Quercetin protects against LPS-induced lung injury in mice via SIRT1-mediated suppression of PKM2 nuclear accumulation
The function of NOD-like receptor protein 3 (NLRP3)-mediated macrophages pyroptosis in acute lung injuries (ALI) is well-established. Quercetin (Que) is really a natural bioflavonoid compound with anti-inflammatory and antioxidative qualities that apparently inhibits the NLRP3 inflammasome in sepsis-caused organ dysfunctions for example ALI. However, the mechanism underlying the inhibitory aftereffect of quercetin on NLRP3 activation remains unclear. Within this study, we established an endotoxin-caused ALI mouse model by having an in vitro LPS challenge. We shown the administration of quercetin could considerably reduce lung injuries and reduce producing pro-inflammatory cytokines. Furthermore, we discovered that quercetin could hinder the activation from the NLRP3 inflammasome by suppressing the nuclear accumulation of PKM2 and growing SIRT1 levels. Importantly, treatment with SRT1720 (a particular SIRT1 activator) could hinder the nuclear accumulation of PKM2 and also the activation of NLRP3. Besides, stopping PKM2 dimerization with ML265 produced an anti-inflammatory effect, much like findings observed for SRT1720. Additionally, we discovered that SIRT1 silencing or inhibition by EX527 could increase NLRP3 activation and nuclear accumulation of PKM2 and override quercetin-mediated anti-inflammatory activity. These bits of information established that quercetin could downregulate NLRP3 inflammasome activation by inhibiting the nuclear accumulation of PKM2 and upregulating SIRT1 expression, expanding the therapy landscape for ARDS.