Objective:

To systematically elucidate the protective effects and underlying mechanisms of Baihe Gujin Decoction (BHGJD) against sepsis-induced acute lung injury (ALI).

Approach:

• Chemical Characterization: Characterized the chemical constituents of BHGJD using mass spectrometry.
• Network Pharmacology: Predicted potential protective mechanisms through network pharmacology.
• In Vivo Model: Established a cecal ligation and puncture (CLP) mouse model to evaluate BHGJD’s protective effects.
• Histopathological Assessment: Conducted histopathological assessment and serum inflammatory cytokine analysis.
• Multi-Omics Analysis: Performed lung tissue RNA sequencing and untargeted metabolomics to explore molecular mechanisms.
• Protein Validation: Validated key proteins using Western blot, immunohistochemistry, and immunofluorescence.
• In Vitro Studies: Used (+)-catechin to treat lipopolysaccharide-induced MLE-12 cells and measured various cellular parameters.

Key Findings:

• BHGJD significantly ameliorated CLP-induced ALI, as evidenced by improved histological architecture and reduced inflammatory cytokine levels.
• Activated Nrf2/GPX4-associated antioxidant response, reducing lipid peroxidation and restoring mitochondrial homeostasis.
• Induced PPARα/CPT1A-associated metabolic remodeling towards fatty acid utilization.
• Reduced inflammatory lipid mediators and altered mTOR signaling were observed.

Interpretation:

BHGJD alleviates sepsis-induced ALI through enhancement of antioxidant defense, metabolic reprogramming, and suppression of inflammatory mediators.

Limitations:

• The study primarily utilized animal models, which may not fully replicate human responses.
• Further clinical studies are needed to validate the findings in human subjects.

Conclusion:

BHGJD provides an integrated mechanistic framework for its protective actions against sepsis-induced ALI.