Quercetin protects against LPS-induced lung injury in mice via SIRT1-mediated suppression of PKM2 nuclear accumulation

• DOI: 10.1016/j.ejphar.2022.175352
• Publication Date: 2022-10-26T15:20:41Z
• Authors: Ling-li Chen; Chao Song; Yan Zhang; Yi Li; Yu-hao Zhao; Feng-yu Lin; Duo-duo Han; Min-hui Dai; Wen Li; Pin-hua Pan
• Keywords: Pyroptosis

The role of NOD-like receptor protein 3 (NLRP3)-mediated macrophages pyroptosis in acute lung injury (ALI) is well-established. Quercetin (Que) a natural bioflavonoid compound with anti-inflammatory and antioxidative properties that reportedly inhibits the NLRP3 inflammasome sepsis-induced organ dysfunctions such as ALI. However, mechanism underlying inhibitory effect quercetin on activation remains unclear. In this study, we established an endotoxin-induced ALI mouse model vitro LPS challenge. We demonstrated administration could significantly reduce pulmonary decrease production pro-inflammatory cytokines. Moreover, found inhibit by suppressing nuclear accumulation PKM2 increasing SIRT1 levels. Importantly, treatment SRT1720 (a specific activator) NLRP3. Besides, preventing dimerization ML265 yielded effect, similar to findings observed for SRT1720. addition, silencing or inhibition EX527 increase override quercetin-mediated activity. These indicated downregulate inhibiting upregulating expression, expanding landscape ARDS.