Ethanol extract of Sauropus spatulifolius and its active constituents attenuate LPS-induced acute lung injury via NF-κB inhibition and Nrf2 activation

Sauropus spatulifolius (S. spatulifolius), a key medicinal herb in the Lingnan region, is traditionally used to treat respiratory and digestive ailments. This study explored its anti-inflammatory constituents and mechanisms against LPS-induced acute lung injury (ALI). The ethanol crude extract (CE) of S. spatulifolius showed significant nitric oxide (NO) inhibition activity (IC₅₀: 81.93 ± 1.913 μg/mL). Through bioactivity-guided fractionation, active subfractions (Fr. C, Fr. C4, Fr. C4c, Fr. C4d) and two bioactive compounds (1 and 2) were identified, all exhibiting potent dose-dependent NO suppression. The extract and its constituents downregulated iNOS and COX-2 expression, suppressed NF-κB signaling, reduced the level of intracellular reactive oxygen species (ROS), and activated the Nrf2 pathway. In vivo, they alleviated LPS-induced ALI, highlighting their anti-inflammatory and antioxidant potential. S. spatulifolius may serve as a natural therapeutic or dietary supplement for ALI by targeting NF-κB and Nrf2 pathways.