Exploring the Anti‐Inflammatory Molecular Mechanism of Gentiana szechenyii Kanitz. Based on UPLC–MS/MS Combined With Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation

ABSTRACT This study explored the anti‐inflammatory mechanisms of Gentiana szechenyii Kanitz. (GS), a Tibetan medicinal herb, by combining UPLC–MS/MS, network pharmacology, molecular docking, and molecular dynamics (MD) simulation. Using the lipopolysaccharide (LPS)‐induced RAW264.7 cell inflammation model, the anti‐inflammatory effect of GS was confirmed by detecting the release amount of nitric oxide (NO) and the levels of inflammatory factors tumor necrosis factor (TNF) and interleukin‐6 (IL‐6). UPLC–MS/MS identified 40 constituents, whereas network analysis predicted 5 core compounds (isovitexin 4′,7‐diglucoside, loganin, isoorientin‐2″‐ O ‐glucoside, gentiopicroside, sweroside), 5 key targets (TNF, IL‐6, GAPDH, epidermal growth factor receptor [EGFR], HSP90AA1), and three critical pathways (PI3K‐Akt, hypoxia inducible factor‐1 [HIF‐1], IL‐17). Molecular docking showed strong binding between core compounds and targets; the binding energies were all lower than −5 kcal mol −1 , among which isovitexin 4′,7‐diglucoside had the lowest binding energy to EGFR (−9.4 kcal mol −1 ). MD simulation confirmed stable binding of TNF with the five core compounds. This study comprehensively clarifies the pharmacodynamic material basis and mechanism of action of GS in anti‐inflammation, providing an experimental basis for further development and utilization. It is expected to be applied to the adjuvant treatment of inflammation‐related diseases such as chronic bronchitis and pharyngitis in the future, thereby promoting the modernization of Tibetan medicine.