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

Author:

Peng Wenjun12,Qi Hui3,Zhu Wensi12,Tong Lin12,Rouzi Ainiwaer12,Wu Yuanyuan12ORCID,Han Linxiao12,He Ludan12,Yan Yu12,Pan Ting12,Liu Jie12,Wang Qin12,Jia Zhenhua3,Song Yuanlin245,Zhu Qiaoliang6,Zhou Jian12457ORCID

Affiliation:

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

Abstract

AbstractLHQK 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.

Funder

Science and Technology Commission of Shanghai Municipality

National Natural Science Foundation of China

Publisher

Wiley

Subject

Pulmonary and Respiratory Medicine

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