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

Jiaqi Xu,1– 3,&ast; Conghan Jiao,2– 4,&ast; Haiwei Du,2,5 Xiaojing Guo,1– 3 Mutian Wang,1– 3 Yuening Ma,1,2 Yanzhong Yin,1,2 Min Liu,1,2 Rongjiang Shao2,5 1Department of Infectious Diseases, the First Teaching Hospital of Tianjin University of TCM, Tianjin, People’s Republic of China; 2National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, People’s Republic of China; 3Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 4Department of Hematology, the First Teaching Hospital of Tianjin University of TCM, Tianjin, People’s Republic of China; 5Department of General Surgery, the First Teaching Hospital of Tianjin University of TCM, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rongjiang Shao, Department of General surgery, The First Teaching Hospital of Tianjin University of TCM, No. 88, Changling Road, Xiqing District, Tianjin, 300381, People’s Republic of China, Tel +86 13920987128, Email [email protected] Min Liu, Department of Infectious Diseases, The First Teaching Hospital of Tianjin University of TCM, No. 88, Changling Road, Xiqing District, Tianjin, 300381, People’s Republic of China, Tel +86 13132296378, Email [email protected]: 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.Keywords: Xijiao Dihuang Decoction, sepsis-induced acute lung injury, network pharmacology, mechanism of action, PI3K/Akt signaling pathway, anti-inflammatory, antioxidant, anti-apoptotic