Protective effect of glycyrrhizin, a direct HMGB1 inhibitor, on particulate matter-induced lung injury via suppression of NF-κB signaling and endoplasmic reticulum stress.

Particulate matter (PM) is a pervasive environmental pollutant that poses significant risks to public health, particularly by inducing oxidative stress, inflammation, and apoptosis, resulting in severe respiratory system damage. The release of high-mobility group box 1 (HMGB1), a critical pro-inflammatory mediator, plays a pivotal role in the pathogenesis of PM-induced lung injury. Glycyrrhizin (GL), a direct HMGB1 inhibitor, has demonstrated robust anti-inflammatory and anti-apoptotic properties in various pathological contexts. However, its specific mechanisms in mitigating PM-induced lung injury remain undefined. This study aimed to elucidate the protective effects of GL in PM-induced lung injury using both in vivo and in vitro models. We found that PM exposure triggered HMGB1 release and promoted the secretion of pro-inflammatory mediators, leading to endoplasmic reticulum (ER) stress and activation of the NF-κB signaling pathway. GL treatment effectively inhibited HMGB1 secretion, attenuated ER stress, and suppressed NF-κB signaling pathway, thereby ameliorating PM-induced lung injury. These findings provide compelling evidence for the therapeutic potential of GL in managing PM-induced respiratory disorders and highlight its role in targeting HMGB1-mediated inflammatory pathways.