Luteolin Glycoside From <i>Dracocephalum moldavica</i> L. Attenuates COPD by Modulating TLR4 Expression and Alveolar Cross‐Talk

ABSTRACT Chronic obstructive pulmonary disease (COPD) is associated with inflammation of the airway and lung parenchyma with limited airflow due to continued exposure to harmful particulate matter or gases. Currently, primary bronchodilators and anti‐inflammatory drugs face issues such as rapid drug resistance and significant side effects. During the COVID‐19 pandemic, luteolin glycoside, a traditional Chinese medicine compound, demonstrated promising clinical efficacy in treating pneumonia and related conditions. Using CS, we established mouse and cellular models of COPD to validate the therapeutic efficacy of LGU against COPD and assess changes in mouse lung function. We employed Transwell chambers to coculture NR8383 and RLE‐6TN cells, simulating the inflammatory microenvironment of the lung. By screening public databases, we identified potential binding sites where LGU may exert its effects. Seahorse technology was utilized to evaluate energy metabolism in model cells. Compared to COPD model mice and cells, COPD progression was significantly alleviated following LGU treatment; LGU can inhibit the expression level of TLR4 and reduce inflammatory cytokine levels in NR8383 cells while activating CSF2R expression, thereby alleviating inflammatory infiltration and oxidative damage. Following improvement of the inflammatory microenvironment, NF‐κB–p65 activity decreases in RLE‐6TN cells, subsequently activating PPARγ and enhancing energy production efficiency. This promotes the formation of complete alveoli, increasing alveolar oxygen content and improving lung function. LGU can improve lung function and alleviate COPD by reducing inflammatory infiltration and oxidative damage and enhancing energy production efficiency in alveolar cells. It may be considered for development as an effective therapeutic agent for COPD.