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

作者：Zhenqiao Wei, Rui Gao, Zhen Sun, Wen Yang, Qi He, Chenhui Wang, Jingxiang Zhang, Xiaochang Zhang, Liang Guo, Shengqi Wang · 发表于：Journal of Medical Virology · 年份：2023 · DOI：10.1002/jmv.28790 · 被引用次数：64 · 研究领域：Inflammasome and immune disorders、interferon and immune responses、Cell death mechanisms and regulation

Abstract Baicalin (7‐ d ‐glucuronic acid‐5, 6‐dihydroxyflavone) derived from the root of Scutellaria baicalensis used as Traditional Chinese Medicine (TCM) has been revealed to exert potential antiviral activity via various pathways, while the molecular mechanisms have not been fully understood. Pyroptosis, an inflammatory form of programmed cell death (PCD), is reported to play a crucial role in host cell fate during viral infection. In this study, transcriptome analysis of mice lung tissue reveals that baicalin reverses the alterations of the mRNA levels of PCD‐associated genes upon H1N1 challenge, with a concomitant decrease in the population of H1N1‐induced propidium iodide (PI) + and Annexin Ⅴ + 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 BE...