Danhong injection alleviates sepsis-induced acute lung injury by regulating AGE/RAGE/AKT pathway

Danhong injection (DHI), a standardized Chinese medicine derived from Salvia miltiorrhizaBunge and Carthamus tinctoriusL., is widely used for cardiovascular diseases due to its anti-inflammatory and antioxidant properties. However, its mechanism in sepsis-induced acute lung injury (SALI) remains unclear.

To evaluate the therapeutic effect of DHI on SALI and elucidate its underlying mechanisms.

Chemical components of DHI were identified by UPLC-Q-TOF/MS. A SALI mouse model was established by cecal ligation and puncture (CLP), and lung injury was assessed via histopathology, wet/dry weight ratio, myeloperoxidase (MPO) activity, and inflammatory cytokines. In vitro, LPS-stimulated RAW264.7 macrophages were used to measure cytokine levels. Network pharmacology and molecular docking were employed to predict targets and pathways, followed by experimental validation.

Fifty-two bioactive compounds were identified in DHI. In CLP mice, DHI (5 and 10 mL/kg) significantly alleviated lung pathological damage, reduced pulmonary oedema (wet/dry ratio), decreased MPO activity, and lowered TNF-α and IL-6 levels. In vitro, DHI suppressed LPS-induced TNF-α, IL-6, and IL-1β expression. Network analysis highlighted the AGE-RAGE pathway as central, with IL-6, TNF, and AKT1 core targets and kaempferol, caffeic acid showing strong binding affinity in molecular docking. DHI also downregulated RAGE, NF-κB, and AKT protein expression in lung tissue.

DHI attenuates SALI likely through multi-component, multi-target regulation of the AGE/RAGE/AKT pathway, highlighting its potential as a novel therapeutic agent for sepsis-related lung injury.