Jinbei Decoction Attenuates LPS-Induced Acute Lung Injury via Suppression of TRAF6-Dependent Inflammatory Response in Macrophage.

Acute lung injury (ALI) is a life-threatening inflammatory disease of the respiratory system, characterised by high mortality rates and lack of effective clinical interventions. Emerging evidence suggests that traditional Chinese medicine (TCM) formulations may offer therapeutic benefits in managing inflammatory respiratory diseases. Jinbei decoction (JBD), a 12-herb TCM preparation currently used for pulmonary fibrosis, has shown preliminary therapeutic potential in ALI; however, mechanistic studies remain limited. This study systematically evaluated JBD's therapeutic efficacy and elucidated its molecular mechanisms in LPS-induced ALI. Survival analysis demonstrated that JBD significantly improved survival rates in a concentration-dependent manner, while histopathological evaluation revealed a marked reduction in pulmonary tissue damage. These effects were further supported by significant decreases in circulating levels of major pro-inflammatory cytokines, such as TNF-α, IL-6 and IL-1β. Network pharmacology analysis identified 111 molecular targets associated with ALI pathogenesis influenced by JBD components, highlighting the regulatory effect on inflammatory signalling pathways in macrophages as the key intervening mechanism. Specifically, JBD suppressed LPS-induced inflammatory responses by inhibiting ERK phosphorylation and blocking IKKα/β activation, thereby preventing NF-κB-dependent cytokine production in macrophages. Notably, astrapterocarpan was identified as the primary bioactive constituent of JBD through integrated network pharmacology and biochemical analyses. It was found to directly destabilise TRAF6 protein and to exhibit therapeutic efficacy comparable to that of dexamethasone in promoting histological recovery. In vivo experiments further confirmed that JBD significantly reduced TRAF6 expression in murine models, reinforcing the conclusion that its therapeutic effects are predominantly mediated by astrapterocarpan. Collectively, these findings suggest that JBD functions as an agent capable of regulating macrophage polarisation and mitigating cytokine storm through TRAF6-dependent signalling pathways, thereby providing a mechanistic basis for its potential clinical application in inflammatory lung diseases.