Scutellarin inhibits caspase-11 activation and pyroptosis in macrophages via regulating PKA signaling

• DOI: 10.1016/j.apsb.2020.07.014
• Publication Date: 2020-07-31T07:29:18Z
• Authors: Jiezhou Ye; Bo Zeng; Meiyan Zhong; Hongchun Li; Lihui Xu; Junxiang Shu; Yaofeng Wang; Fan Yang; Chunsu Zhong; Xunjia Ye; Xianhui He; Dongyun Ouyang
• Keywords: Pyroptosis; Scutellarin; NALP3

Inflammatory caspase-11 senses and is activated by intracellular lipopolysaccharide (LPS) leading to pyroptosis that has critical role in defensing against bacterial infection, whereas its excess activation under pathogenic circumstances may cause various inflammatory diseases. However, there are few known drugs can control activation. We report here scutellarin, a flavonoid from Erigeron breviscapus, acted as an inhibitor for macrophages. Scutellarin dose-dependently inhibited LPS-induced release of caspase-11p26 (indicative activation) generation N-terminal fragment gasdermin D (GSDMD-NT), reduced pyroptosis. It also suppressed the non-canonical nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome evidenced apoptosis-associated speck-like protein CARD (ASC) speck formation decreased interleukin-1 beta (IL-1β) caspase-1p10 secretion, NLRP3-specific MCC950 only IL-1β ASC but not RAW 264.7 cells lacking expression. Moreover, scutellarin treatment increased Ser/Thr phosphorylation at kinase A (PKA)-specific sites, inhibitory action on was largely abrogated PKA H89 or adenylyl cyclase MDL12330A. Collectively, our data indicate macrophages least partly via regulating signaling pathway.