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. 2024 Dec 13;29(24):5900. doi: 10.3390/molecules29245900

Figure 5.

Figure 5

Graphical summary of quercetin-mediated anti-inflammatory action through targeting caspase-11 noncanonical inflammasome in macrophages. Pro-caspase-11 senses intracellular LPS through direct interaction, forming LPS-pro-caspase-11 complexes, which then undergo oligomerization to generate the caspase-11 non-canonical inflammasome. The caspase-11 noncanonnical inflammasome is activate by the autoproteolysis of caspase-11, leading to: (1) the proteolytic activation of GSDMD and GSDMD pore-induced pyroptosis, (2) iNOS-catalyzed NO production, and (3) the caspase-1-mediated proteolytic maturation and release of pro-inflammatory cytokines through the GSDMD pores in macrophages. Quercetin inhibits the autoproteolytic activation of the caspase-11 noncanonical inflammasome (red box), leading to the suppression of pyroptosis and the release of pro-inflammatory cytokines and NO in macrophages. Additionally, it ameliorates LPS-induced acute lethal sepsis in mice. Black arrows indicate the activation pathways.