Mechanistic Insights Into Dihydromyricetin‐Mediated Therapy for Acute Lung Injury: An Integrated Analysis via Network Pharmacology, Molecular Docking, Dynamics Simulations, and Experimental Validation

ABSTRACT Dihydromyricetin (DHM) has attracted widespread attention due to its unique biological activity and potential clinical applications. However, the current understanding of DHM's mechanism of action in the treatment of acute lung injury (ALI) is unclear. This study aims to elucidate the efficacy and potential mechanisms of DHM in treating ALI. Based on network pharmacology, 64 candidate therapeutic targets of DHM for the treatment of ALI were identified. Subsequently, a protein–protein interaction network was constructed through the STRING database, and 8 core targets were subsequently identified. Molecular docking and dynamics simulations showed that DHM forms stable binding with core targets (MMP9, KDR, HIF1A, and PPARG). In vivo experimental results showed that DHM significantly improved lung pathological damage in CLP‐induced ALI mice, as demonstrated by a significant improvement in survival rate, a decrease in protein content, and inflammation levels in bronchial alveolar lavage fluid, and a decrease in the wet/dry weight ratio of lung tissue. In addition, DHM significantly downregulates the expression levels of HIF1A, KDR, and MMP9, while also upregulating the expression levels of PPARG. The findings establish a theoretical framework for the mechanistic understanding of DHM in ALI treatment and support its potential for future translational and clinical investigations.