Inhibitory effect of Xiaochuan pill on obstinate cough and its role in regulation of TLR4MyD88NFκBp65 signaling pathway.
10.11817/j.issn.1672-7347.2020.190452
- Author:
Dongdong PENG
1
,
2
;
Xuewu LIU
1
,
3
;
Dan ZHANG
1
,
3
;
Dejian JIANG
1
,
4
;
Fei WANG
5
Author Information
1. Hunan Provincial Center of Drug Safety Evaluation and Research of Drugs
2. Hunan Key Laboratory of Pharmacodynamics and Safety Evaluation of New Drugs, Changsha 410331. pengdongdong@hnse.org.
3. Hunan Key Laboratory of Pharmacodynamics and Safety Evaluation of New Drugs, Changsha 410331.
4. Hunan Key Laboratory of Pharmacodynamics and Safety Evaluation of New Drugs, Changsha 410331. jiangdejian@hnse.org.
5. Department of Respiration, Shanghai Tenth People's Hospital, Shanghai 200040, China.
- Publication Type:Journal Article
- Keywords:
TLR4-MyD88-NF-κBp65 signaling pathway;
Xiaochuan pill;
cough variant asthma;
obstinate cough
- MeSH:
Animals;
Cough;
Myeloid Differentiation Factor 88;
NF-kappa B;
Rats;
Signal Transduction;
Toll-Like Receptor 4;
Tumor Necrosis Factor-alpha
- From:
Journal of Central South University(Medical Sciences)
2020;45(7):774-781
- CountryChina
- Language:English
-
Abstract:
OBJECTIVES:Cough variant asthma (CVA) is the main cause of obstinate cough. This study aimed to observe the therapeutic effect of Xiaochuan pill on CVA in a rat model, and to explore the mechanisms.
METHODS:The rats were sensitized and challenged with 4% ovaibumin (OA) and 2% Al(OH) to establish the CVA models. They were treated with Xiaochuan pill (at the dose of 0.9, 1.8, 3.6 g/kg) or montelukast sodium once a day for 14 days. After 7 and 14 days of intervention, 5 and 10 rats were randomly selected from each group to collect bronchoalveolar lavage fluid (BALF), trachea, and lungs. The number of white blood cells (WBC) and eosinophils (EOS), and the levels of IL-1β, TNF- α, and IFN-γ in BALF were detected. Histopathological examination of lung tissue was performed to observe the histomorphological changes. The expressions of TLR4, MyD88, NF-κBp65, and p-p65 in lung tissue were detected by Western blotting.
RESULTS:The numbers of WBC and EOS in BALF of CVA rats were significantly decreased by Xiaochuan pill (<0.05 or <0.01). The hyperplasia of tracheal, bronchial mucosa and the infiltration of inflammatory cells in lung were alleviated obviously. After 14 d of intervention, high dose of Xiaochuan pill significantly increased the level of IFN- γ (<0.01), reduced the levels of IL-1β (<0.05) and TNF-α (<0.05), and decreased the expressions of TLR4, MyD88, p65, and p-p65 (<0.05 or <0.01).
CONCLUSIONS:Xiaochuan pill exerts the significant therapeutic effect on obstinate cough in rats. The mechanism of action may be related to the regulation of TLR4-MyD88-NF-κBp65 signaling pathway as well as the inflammation and immune response.
