A mucoactive drug carbocisteine ameliorates steroid resistance in rat COPD model

Song, Yun; Yu, Ping; Lü, Juanjuan; Lu, Haozhong; Zhu, Liang; Yu, Zhihua; Chen, Hongzhuan; Cui, Yong-Yao

doi:10.1016/j.pupt.2016.06.003

Cited by 13 publications

(10 citation statements)

References 41 publications

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“…Chronic obstructive pulmonary disease (COPD), a complex inflammatory disease, involves the destruction of the lung parenchyma and chronic inflammation of the peripheral airways, which leads to progressive airway narrowing and dyspnea (Lamprecht et al, 2011 ; Song et al, 2016 ). COPD has posed a substantial health care burden on many countries for centuries.…”

Section: Introductionmentioning

confidence: 99%

Establishment and Evaluation of a Rat Model of Sidestream Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease

et al. 2018

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Chronic obstructive pulmonary disease (COPD) is a common cause of mortality worldwide. The current lack of an animal model that can be established within a certain time frame and imitate the unique features of the disease is a major limiting factor in its study. The present study established and evaluated an animal model of COPD that represents the early and advanced stage features using short-, middle-, and long-term sidestream cigarette smoke (CS) exposure. One hundred and nine Sprague–Dawley rats were randomly divided into 10 groups for different periods of sidestream CS exposure or no exposure (i.e., normal groups). The rats were exposed to CS from 3R4F cigarettes in an exposure chamber. Histological analysis was performed to determine pathological changes. We also conducted open-field tests, lung function evaluations, and cytokine analysis of the blood serum, bronchoalveolar lavage fluid, and lung tissue. The lung tissue protein levels, blood gases, and were also analyzed. As the CS exposure time increased, the indicators associated with oxidative stress, inflammatory responses, and airway remodeling were greater in the CS exposure groups than in the normal group. At 24 and 36 weeks, the COPD model rats displayed the middle- and advanced-stage features of COPD, respectively. In the 8-week CS exposure group, after the CS exposure was stopped for 4 weeks, inflammatory responses and oxidative responses were ameliorated and lung function exacerbation was reduced compared with the 12-week CS exposure group. Therefore, we established a more adequate rat model of sidestream CS induced COPD, which will have great significance for a better understanding of the pathogenesis of COPD and drug effectiveness evaluation.

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Section: Introductionmentioning

confidence: 99%

Establishment and Evaluation of a Rat Model of Sidestream Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease

et al. 2018

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“…One of the most significant BP pathways was response to drug, which is also considered as drug sensitivity/resistance and has essential implications for COPD treatment. 28 The second was protein autophosphorylation, which initiates or inhibits downstream signaling through its metamorphosis. For example, EGFR regulates several downstream signaling pathways through its phosphorylation, and participates in the pathological process of COPD.…”

Section: Resultsmentioning

confidence: 99%

Unraveling the Molecular Mechanism of Xuebijing Injection in the Treatment of Chronic Obstructive Pulmonary Disease by Combining Network Pharmacology and Affymetrix Array

Lin

Zhang

et al. 2022

Natural Product Communications

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Xuebijing injection (XBJ), one of the classical prescriptions for treating inflammation-related diseases, has been used to chronic obstructive pulmonary disease (COPD) in clinical practice. However, its molecular mechanism is still unclear. Network pharmacology combined with Affymetrix arrays and molecular docking techniques were applied to explore the molecular mechanism of XBJ for COPD. Predictive analysis of 728 active compounds in XBJ and 6 sets of Affymetrix arrays expression data resulted in 106 potential therapeutic targets. Next, based on the active compound-co-target network topology analysis, most of these targets were found to be modulated by quercetin, myricetin, and ellagic acid. Furthermore, protein–protein interaction (PPI) analysis revealed that the key targets may be EGFR, STAT3, AKT1, CCND1, MMP9, AR, ESR1, and PTGS2. Then, by constructing a component-target-pathway network, we found that XBJ was a multi-pathway, multi-target, multi-compound synergistic therapy for COPD, and four key targets were involved in the FoxO signaling pathway. Luteolin and salvianolic acid b had the optimal binding ability to several key proteins. Therefore, we hypothesize that quercetin, myricetin, ellagic acid, luteolin, and salvianolic acid b mainly contribute to the therapeutic effect of XBJ on COPD by modulating the FoxO signaling pathway by regulating EGFR, STAT3, AKT1, and CCND1. XBJ exerts anti-inflammatory and antioxidative stress effects through the PI3K/Akt/FoxO axis combined with MMP9, AR, ESR1, and PTGS2 to regulate other signaling pathways.

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“…A previous study on biomarkers that predict tracheal stenosis caused by metal stent implantation demonstrated that elevated IL-8 expression levels were predictive of the development of tracheal stenosis in rabbits (53). Furthermore, a previous study using a murine coPd model revealed that carbocisteine improved airway remodeling, including airway epithelium, smooth muscle thickness, airway fibrosis and decreased levels of α-smooth muscle actin and TGF-β1, by increasing HDAC2 expression and activity (54). In the current study, tracheal mucosal epithelial hyperplasia and fibroblast hyperplasia were not improved and there was no significant reduction in collagen synthesis in the PEN and BUD groups compared with the CON group, which was consistent with the lack of a significant upregulation effect of PEN or BUD on the expression of HDAC2 in tracheal tissues.…”

Section: Discussionmentioning

confidence: 97%

Protective effects of different anti‑inflammatory drugs on tracheal stenosis following injury and potential mechanisms

et al. 2021

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Tracheal stenosis following injury cannot be effectively treated. The current study compared the protective effects of different anti-inflammatory drugs on tracheal stenosis and investigated their possible mechanisms. rabbit tracheal stenosis models following injury were constructed and confirmed using hematoxylin and eosin (H&E) staining. A total of 30 rabbits were divided into the control (CON), penicillin (PEN), erythromycin (ERY), budesonide (BUD) and PEN + ERY + BUD groups (n=6). Stenotic tracheal tissue, serum and bronchoalveolar lavage fluid (BALF) were collected 10 days after continuous treatment. Pathological changes in the tracheas were observed by H&E staining. Histone deacetylase 2 (HDAC2) expression in tracheal tissues was detected by immunofluorescence. Immunohistochemistry was performed to detect collagen I (Col-I) and collagen III (Col-III) levels in tracheal tissues. Transforming growth factor β1 (TGF-β1), vascular endothelial growth factor (VEGF) and interleukin 8 (IL-8) levels in serum and BALF samples were determined using ELISA kits. Western blotting detected HDAC2, IL-8, TGF-β1 and VEGF levels in tracheal tissues. H&E staining demonstrated that tracheal epithelial hyperplasia and fibroblast proliferation in the ERY and PEN + ERY + BUD groups markedly improved compared with the CON group. Furthermore, in tracheal tissues, HDAC2 expression was significantly increased and IL-8, TGF-β1, VEGF, Col-I and Col-III levels were significantly decreased in the ERY and PEN + ERY + BUD groups compared with the con group. additionally, the results for the PEN + ERY + BUD were more significant compared with the ERY group. In serum and BALF samples, IL-8, TGF-β1 and VEGF levels in the ERY and PEN + ERY + BUD groups were significantly lower compared with the CON group, with the results of the PEN + ERY + BUD group being more significant compared with the ERY group. There were no significant differences between the PEN, BUD and CON groups. ERY inhibited tracheal granulation tissue proliferation and improved tracheal stenosis following injury and synergistic effects with PEN and BUD further enhanced these protective effects. The mechanism may involve HDAC2 upregulation and inhibition of local airway and systemic inflammatory responses.

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A mucoactive drug carbocisteine ameliorates steroid resistance in rat COPD model

Cited by 13 publications

References 41 publications

Establishment and Evaluation of a Rat Model of Sidestream Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease

Establishment and Evaluation of a Rat Model of Sidestream Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease

Unraveling the Molecular Mechanism of Xuebijing Injection in the Treatment of Chronic Obstructive Pulmonary Disease by Combining Network Pharmacology and Affymetrix Array

Protective effects of different anti‑inflammatory drugs on tracheal stenosis following injury and potential mechanisms

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