Identification of Q-Markers in Jie Geng Tang and exploration of mechanisms against acute lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Jie Geng Tang (JGT), composed of Platycodon grandiflorus (Jacq.) A.DC. and Glycyrrhiza uralensis Fisch. ex DC., is a classical traditional Chinese formula used for respiratory ailments cough and lung inflammation. It is traditionally believed to regulate lung Qi and clear phlegm-heat, but its active components and mechanisms remain unclear.

AIM OF THE STUDY: To identify potential Q-Markers of JGT and elucidate their synergistic mechanisms against acute lung injury using a multi-dimensional integrative strategy.

METHOD AND METHODS: Candidate components of JGT were predicted using network pharmacology and text mining, and their binding modes and stability with core targets were evaluated using molecular docking and molecular dynamics (MD) simulations. HPLC was used to validate the measurability and compatibility of the Q-Markers. The therapeutic mechanisms of JGT and its Q-Markers were investigated using in vivo and in vitro inflammatory models.

RESULT: Five potential Q-Markers were identified: Platycodin D, Glycyrrhizic acid, Glycyrrhetinic acid, Liquiritin, and Licochalcone A. HPLC analysis confirmed their consistent detectability in JGT preparations. JGT and Q-Markers exert protective effects against acute lung injury by concurrently modulating oxidative stress, mitochondrial dysfunction, and apoptosis pathways, as well as by suppressing the TLR4/NF-κB/NLRP3 inflammasome-mediated pyroptosis cascade.

CONCLUSION: This study establishes an integrated "prediction-validation-mechanism" framework for Q-Marker identification. The five identified Q-Markers not only meet the criteria of measurability and compatibility but also functionally inherit the therapeutic effects of JGT, providing a scientific basis for its quality control and the modernization of traditional Chinese medicine.