CDDO-imidazolide ameliorates sepsis-induced ARDS by enhancing mitophagy via the Nrf2 pathway to prohibit alveolar macrophage pyroptosis and HMGB1 release

• CDDO-imidazolide, a potent Nrf2 activator, significantly reduces alveolar macrophage pyroptosis and HMGB1 release in sepsis-induced ARDS models. • The protective effect is mediated through enhancement of PINK1/Parkin-dependent mitophagy, which is dependent on Nrf2 activation. • In vivo, CDDO-imidazolide alleviates lung injury and reduces NLRP3 inflammasome and HMGB1 levels in septic mice, and these effects are reversed by the Nrf2 inhibitor ML385. • These findings highlight CDDO-imidazolide as a promising therapeutic candidate for sepsis-associated ARDS by targeting the Nrf2/mitophagy/pyroptosis axis.