Phenylbutene and Phenylpropanoid Constituents From Zingiber montanum and Their Anti-Inflammatory Activity in Macrophages.

Seventeen compounds, including seven undescribed compounds named Zingiberenes A-G (1-7), were isolated from the traditional medicinal plant Zingiber montanum. Their planar structures and absolute configurations were established by comprehensive spectroscopic analysis and ECD calculations. Evaluation of anti-inflammatory activity in LPS/IFN-γ-stimulated RAW264.7 macrophages showed that compounds 1 and 4 significantly inhibited NO production (p < 0.01), with 4 exhibiting the strongest effect. At 10 µM, both compounds also suppressed the secretion of pro-inflammatory cytokines TNF-α and IL-6 by 30%-50% (p < 0.01). Network pharmacology analysis predicted multi-target anti-inflammatory mechanisms involving IL-6, GAPDH, and PTGS2. Molecular docking further supported these findings, demonstrating that compound 4 forms a stable complex with IL-6, which aligns with the experimental NO and cytokine data. This study offers valuable insights for future research on the anti-inflammatory mechanisms of phenylbutene derivatives.