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Growing evidence shows that the overproduction of reactive oxygen species and granular proteolytic enzymes from activated neutrophils is linked to the pathogenesis of acute inflammatory diseases. However, adequate therapeutic targets are still lacking to regulate neutrophil functions. Herein, we report that MVBR\u201028, synthesized from the Mannich bases of heterocyclic chalcone, has anti\u2010neutrophilic inflammatory effects through regulation of intracellular pH. MVBR\u201028 modulates neutrophil functions by attenuating respiratory burst, degranulation, and migration. Conversely, MVBR\u201028 has no antioxidant effects and fails to alter elastase activity in cell\u2010free systems. The anti\u2010inflammatory effects of MVBR\u201028 are not seen through cAMP pathways. Significantly, MVBR\u201028 potently inhibits extracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx in\n                    <jats:italic>N<\/jats:italic>\n                    \u2010formyl\u2010methionyl\u2010leucyl\u2010phenylalanine (fMLF)\u2010 and thapsigargin\u2010activated human neutrophils. Notably, MVBR\u201028 attenuates fMLF\u2010induced intracellular alkalization in a K\n                    <jats:sup>+<\/jats:sup>\n                    \u2010dependent manner, which is upstream of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    pathways. Collectively, these findings provide new insight into Mannich bases of heterocyclic chalcone regarding the regulation of neutrophil functions and the potential for the development of MVBR\u201028 as a lead compound for treating neutrophilic inflammatory diseases.\n                  <\/jats:p>","DOI":"10.1096\/fj.201903123r","type":"journal-article","created":{"date-parts":[[2020,4,10]],"date-time":"2020-04-10T08:29:33Z","timestamp":1586507373000},"page":"7127-7143","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A synthesized heterocyclic chalcone inhibits neutrophilic inflammation through K\n                    <sup>+<\/sup>\n                    \u2010dependent pH regulation"],"prefix":"10.1096","volume":"34","author":[{"given":"Shun\u2010Chin","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Taipei Veterans General Hospital and National Yang\u2010Ming University Taipei Taiwan"},{"name":"Graduate Institute of Natural Products, College of Medicine Chang Gung University Taoyuan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi\u2010Hsuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Natural Products, College of Medicine Chang Gung University Taoyuan Taiwan"},{"name":"Division of Natural Products, Graduate Institute of Biomedical Sciences, College of Medicine Chang Gung University Taoyuan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yung\u2010Fong","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Chang Gung Memorial Hospital Taoyuan Taiwan"},{"name":"Graduate Institute of Clinical Medical Sciences, College of Medicine Chang Gung University Taoyuan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya\u2010Wen","family":"Chang","sequence":"additional","affiliation":[{"name":"Graduate Institute of 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