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Bletinib (3,3\u2032\u2010dihydroxy\u20102\u2032,6\u2032\u2010bis(\n                      <jats:italic>p<\/jats:italic>\n                      \u2010hydroxybenzyl)\u20105\u2010methoxybibenzyl), a natural bibenzyl, extracted from the\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Bletilla<\/jats:italic>\n                      <\/jats:styled-content>\n                      plant, exhibits anti\u2010inflammatory, antibacterial, and antimitotic effects. In this study, we evaluated the therapeutic effects of bletinib in human neutrophilic inflammation and LPS\u2010mediated ALI in mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>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\u2010induced ALI model in male BALB\/c mice was used to investigate the potential therapeutic effects of bletinib treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>In 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>Bletinib regulates neutrophilic inflammation by inhibiting the SFK\u2010Btk\u2010Vav pathway. Bletinib ameliorates LPS\u2010induced ALI in mice. Further biochemical optimisation of bletinib may be a promising strategy for the development of novel therapeutic agents for inflammatory diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.15597","type":"journal-article","created":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T01:10:20Z","timestamp":1623805820000},"page":"4069-4084","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Bletinib ameliorates neutrophilic inflammation and lung injury by inhibiting Src family kinase phosphorylation and activity"],"prefix":"10.1111","volume":"178","author":[{"given":"Ting\u2010I","family":"Kao","sequence":"first","affiliation":[{"name":"Graduate Institute of Biomedical Sciences and Graduate Institute of Natural Products, College of Medicine Chang Gung University  Taoyuan Taiwan"},{"name":"Division of Chinese Internal Medicine, Department of Traditional Chinese Medicine Chang Gung Memorial Hospital  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