Salvianolic Acid B Inhibits Ferroptosis in Acute Lung Injury: Network Analysis and Experimental Validation

This current study aimed to decipher the anti-inflammatory, anti-ferroptosis and pronounced lung-protective activities of Salvianolic acid B (Sal B) by integrating network pharmacology and experimental confirmation across multiple aspects. The optimal target protein and the relevant molecular mechanisms for Sal B in the context of ALI were analysed using network pharmacology. Molecular dynamics simulations and BLI were performed on the core protein ALB-compound Sal B identified through molecular docking. The pharmacological efficacy of Sal B and its underlying mechanisms were further substantiated through both in vitro and in vivo experiments, utilizing the LY294002 inhibitor and si-ALB to confirm the involvement of ALB as a target. Additionally, RNA sequencing of murine lung tissues was conducted to further elucidate the molecular mechanism of Sal B. The results of network pharmacology indicated that a total of 155 potential target genes through which Sal B may exert its protective effects against ALI were identified, with essential pathways including PI3K-AKT, TNF and IL-17 signalling pathways. Molecular docking, MD, and BLI demonstrated stable binding between Sal B and the core target ALB. In vitro and in vivo evidence confirmed that Sal B attenuates LPS-induced ALI by inhibiting ferroptosis via the PI3K/AKT axis, as corroborated by LY294002 and si-ALB intervention. RNA sequencing and network pharmacological analysis synergistically revealed the PI3K/AKT pathway as a potential signalling pathway for Sal B. Sal B ameliorates sepsis-induced ALI via a defined mechanism that involves the activation of the PI3K-AKT pathway, thereby inhibiting ferroptosis both in vivo and in vitro.