Figure 9.

Schematic diagram illustrating the inhibitory effect of curcumin on microglial pyroptosis and proinflammatory responses by NF-κB signaling suppression and NLRP3 inhibition after stroke. Ischemic stroke triggers the activation of NF-κB with the translocation of p50 and p65 into the nucleus in microglia, facilitating the transcription of target genes, such as GSDMD, NLRP3, IL-1β, and IL-18. The oligomerization of NLRP3 with the ASC and pro-caspase-1 generates NLRP3 inflammasome, which activates caspase-1. Activated caspase-1 subsequently cleaves the GSDMD, pro-IL-1β, and pro-IL-18 into GSDMD-N, IL-1β, and IL-18, respectively. GSDMD-N translocates to the plasma membrane and eventually forms membrane pores, leading to the release of IL-1β and IL-18. Thus, the microglial pyroptosis-mediated proinflammatory responses aggravate stroke-induced white matter damage. Curcumin dramatically suppresses NF-κB signaling, inhibiting stroke-triggered NLRP3 upregulation and activation and microglial pyroptosis. Consequently, brain inflammation is significantly decreased, reversing white matter damage and function deficits.