Dihydrotanshinone Alleviates Lipopolysaccharide‐Induced Acute Lung Injury by Targeting NEK7 to Inhibit NLRP3 Inflammasome Activation

ABSTRACT Acute lung injury (ALI) carries high mortality with limited treatment options. Dihydrotanshinone (DHT), a bioactive component of Radix Salviae Miltiorrhizae , exhibits anti‐inflammatory properties, though its molecular targets remain unclear. Given the critical role of NIMA‐related kinase 7 (NEK7)‐mediated NOD‐like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation in inflammatory diseases, this study investigated DHT's anti‐inflammatory effects through NEK7–NLRP3 regulation. In vitro, lipopolysaccharide (LPS) + ATP‐stimulated macrophages were used to activate the NLRP3 inflammasome. In vivo, ALI was induced in BALB/c mice via intratracheal LPS instillation (4 mg/kg). NEK7 knockdown was achieved through intravenous and intranasal delivery of NEK7 siRNA. Protein expression of NEK7–NLRP3 components was analyzed in both models. Results indicated that LPS + ATP stimulation significantly upregulated NEK7‐NLRP3 inflammasome components (NEK7, NLRP3, c‐caspase‐1, c‐IL‐1β) in macrophages and ALI tissues. DHT inhibited NEK7‐NLRP3 complex formation, suppressing inflammasome assembly and activation. NEK7 knockdown eliminated IL‐1β secretion in vitro and alleviated ALI in vivo. DHT treatment prevented pulmonary injury and reduced neutrophil infiltration. This study identifies DHT as a novel NEK7‐NLRP3 inflammasome inhibitor, demonstrating its therapeutic potential for ALI treatment. These findings provide a new pharmacological approach targeting NEK7‐mediated inflammasome activation in inflammatory lung diseases.