FIGURE 8.

Proposed model of the effect of koumine (KM) on reactive oxygen species (ROS)/NF-κB/nod-like receptor NOD-like receptor protein 3 (NLRP3) signaling. The NLRP3 inflammasome can be activated by multiple stimuli. The priming step or “signal 1” is mediated by TLR agonists such as LPS, which results in NF-κB-dependent upregulation of NLRP3 and pro-IL-1β expression. The assembly step or “signal 2” mediated by stimulation with numerous pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs), such as ATP, nigericin and MSU, promotes ASC oligomerization, leading to activation of the NLRP3 inflammasome complex. The stimulation of cells with LPS, ATP, nigericin or MSU leads to ROS production and activates both the priming and assembly steps, which ultimately leads to NLRP3 inflammasome activation. The activated NLRP3 inflammasome then cleaves pro-caspase-1 into activated caspase-1 and thereby promotes mature IL-1β secretion. KM inhibits NLRP3 inflammasome activation associated with regulating the ROS/NF-κB/NLRP3 pathway and consequently suppresses IL-1β production.