The traditional Chinese patented medicine Qingke Pingchuan granules alleviate acute lung injury by regenerating club cells

Yuanyuan Wu; Wensi Zhu; Ainiwaer Rouzi; Lin Tong; Linxiao Han; Juan Song; Jianwen Ding; Yu Yan; Miao Li; Ting Pan; Jie Liu; Qin Wang; Yuanlin Song; Jie Shen; Jian Zhou

doi:10.1002/pul2.12138

The traditional Chinese patented medicine Qingke Pingchuan granules alleviate acute lung injury by regenerating club cells

Pulm Circ. 2022 Jul 1;12(3):e12138. doi: 10.1002/pul2.12138. eCollection 2022 Jul.

Authors

Yuanyuan Wu^{1

2}, Wensi Zhu^{1

2}, Ainiwaer Rouzi^{1

2}, Lin Tong^{1

2}, Linxiao Han^{1

2}, Juan Song^{1

2}, Jianwen Ding^{3

4

5}, Yu Yan^{1

2}, Miao Li^{1

2}, Ting Pan^{1

2}, Jie Liu^{1

2}, Qin Wang^{1

2}, Yuanlin Song⁶, Jie Shen^{3

4

5}, Jian Zhou^{1

2

3

6

7}

Affiliations

¹ Department of Pulmonary and Critical Care Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital Fudan University Shanghai China.
² Shanghai Engineering Research Center of Internet of Things for Respiratory Medicine Shanghai China.
³ Research Center for Chemical Injury, Emergency and Critical Medicine of Fudan University Fudan University Shanghai China.
⁴ Key Laboratory of Chemical Injury, Emergency and Critical Medicine of Shanghai Municipal Health Commission Fudan University Shanghai China.
⁵ Center of Emergency and Critical Medicine in Jinshan Hospital of Fudan University Fudan University Shanghai China.
⁶ Shanghai Institute of Infectious Disease and Biosecurity Fudan University Shanghai China.
⁷ Shanghai Key Laboratory of Lung Inflammation and Injury Shanghai China.

Abstract

Qingke Pingchuan granules (QKPCG), a patented traditional Chinese medicine, clinically, are recommended for acute tracheobronchitis, cough, community-acquired pneumonia, and other respiratory diseases. However, its potential protective effect and mechanism of action in acute lung injury (ALI) have not been explored. We aimed to explore the mechanisms underlying the protective role of QKPCG in ALI. The therapeutic efficacy of QKPCG was investigated in a lipopolysaccharide (LPS)-induced ALI mouse model. Mice were divided into three groups, namely, the Control, LPS, and LPS + QKPCG groups. Mice in the LPS + QKPCG group were administered QKPCG intragastrically as a treatment once a day for a total of three days. QKPCG effectively increased survival and reduced lung injury in treated mice. It significantly reduced the LPS-induced expression of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), IL-1α, and IL-1β. RNA-sequencing followed by real-time quantitative polymerase chain reaction validation suggested a critical role of the secretoglobin family 1A member 1 (Scgb1a1) gene in mediating the protective effect of QKPCG. Further, QKPCG reversed the LPS-induced downregulation of the Clara cell 10 kDa protein (CC10), a pulmonary surfactant protein encoded by Scgb1a1, which is mainly secreted by club cells in the lungs. Exogenous supplementation of CC10 alleviated LPS-induced ALI. Hematoxylin and eosin staining and enzyme-linked immunosorbent assay results further confirmed the anti-inflammatory properties of CC10, which were suggested as mediated via the inhibition of NFκB phosphorylation. In summary, our study provides evidence of the beneficial role of QKPCG in alleviating lung injury, mediated via the decreased disruption of club cells and higher expression of CC10, which leads to NFκB pathway inhibition.

Keywords: LPS; NFκB pathway; acute lung injury; clara cell 10 kDa protein; secretoglobin family 1A member 1 gene.