ArticleBritish journal of pharmacology2021
Bletinib ameliorates neutrophilic inflammation and lung injury by inhibiting Src family kinase phosphorylation and activity.
Article in British journal of pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 51 citations in OpenAlex.
- The role of neutrophils in bronchiectasis.Annals of medicine · 2025Review
- Src Reduces Neutrophil Extracellular Traps Generation and Resolves Acute Organ Damage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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- Targeting Neutrophil-Mediated Inflammation: Identification of Pyrazolidinone Carboxamide Derivatives as Potent Selective Inhibitors of Formyl Peptide Receptor 1 (FPR1)-Activated Neutrophils.ACS pharmacology & translational science · 2025Article
- Drug repurposing of cyclin-dependent kinase inhibitors for neutrophilic acute respiratory distress syndrome and psoriasis.Journal of advanced research · 2025Review
- Advances in acute respiratory distress syndrome: focusing on heterogeneity, pathophysiology, and therapeutic strategies.Signal transduction and targeted therapy · 2025Review
- Ribociclib leverages phosphodiesterase 4 inhibition in the treatment of neutrophilic inflammation and acute respiratory distress syndrome.Journal of advanced research · 2024Article
- RIPK1 inhibitor ameliorates pulmonary injury by modulating the function of neutrophils and vascular endothelial cells.Cell death discovery · 2024Article
- Antimicrobial Activity of Stilbenes fromMicroorganisms · 2023Article
- Bruton's tyrosine kinase is a possible therapeutic target in microscopic polyangiitis.Arthritis research & therapy · 2023Article
- Multiomics reveal human umbilical cord mesenchymal stem cells improving acute lung injuryWorld journal of stem cells · 2023Article
- Chemical Constituents with Anti-Lipid Droplet Accumulation and Anti-Inflammatory Activity fromPlants (Basel, Switzerland) · 2023Article
- GPR84 regulates pulmonary inflammation by modulating neutrophil functions.Acta pharmacologica Sinica · 2023Article
- Upregulation of the protein kinase Lyn is associated with renal injury in type 2 diabetes patients.Renal failure · 2023Article
- Development of genomic phenotype and immunophenotype of acute respiratory distress syndrome using autophagy and metabolism-related genes.Frontiers in immunology · 2023Article
- Pharmacological Mechanism of Sancao Yuyang Decoction in the Treatment of Oral Mucositis Based on Network Pharmacology and Experimental Validation.Drug design, development and therapy · 2023Article
- Ibrutinib Prevents Acute Lung Injury via Multi-Targeting BTK, FLT3 and EGFR in Mice.International journal of molecular sciences · 2022Article
- Exploring the Anti-inflammatory Effects of Protopine Total Alkaloids ofFrontiers in veterinary science · 2022Article
- Bioinformatics analysis of potential pathogenesis and risk genes of immunoinflammation-promoted renal injury in severe COVID-19.Frontiers in immunology · 2022Article
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeNeutrophil overactivation is crucial in the pathogenesis of acute lung injury (ALI). Bletinib (3,3'-dihydroxy-2',6'-bis(p-hydroxybenzyl)-5-methoxybibenzyl), a natural bibenzyl, extracted from the Bletilla plant, exhibits anti-inflammatory, antibacterial, and antimitotic effects. In this study, we evaluated the therapeutic effects of bletinib in human neutrophilic inflammation and LPS-mediated ALI in mice. EXPERIMENTAL APPROACH: In human neutrophils activated with the formyl peptide (fMLP), we assessed integrin expression, superoxide anion production, degranulation, neutrophil extracellular trap (NET) formation, and adhesion through flow cytometry, spectrophotometry, and immunofluorescence microscopy. Immunoblotting was used to measure phosphorylation of Src family kinases (SFKs) and downstream proteins. Finally, a LPS-induced ALI model in male BALB/c mice was used to investigate the potential therapeutic effects of bletinib treatment. KEY
resultsIn activated human neutrophils, bletinib reduced degranulation, respiratory burst, NET formation, adhesion, migration, and integrin expression; suppressed the enzymic activity of SFKs, including Src, Lyn, Fgr, and Hck; and inhibited the phosphorylation of SFKs as well as Vav and Bruton's tyrosine kinase (Btk). In mice with ALI, the pulmonary sections demonstrated considerable amelioration of prominent inflammatory changes, such as haemorrhage, pulmonary oedema, and neutrophil infiltration, after bletinib treatment. CONCLUSION AND IMPLICATIONS: Bletinib regulates neutrophilic inflammation by inhibiting the SFK-Btk-Vav pathway. Bletinib ameliorates LPS-induced ALI in mice. Further biochemical optimisation of bletinib may be a promising strategy for the development of novel therapeutic agents for inflammatory diseases.
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