in baicalin treated groups as compared to model group. Therefore, baicalin exerts lung function protection, proinflammatory and anti-inflammatory cytokine regulation, anti-airway remodelling, and antioxidant role in long term CS induced COPD model.

scholarly journals FSTL1 aggravates cigarette smoke-induced airway inflammation and airway remodeling by regulating autophagy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ying Liu ◽  
Jiawei Xu ◽  
Tian Liu ◽  
Jinxiang Wu ◽  
Jiping Zhao ◽  
...  
Keyword(s):  
Lung Function ◽  
Airway Inflammation ◽  
Cigarette Smoke ◽  
Airway Remodeling ◽  
Critical Factor ◽  
Lavage Fluid ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Impaired Lung Function

Abstract Background Cigarette smoke (CS) is a major risk factor for Chronic Obstructive Pulmonary Disease (COPD). Follistatin-like protein 1 (FSTL1), a critical factor during embryogenesis particularly in respiratory lung development, is a novel mediator related to inflammation and tissue remodeling. We tried to investigate the role of FSTL1 in CS-induced autophagy dysregulation, airway inflammation and remodeling. Methods Serum and lung specimens were obtained from COPD patients and controls. Adult female wild-type (WT) mice, FSTL1± mice and FSTL1flox/+ mice were exposed to room air or chronic CS. Additionally, 3-methyladenine (3-MA), an inhibitor of autophagy, was applied in CS-exposed WT mice. The lung tissues and serum from patients and murine models were tested for FSTL1 and autophagy-associated protein expression by ELISA, western blotting and immunohistochemical. Autophagosome were observed using electron microscope technology. LTB4, IL-8 and TNF-α in bronchoalveolar lavage fluid of mice were examined using ELISA. Airway remodeling and lung function were also assessed. Results Both FSTL1 and autophagy biomarkers increased in COPD patients and CS-exposed WT mice. Autophagy activation was upregulated in CS-exposed mice accompanied by airway remodeling and airway inflammation. FSTL1± mice showed a lower level of CS-induced autophagy compared with the control mice. FSTL1± mice can also resist CS-induced inflammatory response, airway remodeling and impaired lung function. CS-exposed WT mice with 3-MA pretreatment have a similar manifestation with CS-exposed FSTL1± mice. Conclusions FSTL1 promotes CS-induced COPD by modulating autophagy, therefore targeting FSTL1 and autophagy may shed light on treating cigarette smoke-induced COPD.

scholarly journals Galgeun-tang Attenuates Cigarette Smoke and Lipopolysaccharide Induced Pulmonary Inflammation via IκBα/NF-κB Signaling

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2489 ◽  
Author(s):  
Na-Rae Shin ◽  
Chul Kim ◽  
Chang-Seob Seo ◽  
Je-Won Ko ◽  
Young-Kwon Cho ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Inflammatory Cell ◽  
Pulmonary Inflammation ◽  
Water Extract ◽  
Lavage Fluid ◽  
Chronic Obstructive ◽  
Necrosis Factor Alpha ◽  
Obstructive Pulmonary Disease ◽  
Cell Counts ◽  
Oxide Synthase

Galgeun-tang water extract (GGWE) is used to treat various diseases such as the common cold, eczema and asthma in China and Korea. In this study, we investigated the anti-inflammatory effect of GGWE using a cigarette smoke (CS)- and lipopolysaccharide (LPS)-induced induced pulmonary inflammation mouse model. The mice were exposed to CS for a total of seven days (eight cigarettes per day for 1 h) and LPS was administered intranasally to mice on day 4. GGWE was administered by oral gavage at doses of 50 mg/kg or 100 mg/kg 1 h before exposure to CS. GGWE decreased inflammatory cell counts, and expression of inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) in bronchoalveolar lavage fluid (BALF) from mice exposed to CS and LPS. GGWE reduced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), as well as the phosphorylation of inhibitor of kappa-B subunit alpha (IκBα) and nuclear factor kappa-B (NF-κB) in CS- and LPS-exposed mice. Histological examinations revealed that GGWE suppressed inflammatory cell infiltration into lung tissue compared to untreated CS- and LPS-exposed mice. In conclusion, GGWE effectively suppressed CS- and LPS-induced pulmonary inflammation. Our results indicate that GGWE may be used as a protective drug to control pulmonary inflammation diseases such as chronic obstructive pulmonary disease.

Nrf2 Improves Airway Goblet Cell Metaplasia in Chronic Obstructive Pulmonary Disease (COPD) and Its Mechanism

2022 ◽  
Vol 12 (4) ◽  
pp. 739-746
Author(s):  
Zhihong Qiu ◽  
Li Yan ◽  
Juan Xu ◽  
Xiaojun Qian
Keyword(s):  
Protein Expression ◽  
Goblet Cell ◽  
Inflammatory Cells ◽  
Cell Number ◽  
Chronic Obstructive ◽  
Model Group ◽  
Down Regulation ◽  
Obstructive Pulmonary Disease ◽  
Pas Staining

Objective: The aim of our research was to evaluate Nrf2 in COPD treatment and relative mechanism by vivo study. Materials: The mice were divided into Normal, Model and CCL16 groups. Measuring Pathology and goblet cell number by HE or AB/PAS staining; Evaluating apoptosis cell number by TUNEL assay; using flow separation to analysis inflammatory cells in difference groups; MAPK and NF-κB(p65) protein expression were evaluated by IHC assay in tissues; Total protein concentration of MUC5AC, Nrf2, Bax and Bcl-2 were evaluated by WB assay. Results: Compared with Normal group, the pathology was deteriorate and goblet cell number were significantly up-regulation in Model group, apoptosis goblet cell number were significantly depressed (P < 0.001), lympbocyte rate and hypertrophic rate were significantly down-regulation and Eosinophils rate, Macrophage rate and Neutrophils rate were significantly up-regulation (P < 0.001, respectively) in Model group. By IHC assay, MAPK and NF-κB(p65) proteins expression significantly increased (P < 0.001, respectively) in Model group; by WB assay, MUC5AC and Bcl-2 protein expression were significantly up-regulation and Nrf2 and Bax proteins expression were significantly down-regulation (P < 0.001, respectively) in Model group. Nrf2 supplement, the COPD were significantly improved with relative inflammatory cells rates significantly improving and relative proteins improving. Conclusion: Nrf2 could improve COPD by inducing goblet cell apoptosis increasing via regulation MAPK/NF-κB(p65) pathway in vivo study.

Role of the IL-33/ST2 axis in cigarette smoke-induced airways remodelling in chronic obstructive pulmonary disease

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2020-214712
Author(s):  
Qiong Huang ◽  
Chen Duo Li ◽  
Yi Ran Yang ◽  
Xiao Feng Qin ◽  
Jing Jing Wang ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Lavage Fluid ◽  
Chronic Obstructive ◽  
Tissue Remodelling ◽  
Tissue Samples ◽  
Obstructive Pulmonary Disease ◽  
Interleukin 33 ◽  
Multiple Organs

BackgroundEfficient therapy and potential prophylaxis are confounded by current ignorance of the pathogenesis of airway remodelling and blockade in COPD.ObjectiveTo explore the role of the IL-33/ST2 axis in cigarette smoke (CS) exposure-induced airways remodelling.MethodsC57BL/6, BALB/c and IL-1RL1-/- mice exposed to CS were used to establish an animal surrogate of COPD (air-exposed=5~8, CS-exposed=6~12). Hallmarks of remodelling were measured in mice. Cigarette smoke extract (CSE)-induced proliferation and protein production in vitro by fibroblasts in the presence of anti-interleukin-33 (anti-IL-33) or hST2 antibodies were measured. Expression of IL-33 and ST2 and other remodelling hallmarks were measured, respectively, in bronchoalveolar lavage fluid (BALF) (controls=20, COPD=20), serum (controls=59, COPD=90) and lung tissue sections (controls=11, COPD=7) from patients with COPD and controls.ResultsWild-type mice exposed to CS elevated expression of hallmarks of tissue remodelling in the lungs and also in the heart, spleen and kidneys, which were significantly abrogated in the IL-1RL1-/- mice. Fibroblasts exposed to CSE, compared with control, exhibited early cellular translocation of IL-33, accompanied by proliferation and elevated protein synthesis, all inhabitable by blockade of IL-33/ST2 signalling. Expression of IL-33 and ST2 and hallmarks of tissue remodelling were significantly and proportionally elevated in BALF, serum and tissue samples from patients with COPD.ConclusionsExposure to CS induces remodelling changes in multiple organs. The data support the hypothesis that CS-induced lung collagen deposition is at least partly a result of CS-induced IL-33 translocation and release from local fibroblasts.

Electroacupuncture Reduces Hypothalamic and Medullary Expression of Orexins and their Receptors in a Rat Model of Chronic Obstructive Pulmonary Disease

2018 ◽  
Vol 36 (5) ◽  
pp. 312-318 ◽  
Author(s):  
Xin-Fang Zhang ◽  
Qin Qin ◽  
Wen-Ye Geng ◽  
Chuan-Wei Jiang ◽  
Yong Liu ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Protein Expression ◽  
Pulmonary Function ◽  
Pulmonary Disease ◽  
Rat Model ◽  
Normal Group ◽  
Cigarette Smoke Exposure ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease

Objectives Decreased lung function in chronic obstructive pulmonary disease (COPD) is correlated with abnormal excitability of the respiratory centre where orexin neuropeptides from the hypothalamus are responsible for regulating respiration. We hypothesised that improvements in pulmonary function with electroacupuncture (EA) may be related to orexins in a rat model of COPD. Methods The COPD model was established by cigarette smoke exposure and lipopolysaccharide injection. Modelled rats received EA at BL13 and ST36 for two weeks, after which lung function was tested. Orexin levels in the hypothalamus and medulla were detected by ELISA, while mRNA/protein expression and localisation of orexins and their receptors were investigated using real time PCR, Western blotting and immunohistochemistry, respectively. Results The decrease in lung function observed in COPD rats was improved after EA treatment. Orexin levels in the hypothalamus and medulla were significantly higher in COPD rats than in normal rats, but were significantly reduced in the EA-treated group. There was a negative correlation between orexin content and lung function. In the hypothalamus, mRNA and protein expression and immunoreactivity of orexins were significantly higher in the COPD group than in the normal group, but a significant decrease was observed after EA. In the medulla, the expression and immunoreactivity of orexin receptors were significantly higher in the COPD group than in the normal group, but a significant decrease was observed after EA. Conclusions The positive effect of EA on pulmonary function in COPD rats may be related to downregulation of orexins and their receptors in the medulla.

Chrysene accelerates the proceeding of chronic obstructive pulmonary disease with the aggravation of inflammation and apoptosis in cigarette smoke exposed mice

2020 ◽  
pp. 096032712097934
Author(s):  
Yuan Gao ◽  
Xinjia Zhou ◽  
Yan Zhou ◽  
Wei Zhang ◽  
Li Zhao
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Cigarette Smoke ◽  
Molecular Mechanisms ◽  
Smooth Muscle Actin ◽  
Lavage Fluid ◽  
Living Environment ◽  
Chronic Obstructive ◽  
High Morbidity ◽  
Obstructive Pulmonary Disease

Chrysene, one of the basic polycyclic aromatic hydrocarbons (PAHs), has been reported to make damages to human health and living environment. Chronic obstructive pulmonary disease (COPD) is a progressive disorder with high morbidity and mortality. To investigate the role of chrysene in the development of COPD, male C57BL/6 mice were exposed to the cigarette smoke (CS) followed with the administration of chrysene. Morphological analyses indicated that chrysene caused earlier and severer pathological changes in CS-exposed mice. Besides, CS-exposed mice with chrysene treatment showed obvious collagen deposition, elevated α-smooth muscle actin (α-SMA) expression and reduced E-cadherin abundance at earlier stage, which suggested the acceleration and aggravation of pulmonary fibrosis. Moreover, quantification of leukocytes and pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF) and lung tissues implied that chrysene significantly exacerbated the proceeding of inflammation in CS-exposed mice. Furthermore, significantly increased apoptotic rates, augmented expressions of apoptotic related proteins and highly expressed TRPV1 were determined in CS-exposed mice with chrysene treatment, which indicated the association between COPD pathogenesis and TRPV1 channel. In summary, our findings elucidate that chrysene accelerates the development of COPD in a murine model with new molecular mechanisms.

Sign in / Sign up

Export Citation Format

Share Document