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A previous study showed that berberine (BBR) significantly ameliorated the pulmonary inflammation in mice with influenza viral pneumonia but its underlying mechanism is not entirely understood. In this study, we reproduced the mouse model of influenza viral pneumonia through intranasal infection of A\/Puerto Rico\/8\/34 (H1N1), to further investigate the anti\u2010inflammatory mechanism of BBR based on nucleotide\u2010binding oligomerization domain\u2010like receptor protein (NLRP) 3 inflammasome activation and Gasdermin D (GSDMD)\u2010mediated pyroptosis. Consistent with MCC950 (10\u2009mg\/kg, a specific NLRP3 inflammasome inhibitor), BBR (10\u2009mg\/kg) obviously improved the weight loss and survival rate of infected mice, alleviated their pulmonary inflammation, and suppressed the accumulation of tumor necrosis factor and interleukin (IL)\u20106 in lungs without obvious inhibition on viral multiplication (hemagglutinin titer and nucleoprotein messenger RNA). Moreover, BBR (10\u2009mg\/kg) reduced the expressions of NLRP3, apoptosis\u2010associated speck\u2010like protein containing a CARD (ASC), and cysteinyl aspartate\u2010specific proteinase (Caspase)1 (Caspase1 precursor [Pro\u2010caspase1]\u2009+\u2009Caspase1p20 subunit) and the ratio of Caspase1p20 subunit to Caspase1, thus inhibiting the NLRP3 inflammasome activation and resulting in the decreased contents of mature IL\u20101\u03b2 and IL\u201018 in lungs. The GSDMD expression (GSDMD precursor [Pro\u2010GSDMD]\u2009+\u2009GSDMD\u2010N terminal [NT]) and the ratio of GSDMD\u2010NT to GSDMD were also declined by BBR (10\u2009mg\/kg). These evidence indicate that BBR may ameliorate pulmonary inflammation in mice with influenza viral pneumonia through inhibiting NLRP3 inflammasome activation, as well as depressing GSDMD\u2010mediated pyroptosis via declining GSDMD expression and restraining NLRP3 inflammasome\u2010mediated GSDMD activation.<\/jats:p>","DOI":"10.1002\/ddr.21995","type":"journal-article","created":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T14:03:27Z","timestamp":1663337007000},"page":"1707-1721","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Berberine ameliorates pulmonary inflammation in mice with influenza viral pneumonia by inhibiting NLRP3 inflammasome activation and gasdermin D\u2010mediated pyroptosis"],"prefix":"10.1002","volume":"83","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8543-9543","authenticated-orcid":false,"given":"Chen","family":"An","sequence":"first","affiliation":[{"name":"Department of 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