MNK as a potential pharmacological target for suppressing LPS-induced acute lung injury in mice

Gao, Jianfeng; Teng, Li; Yang, Shaofeng; Huang, Shuguang; Li, Linrui; Zhou, Li; Liu, Guoquan; Tang, Hongliang

doi:10.1016/j.bcp.2021.114499

Cited by 14 publications

(8 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We confirmed that this LDH level is comparable to the LDH level after the intranasal treatment of lipopolysaccharide (Fig. S1), which is generally used to induce lung injury ( 30 , 31 ). In addition, we observed massive neutrophil infiltration in the lungs 24 h after the Mp challenge using hematoxylin and eosin (H&E) staining ( Fig.…”

Section: Resultssupporting

confidence: 82%

Neutrophil-Mediated Lung Injury Both via TLR2-Dependent Production of IL-1α and IL-12 p40, and TLR2-Independent CARDS Toxin after Mycoplasma pneumoniae Infection in Mice

et al. 2021

View full text Add to dashboard Cite

show abstract

Section: Resultssupporting

confidence: 82%

Neutrophil-Mediated Lung Injury Both via TLR2-Dependent Production of IL-1α and IL-12 p40, and TLR2-Independent CARDS Toxin after Mycoplasma pneumoniae Infection in Mice

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Severe lung infection, pulmonary contusion, and pulmonary embolism are the direct causes of ALI ( He et al, 2021 ). The main pathological features are acute inflammation and apoptosis of alveolar epithelial cells ( Allen and Kurdowska, 2014 ; Liu et al, 2020 ; Gao et al, 2021 ).…”

Section: The Protection Of Ba Against Respiratory Diseasesmentioning

confidence: 99%

The protective effects of baicalin for respiratory diseases: an update and future perspectives

Song

Liu

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

Background: Respiratory diseases are common and frequent diseases. Due to the high pathogenicity and side effects of respiratory diseases, the discovery of new strategies for drug treatment is a hot area of research. Scutellaria baicalensis Georgi (SBG) has been used as a medicinal herb in China for over 2000 years. Baicalin (BA) is a flavonoid active ingredient extracted from SBG that BA has been found to exert various pharmacological effects against respiratory diseases. However, there is no comprehensive review of the mechanism of the effects of BA in treating respiratory diseases. This review aims to summarize the current pharmacokinetics of BA, baicalin-loaded nano-delivery system, and its molecular mechanisms and therapeutical effects for treating respiratory diseases.Method: This review reviewed databases such as PubMed, NCBI, and Web of Science from their inception to 13 December 2022, in which literature was related to “baicalin”, “Scutellaria baicalensis Georgi”, “COVID-19”, “acute lung injury”, “pulmonary arterial hypertension”, “asthma”, “chronic obstructive pulmonary disease”, “pulmonary fibrosis”, “lung cancer”, “pharmacokinetics”, “liposomes”, “nano-emulsions”, “micelles”, “phospholipid complexes”, “solid dispersions”, “inclusion complexes”, and other terms.Result: The pharmacokinetics of BA involves mainly gastrointestinal hydrolysis, the enteroglycoside cycle, multiple metabolic pathways, and excretion in bile and urine. Due to the poor bioavailability and solubility of BA, liposomes, nano-emulsions, micelles, phospholipid complexes, solid dispersions, and inclusion complexes of BA have been developed to improve its bioavailability, lung targeting, and solubility. BA exerts potent effects mainly by mediating upstream oxidative stress, inflammation, apoptosis, and immune response pathways. It regulates are the NF-κB, PI3K/AKT, TGF-β/Smad, Nrf2/HO-1, and ERK/GSK3β pathways.Conclusion: This review presents comprehensive information on BA about pharmacokinetics, baicalin-loaded nano-delivery system, and its therapeutic effects and potential pharmacological mechanisms in respiratory diseases. The available studies suggest that BA has excellent possible treatment of respiratory diseases and is worthy of further investigation and development.

show abstract

“…19,20 In a mouse model of LPS-induced acute lung injury, MNK2 knockout resulted in reduced lung histopathological changes, decreased neutrophil counts, and diminished production of IL-6, TNF-α, and keratinocyte-derived chemoattractants in mouse bronchoalveolar lavage fluid. 21 In human keratinocytes, inhibition to MNK1 and the abolishment of eIF4E phosphorylation decrease the anisomycin-induced protein release of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6. 22 Furthermore, it has been proved that suppression of MNK2 in tumor-associated macrophages reprogrammed antiinflammatory macrophages toward a proinflammatory phenotype with the ability to activate CD8+ T cells that can resist tumor development.…”

Section: ■ Introductionmentioning

confidence: 99%

Discovery of D25, a Potent and Selective MNK Inhibitor for Sepsis-Associated Acute Spleen Injury

Li,

Ke,

et al. 2024

J. Med. Chem.

View full text Add to dashboard Cite

Mitogen-activated protein kinase-interacting protein kinases (MNKs) and phosphorylate eukaryotic initiation factor 4E (p-eIF4E) play a critical role in regulating mRNA translation and protein synthesis associated with the development of cancer, metabolism, and inflammation. This study undertakes the modification of a 4-(3-(piperidin-4-yl)-1H-pyrazol-5-yl)pyridine structure, leading to the discovery of 4-(3-(piperidin-4-yl)-1H-pyrazol-5-yl)-1H-pyrrolo[2,3-b]pyridine (D25) as a potent and selective MNK inhibitor. D25 demonstrated inhibitory activity, with IC 50 values of 120.6 nM for MNK1 and 134.7 nM for MNK2, showing exceptional selectivity. D25 inhibited the expression of pro-inflammation cytokines in RAW264.7 cells, such as inducible NO synthase, cyclooxygenase-2, and interleukin-6 (IL -6). In the lipopolysaccharide-induced sepsis mouse model, D25 significantly reduced p-eIF4E in spleen tissue and decreased the expression of tumor necrosis factor α, interleukin-1β, and IL-6, and it also reduced the production of reactive oxygen species, resulting in improved organ injury caused by inflammation. This suggests that D25 may provide a potential treatment for sepsis and sepsis-associated acute spleen injury.

show abstract

MNK as a potential pharmacological target for suppressing LPS-induced acute lung injury in mice

Abstract: Graphical abstract

Cited by 14 publications

References 40 publications

Neutrophil-Mediated Lung Injury Both via TLR2-Dependent Production of IL-1α and IL-12 p40, and TLR2-Independent CARDS Toxin after Mycoplasma pneumoniae Infection in Mice

Neutrophil-Mediated Lung Injury Both via TLR2-Dependent Production of IL-1α and IL-12 p40, and TLR2-Independent CARDS Toxin after Mycoplasma pneumoniae Infection in Mice

The protective effects of baicalin for respiratory diseases: an update and future perspectives

Discovery of D25, a Potent and Selective MNK Inhibitor for Sepsis-Associated Acute Spleen Injury

Contact Info

Product

Resources

About