scholarly journals Louqin Zhisou Decoction Inhibits Mucus Hypersecretion for Acute Exacerbation of Chronic Obstructive Pulmonary Disease Rats by Suppressing EGFR-PI3K-AKT Signaling Pathway and Restoring Th17/Treg Balance

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Feng Feng ◽  
Jianchao Du ◽  
Yufeng Meng ◽  
Fang Guo ◽  
Cuiling Feng
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Protein Expression ◽  
Pulmonary Disease ◽  
Signaling Pathway ◽  
Acute Exacerbation ◽  
Akt Signaling ◽  
Chronic Obstructive ◽  
Akt Signaling Pathway ◽  
Obstructive Pulmonary Disease ◽  
Mucus Hypersecretion

Airway mucus hypersecretion is the main pathogenic factor in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and the control of mucus secretion is closely associated with survival. Louqin Zhisou decoction (LQZS) has been found to improve lung function and reduce sputum in AECOPD patients, but the mechanism remains unclear. This study aimed to explore the mechanism of LQZS against mucus hypersecretion in lung tissues of rat AECOPD model. Wistar rats were used to establish AECOPD model by intratracheal instillation of LPS in combination with the continuous cigarette smoking. Rats were administrated LQZS/clarithromycin (CAM)/distilled water via gavage every day and all rats were sacrificed after 30 days. BALF and lung tissues were obtained. Lung morphology, cytokines levels, MUC5AC mRNA transcription and protein expression, phosphorylation of the EGFR-PI3K-AKT signaling pathway, and molecules involved in Th17/Treg balance were evaluated. The results demonstrated that LQZS protected rats from decline in pulmonary function and ameliorated lung injury. LQZS treatment decreased the number of goblet cells in airway and suppressed MUC5AC mRNA and protein expression of lung tissues. Furthermore, LQZS attenuated the level of phospho-EGFR, phospho-PI3K and phospho-AKT in AECOPD rats. In addition, LQZS could inhibit the production of proinflammatory cytokines in BALF, including IL-6 and IL-17A and downregulate the secretion of NE and MCP-1, indicating that LQZS could limit inflammatory responses in AECOPD. Moreover, LQZS reversed RORγt and Foxp3 expression, the key transcription factors of Th17 and Treg, respectively. In conclusion, this research demonstrated the inhibitory effects of LQZS against mucus hypersecretion in AECOPD via suppressing EGFR-PI3K-AKT signaling pathway and restoring Th17/Treg balance.

scholarly journals The mechanism and candidate compounds of aged citrus peel (chenpi) preventing chronic obstructive pulmonary disease and its progression to lung cancer

2021 ◽  
Author(s):  
Lin Zhou ◽  
Wenwen Gu ◽  
Fuguang Kui ◽  
Fan Gao ◽  
Yuji Niu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Chronic Obstructive Pulmonary Disease ◽  
Protein Expression ◽  
Pulmonary Disease ◽  
Signaling Pathway ◽  
Mouse Lung ◽  
Chronic Obstructive ◽  
Active Components ◽  
Obstructive Pulmonary Disease ◽  
Citrus Peel

Background: Chronic obstructive pulmonary disease (COPD) is an important risk factor for developing lung cancer. Aged citrus peel (chenpi) has been used as a dietary supplement for respiratory diseases in China. Objective: To explore the mechanism and candidate compounds of chenpi preventing COPD and its progression to lung cancer. Methods: The active components and potential targets of chenpi were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Disease-associated targets of COPD and lung cancer were collected in the Gene Cards and TTD database. The component-target network and PPI network were constructed using the Cytoscape 3.8.0 software. David database was used for GO and KEGG enrichment analysis. The main active components were verified by using the autodock Vina 1.1.2 software. Mouse lung cancer with COPD was induced by cigarette smoking (CS) combined with urethane injection to confirm preventing the effect of hesperetin (the candidate compound of chenpi) on COPD progression to lung cancer and its underlying mechanisms. Results: The network analysis revealed that the key active components of chenpi (nobiletin, naringenin, hesperetin) regulate five core targets (AKT1, TP53, IL6, VEGFA, MMP9). In addition, 103 potential pathways of chenpi were identified. Chenpi can prevent COPD and its progression to lung cancer by getting involved in the PI3K-Akt signaling pathway and MAPK signaling pathway. Molecular docking indicated that hesperetin had better binding activity for core targets. In mouse lung cancer with COPD, treatment with hesperetin dose-dependently improved not only lung tissue injury in COPD but also carcinoma lesions in lung cancer. Meanwhile, hesperetin could suppress the protein expression of AKT1, IL6, VEGFA, MMP9 and up-regulate the protein expression of TP53, and thus reduced the risk of COPD progression to lung cancer. Conclusion: Hesperetin is a candidate compound of chenpi that helps in preventing COPD and its progression to lung cancer by regulating AKT1, IL6, VEGFA, MMP9 and TP53.

Sign in / Sign up

Export Citation Format

Share Document