Qinbaohong Zhike Oral Liquid Attenuates LPS-Induced Acute Lung Injury in Immature Rats by Inhibiting OLFM4

Abstract

Acute respiratory infections (ARIs) are a common public safety threat with high morbidity and mortality in pediatric patients worldwide. Qinbaohong Zhike oral liquid (QBH), a marketed traditional Chinese medicine product, has been widely used to cure respiratory diseases. QBH is reported to have antitussive, expectorant, and antiasthmatic properties. However, its treatment effect against ARIs is not elucidated. This study aimed to explore the therapeutic efficacy of QBH in the treatment of ARIs-induced pneumonia. Network pharmacology was used to predict the possible targets of QBH against ARIs. Next, the tracheal lipopolysaccharide (LPS-)-induced acute lung injury (ALI) immature rat model was constructed to evaluate the therapeutic effect of QBH. Tandem mass tag (TMT-)-based quantitative proteomics was then used to screen the in-depth disease targets of QBH. QBH exerted a protective effect against LPS-induced ALI by inhibiting pulmonary pathological damage. QBH also reduced the levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and granulocyte macrophage colony-stimulating factor (GM-CSF) in the serum and IL-1β, IL-6, IL-8, TNF-α, IFN-γ, and GM-CSF in the lung tissue. Based on proteomic data, olfactomedin 4 (OLFM4) related to immunity and inflammation was selected as a potential target. Western blot analysis further confirmed the moderating effect of QBH downregulation on OLFM4 in the lung tissue. Our findings demonstrated that QBH alleviated lung tissue damage and inflammatory reaction via inhibiting OLFM4 expression in LPS-challenged immature rats. Our research indicates that QBH may have therapeutic potential for treating ARIs-related ALI in pediatric patients, which also serves as a candidate target for drug therapy of ALI by intervening OLFM-related signaling pathways.

Combination of transcriptional biomarkers and clinical parameters for early prediction of sepsis indued acute respiratory distress syndrome

“…OLFM4, an important regulator of inflammatory and immune responses, is highly expressed in various inflammatory diseases ( 17 ). In an LPS-challenge rat model, blockage of OLFM4 expression was confirmed to mitigate lung tissue damage and hyperinflammatory response ( 18 ). Additionally, Higher percentages of OLFM4 + neutrophils were shown to be associated with worsening clinical outcomes in patients with sepsis, blunt traumatic injuries, and ARDS ( 19 , 20 ).…”

Downregulation of ROR2 attenuates LPS‐induced A549 cell injury through JNK and ERK signaling pathways

“…It has been reported that TNF‐α, IL‐1β, and IL‐8 are important pro‐inflammatory mediators in inflammatory responses, moreover, excessive release of the pro‐inflammatory cytokines play crucial roles in the pathogenesis and development of ALI. 21 , 22 , 23 CCNB1 and CDC2 are known to be important cell cycle regulatory proteins, and play key roles in promoting cell cycle progression. 24 , 25 Caspases, especially caspase‐3 and caspase‐9, are considered as crucial effectors of cell apoptosis.…”

“…Cell proliferation assay by CCK‐8 as well as cell cycle and cell apoptosis analysis by flow cytometry showed that LPS administration significantly decreased cell proliferation, resulted in cell cycle arrest at G1 phage, and elevated apoptosis rate of A549 cells. It has been reported that TNF‐α, IL‐1β, and IL‐8 are important pro‐inflammatory mediators in inflammatory responses, moreover, excessive release of the pro‐inflammatory cytokines play crucial roles in the pathogenesis and development of ALI 21–23 . CCNB1 and CDC2 are known to be important cell cycle regulatory proteins, and play key roles in promoting cell cycle progression 24,25 .…”