Platycodon grandiflorus decoction against lipopolysaccharide (LPS)-induced acute lung injury via Keap1/Nrf2/ARE signaling pathway

Background: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a severe inflammatory disease with high incidence and mortality rates. The traditional Chinese medicine Platycodon grandiflorus decoction (PGD) exerts protective effects against lipopolysaccharide (LPS)-induced ALI via the PI3K/AKT/NF-κB pathway, but its underlying molecular mechanisms require further elucidation. Objectives: This study aimed to investigate the molecular mechanism underlying the protective effects of PGD against LPS-induced ALI. Methods: In-vivo experiments employed an LPS-induced ALI mouse model to assess PGD's therapeutic potential. Complementary in-vitro studies examined the molecular mechanisms of PGD-enriched serum using human pulmonary epithelial (A549) and microvascular endothelial (HPMEC) cell lines. Nrf2 involvement in PGD-mediated protection was verified through siRNA-mediated gene silencing and subsequent functional validation. Results: Both in-vitro and in vivo analyses demonstrated that PGD effectively protects pulmonary tissues from LPS-induced damage. PGD administration notably enhanced Nrf2 nuclear translocation and decreased Keap1 expression at the protein and transcriptional levels, while promoting the expression of HO-1 and NQO1 biomarkers. Notably, Nrf2 gene silencing abolished PGD's therapeutic effects, including its anti-apoptotic properties. Conclusions: PGD's therapeutic efficacy in LPS-induced ALI is mediated through modulation of the Keap1/Nrf2/ARE signaling pathway.