Xuanqing Hefa formula relieves sepsis-triggered acute lung injury by targeting the NLRP3/Caspase-1 pyroptosis mechanism.

Introduction: Acute lung injury (ALI), frequently triggered by sepsis, is characterized by severe respiratory distress and high mortality, particularly in critically ill or elderly individuals. Xuanqing Hefa formula (XQHF) has been clinically applied to alleviate ALI by reducing pulmonary inflammation; however, its underlying mechanisms remain poorly understood. This study aimed to evaluate the therapeutic effects of XQHF on sepsis-induced ALI using both Materials and methods: Multiple active constituents of XQHF were identified using UPLC-MS/MS. To investigate the therapeutic potential of XQHF against sepsis-induced lung injury, a cecal ligation and puncture (CLP) model was established in mice, while an Results: The results demonstrated that XQHF significantly preserved lung tissue architecture by attenuating both inflammatory responses and oxidative stress, thereby improving the survival rate of septic mice. At the molecular level, XQHF inhibited the expression of key pyroptosis-related proteins. Similar protective effects were observed in the LPS + Nigericin-induced pyroptosis model in iBMDMs, where XQHF also reduced apoptosis. Confocal microscopy further confirmed that XQHF markedly decreased the expression of pro-inflammatory cytokines, including IL-1β and IL-18. Conclusions: Our results suggest that the therapeutic effects of XQHF may be attributed to the synergistic actions of its multiple active constituents, which collectively suppress the inflammatory cascade and attenuate pyroptosis, thereby alleviating lung injury. Furthermore, both