Revealing the Anti‐Inflammatory Mechanisms of <scp> <i>Zingiber officinale</i> </scp> Roscoe Through Network Pharmacology and Experimental Validation

A comprehensive approach combining network pharmacology and in vitro validation was employed to systematically elucidate the anti-inflammatory mechanisms of Zingiber officinale Roscoe. First, its components were preliminarily identified via UPLC-Q-Exactive Orbitrap MS/MS, whose targets were obtained from the Swiss Target Prediction database and the Traditional Chinese Medicine Systems Pharmacology database. Inflammation-related targets were retrieved from GeneCards and OMIM databases. Overlapping targets between compound-related and inflammation-related genes were identified, followed by the construction of PPI networks and component-target networks. Subsequent GO and KEGG pathway enrichment analyses were performed. Through network pharmacology analysis, 6-Shogaol (20), 8-Shogaol (24), and 8-Gingerol (19) emerged as core active components, while AKT1, MAPK3, EGFR, SRC, and STAT3 were identified as key targets. KEGG enrichment analysis revealed that the anti-inflammatory effects were primarily associated with AGE-RAGE, PI3K-Akt, MAPK, TNF, and IL-17 signaling pathways. Subsequently, molecular docking was employed to validate the binding affinity between core components and key targets. Finally, anti-inflammatory activity was validated in vitro using the LPS-stimulated RAW 264.7 macrophage model, and gene expression was assessed via qRT-PCR. Collectively, this study elucidates the active constituents and molecular mechanisms underlying the anti-inflammatory action of Z. officinale, providing a theoretical basis for its development, utilization, and clinical application.