Xuebijing inhibits alveolar macrophage M1 polarization by regulating ROS-mediated NLRP3 inflammasome signaling

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are devastating acute pulmonary conditions with high mortality rates and limited effective treatment options. This study aimed to investigate the therapeutic potential of XBJ on ALI and its potential mechanism.

We developed an in vitro model of lipopolysaccharide (LPS)-induced ALI and evaluated the effects of XBJ pre-treatment on oxidative stress, inflammatory responses, and the polarization state of alveolar macrophages.

LPS exposure significantly elevated the levels of reactive oxygen species (ROS) and oxidants 8-hydroxy-2'-deoxyguanosine (8-OHDG) and malondialdehyde (MDA) in alveolar macrophages. It also elevated the concentrations of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-23. XBJ and quercetin significantly mitigated the increase in these indicators. Moreover, XBJ and quercetin both downregulated the expression of key proteins in the NLRP3 inflammasome pathway in the ALI model. Similar to the ROS inhibitor N-acetylcysteine (NAC), XBJ and quercetin significantly decreased M1 polarization markers like CD86 and inducible nitric oxide synthase (iNOS), while increasing M2 polarization markers such as CD206 and arginase-1 (Arg-1). Notably, the overexpression of NLRP3 was able to reverse the inhibitory effect of XBJ on macrophage M1 polarization.

XBJ inhibits the M1 polarization of alveolar macrophages by targeting ROS-mediated NLRP3 inflammasome signaling, thereby reducing the inflammatory response. These results indicate that XBJ may offer a novel therapeutic strategy for ALI/ARDS by modulating macrophage polarization and inflammation.