Baicalin inhibits influenza A (H1N1)‐induced pyroptosis of lung alveolar epithelial cells via caspase‐3/GSDME pathway

cells. Intriguingly, we find that baicalin contributes to the survival of infected lung alveolar epithelial cells partly through its inhibition of H1N1-induced cell pyroptosis, which is manifested by reduced bubble-like protrusion cells and lactate dehydrogenase (LDH) release. Moreover, the antipyroptosis effect of baicalin in response to H1N1 infection is found to be mediated by its repression on caspase-3/Gasdermin E (GSDME) pathway. Cleaved caspase-3 and N-terminal fragment of GSDME (GSDME-N) are detected in H1N1-infected cell lines and mice lung tissues, which are markedly reversed by baicalin treatment. Furthermore, inhibition of caspase-3/GSDME pathway by caspase-3 inhibitor or siRNA exerts an antipyroptosis effect equal to that of baicalin treatment in infected A549 and BEAS-2B cells, indicating a pivotal role of caspase-3 in the antiviral activities of baicalin. Conclusively, for the first time, we demonstrate that baicalin could effectively suppress H1N1-induced pyroptosis of lung alveolar epithelial cells via caspase-3/GSDME pathway both in vitro and in vivo.