Jatrorrhizine Suppresses Murine-Norovirus-Triggered N-GSDMD-Dependent Pyroptosis in RAW264.7 Macrophages

药根碱抑制小鼠诺如病毒引发的 RAW264.7 巨噬细胞中 N-GSDMD 依赖性细胞焦亡

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作者:Ming Fu, Nini Chen, Yanhe Zhou, Sidong Chen, Wanfu Xu, Sitang Gong, Lanlan Geng

Abstract

Human norovirus (HNV) is one of the emerging and rapidly spreading groups of pathogens and the main cause of epidemic viral gastroenteritis globally. Due to a lack of in vitro culture systems and suitable animal models for HNV infection, murine norovirus (MNV) has become a common model. A recent study showed that MNV activates NLRP3 inflammasome leading to pyroptosis. Jatrorrhizine (JAT) is a natural isoquinoline alkaloid isolated from Coptis Chinensis, which has been proven to have antibacterial, anti-inflammatory, and antitumor effects. However, whether JAT has an effect on norovirus gastroenteritis and the underlying molecular mechanism remain unclear. Here, we found that JAT could ameliorate NLRP3-N-GSDMD-dependent pyroptosis induced by MNV infection through inhibiting the MAPKs/NF-κB signaling pathways and decrease MNV replication in RAW264.7 macrophages, suggesting that JAT has the potential to be a therapeutic agent for treating norovirus gastroenteritis.

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