Re-Du-Ning injection ameliorates LPS-induced lung injury through inhibiting neutrophil extracellular traps formation

Autor: Ling-Dong Kong, Haibo Li, Chenglin Song, Wei Xiao, Wen Lv, Hui Ming Ge, Jiao Qu, Yang Sun, Yitong Liu, Chenxi Yang
Rok vydání: 2021
Předmět:
Lipopolysaccharides
MAPK/ERK pathway
ARDS
medicine.medical_treatment
MAPK
Mitogen-activated protein kinase
ERK1/2
Extracellular signal regulated kinases
i.p
Intraperitoneal injection
Pharmaceutical Science
TNF-α
Tumor necrosis factor α
Pharmacology
GM-CSF
Granulocyte-macrophage Colony Stimulating Factor
Extracellular Traps
Dex
Dexamethasone
Mice
H&E.
Hematoxylin-eosin
0302 clinical medicine
BALF
bronchoalveolar lavage fluid
Drug Discovery
Re-Du-Ning injection
Respiratory system
LPS
Lipopolysaccharide
Lung
0303 health sciences
medicine.diagnostic_test
Blot
ELISA
Enzyme-linked immunosorbent assay
COVID-19
Coronavirus Disease 2019
030220 oncology & carcinogenesis
Molecular Medicine
RDN
Re-Du-Ning injection
Female
PMA
phorbol 12-myristate 13-acetate
IL-1β
Interleukin (IL)-1β
NETs
neutrophil extracellular traps
MPO
Myeloperoxidase
Acute Lung Injury
Intraperitoneal injection
PAD4
peptidyl arginine deiminase 4
Lung injury
Immunofluorescence
Article
cit H3
Citrullinated histone H3
IL-6
Interleukin (IL)-6
03 medical and health sciences
IL-17A
Interleukin (IL)-17A
ARDS
Acute respiratory distress syndrome
medicine
NE
neutrophil elastase
Animals
030304 developmental biology
business.industry
ALI
Acute lung injury
NETs
Neutrophil extracellular traps
medicine.disease
MAPK
Mice
Inbred C57BL
ALI
Complementary and alternative medicine
business
Drugs
Chinese Herbal
Zdroj: Phytomedicine
ISSN: 0944-7113
DOI: 10.1016/j.phymed.2021.153635
Popis: Background Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening diseases and could occur in severe COVID-19 patients. Re-Du-Ning injection (RDN) is a tradition Chinese medicine preparation which has been clinically used for treatment of respiratory diseases including COVID-19. Purpose To elucidate the potential mechanisms of RDN for the treatment of ALI. Methods Female C57BL/6J mice were used to establish ALI model by intraperitoneal injection 10 mg/kg LPS, and RDN injection was intraperitoneally administered with the dose of 5 and 10 mL/kg. The cytokines were measured by ELISA and qPCR. The data related to NETs were analyzed by ELISA, immunofluorescence, Western blotting and network pharmacological approach. Results RDN robustly alleviated LPS-induced ALI. Meanwhile, RDN downregulated the expression of pro-inflammatory cytokines, such as IL-1β, IL-6 and TNF-α. Specifically, RDN treatment inhibited the formation of neutrophil extracellular traps (NETs) and remarkably suppressed the protein of PAD4. The active compound from RDN decreased the phosphorylation of ERK1/2. Conclusion These findings demonstrate that RDN ameliorates LPS-induced ALI through suppressing MAPK pathway to inhibit the formation of NETs.
Graphical abstract Image, graphical abstract
Databáze: OpenAIRE
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