Lianhua Qingke ameliorates lipopolysaccharide-induced lung injury by inhibiting neutrophil extracellular traps formation and pyroptosis

Wenjun Peng; Hui Qi; Wensi Zhu; Lin Tong; Ainiwaer Rouzi; Yuanyuan Wu; Linxiao Han; Ludan He; Yu Yan; Ting Pan; Jie Liu; Qin Wang; Zhenhua Jia; Yuanlin Song; Qiaoliang Zhu; Jian Zhou

doi:10.1002/pul2.12295

Lianhua Qingke ameliorates lipopolysaccharide-induced lung injury by inhibiting neutrophil extracellular traps formation and pyroptosis

Pulm Circ. 2023 Oct 6;13(4):e12295. doi: 10.1002/pul2.12295. eCollection 2023 Oct.

Authors

Wenjun Peng^{1

2}, Hui Qi³, Wensi Zhu^{1

2}, Lin Tong^{1

2}, Ainiwaer Rouzi^{1

2}, Yuanyuan Wu^{1

2}, Linxiao Han^{1

2}, Ludan He^{1

2}, Yu Yan^{1

2}, Ting Pan^{1

2}, Jie Liu^{1

2}, Qin Wang^{1

2}, Zhenhua Jia³, Yuanlin Song^{2

4

5}, Qiaoliang Zhu⁶, Jian Zhou^{1

2

4

5

7

8}

Affiliations

¹ Department of Pulmonary and Critical Care Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital Fudan University Shanghai China.
² Shanghai Key Laboratory of Lung Inflammation and Injury Shanghai China.
³ Hebei Academy of Integrated Traditional Chinese and Western Medicine Hebei Shijiazhuang China.
⁴ Shanghai Institute of Infectious Disease and Biosecurity Fudan University Shanghai China.
⁵ Research Center for Chemical Injury, Emergency and Critical Medicine of Fudan University Fudan University Shanghai China.
⁶ Department of Thoracic Surgery, Zhongshan Hospital Fudan University Shanghai China.
⁷ Key Laboratory of Chemical Injury, Emergency and Critical Medicine of Shanghai Municipal Health Commission Fudan University Shanghai China.
⁸ Center of Emergency and Critical Medicine in Jinshan Hospital of Fudan University Fudan University Shanghai China.

Abstract

LHQK is a patented Traditional Chinese Medicine (TCM) which is clinically used for acute tracheobronchitis, cough, and other respiratory diseases. Recent studies have proved that LHQK exhibits excellent clinical efficacy in the treatment of acute lung injury (ALI). However, the corresponding mechanisms remain largely unexplored. In this study, we investigated the effects and the underlying mechanisms of LHQK on lipopolysaccharide (LPS)-induced ALI in mice. The pathological examination, inflammatory cytokines assessments, and mucus secretion evaluation indicated that administration of LHQK ameliorated LPS-induced lung injury, and suppressed the secretion of Muc5AC and pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β) in plasma and BALF. Furthermore, the results of cell-free DNA level showed that LHQK significantly inhibited LPS-induced NETs formation. Western blot revealed that LHQK effectively inhibited LPS-triggered pyroptosis in the lung. In addition, RNA-Seq data analysis, relatively bioinformatic analysis, and network pharmacology analysis revealed that LHQK and relative components may play multiple protective functions in LPS-induced ALI/acute respiratory distress syndrome (ARDS) by regulating multiple targets directly or indirectly related to NETs and pyroptosis. In conclusion, LHQK can effectively attenuate lung injury and reduce lung inflammation by inhibiting LPS-induced NETs formation and pyroptosis, which may be regulated directly or indirectly by active compounds of LHQK.

Keywords: Traditional Chinese Medicine (TCM); acute respiratory distress syndrome (ARDS); pulmonary inflamation.