Shi-Wei-Long-Dan-Hua capsule alleviates LPS-induced acute lung injury by suppressing pulmonary inflammation and the PI3K-Akt-NF-κB/MAPK axis

SWLDH was firstly confirmed to treat bacterial infection-induced ALI. • PI3K-AKT/NF- κ B and MAPK signaling pathways were confirmed as the core mechanism for SWLDH to treat ALI. • Five potential anti-ALI compounds in SWLDH were identified. Shi-Wei-Long-Dan-Hua capsule (SWLDH) is clinically used to alleviate bacterial or viral infection induced bronchitis. Recent studies have reported its effects on viral infection induced acute lung injury, broadening our understanding of its clinical applications. However, its effects against bacterial infection-induced ALI were still unclear, along with not fully elucidated chemical profile, significantly limiting its clinical application and product improvement. In this work, we aimed to systematically characterize the chemical components in SWLDH and explore its effects and mechanisms against bacterial infection-induced ALI. Results showed that SWLDH (2 g/kg/day) significantly reduced lung index, alleviated pathological injury and depressed cytokine expression in LPS-challenged mice. SWLDH also inhibited LPS-induced over-expression of iNOS and pro-inflammatory cytokines (TNF- α , IL-1 β , IL-6) in RAW264.7 cells. Moreover, 128 chemical components in SWLDH and its 32 prototypes in rats were identified by using UPLC-Q/TOF MS. Network pharmacology and Western blot were used to confirm that SWLDH can alleviate LPS- induced ALI by suppressing pulmonary inflammation and the PI3K-Akt-NF- κ B/MAPK axis. Further, five potential anti-ALI substances in SWLDH were found. This is the first time to comprehensively profile the chemical components in SWLDH and reveal its effects and mechanisms against bacterial infection-induced ALI, providing the potential substances and pharmacological data for further quality improvement and product development. Download: Download high-res image (166KB) Download: Download full-size image