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.

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.