Xijiao Dihuang Decoction for Sepsis-Induced Acute Lung Injury: Network Pharmacology and Molecular Dynamics Insights.

OBJECTIVE: This study investigates the therapeutic mechanisms of Xijiao Dihuang Decoction (XJDHD) in sepsis-induced acute lung injury (SALI) through an integrated approach, including network pharmacology, molecular docking, molecular dynamics simulations, and in vitro experiments. METHODS: Network pharmacology identified active ingredients and targets in Xijiao Dihuang Decoction. Molecular docking and dynamics simulations evaluated binding affinity and stability with key targets. In vitro experiments on LPS-stimulated A549 cells substantiated Xijiao Dihuang Decoction's anti-inflammatory, antioxidant, and anti-apoptotic effects. RESULTS: Network pharmacology identified 20 active components among 182 Sepsis-Induced Acute Lung Injury targets. Molecular docking revealed strong binding affinity (binding energies ≤ -5.0 kcal/mol) for β-sitosterol with AKT1 and TNF. Molecular dynamics confirmed the complex stability. In vitro experiments demonstrated that Xijiao Dihuang Decoction significantly reduced inflammatory cytokines IL-6, TNF-α, and IL-1β (p<0.001), increased SOD and CAT mRNA (p<0.05), downregulated MyD88 mRNA (p<0.05), and modulated apoptosis-related proteins (Bax, Bcl-2, Cleaved-Caspase-3; p<0.05). The modulation of the PI3K/Akt pathway was confirmed by p-PI3K and p-Akt expression (p<0.05). CONCLUSION: Xijiao Dihuang Decoction exhibits therapeutic efficacy in treating Sepsis-Induced Acute Lung Injury through its anti-inflammatory, antioxidant, and anti-apoptotic effects, and by modulating the PI3K/Akt pathway. This study provides experimental evidence for Xijiao Dihuang Decoction's mechanisms, highlighting its potential. However, additional in vivo and clinical investigations are required to validate its efficacy.