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

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. 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. 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). 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.