Pinostrobin targets NLRP3 assembly for treatment of NLRP3-associated inflammatory diseases

The aberrant activation of the NLRP3 inflammasome is implicated in the pathogenesis of various human inflammation-related diseases. Through both pharmacological and molecular approaches, we demonstrated that pinostrobin effectively inhibits the activation of the NLRP3 inflammasome in bone marrow-derived macrophages (BMDMs), without affecting the activation of NLRC4 or AIM2 inflammasomes. Pinostrobin achieves this by reducing the ubiquitination level of NLRP3 through the scavenging of intracellular reactive oxygen species (ROS), thereby blocking the assembly process of the NLRP3 inflammasome. Importantly, pinostrobin was shown to alleviate both canonical and non-canonical NLRP3 inflammasome-mediated inflammatory diseases in mice. Our findings highlight pinostrobin as a promising and novel agent for developing NLRP3 inhibitors to combat NLRP3-driven diseases and provide an effective tool for pharmacologically investigating NLRP3 biology.