Stilbene Dimers, Phenylpropanoids, and Aurones from the Rhizomes of Heterosmilax japonica and Their Anti-inflammatory Activities

Four previously undescribed phenolic compounds, 1–4, including a racemic stilbene dimer featuring a rare benzobicyclo[4.2.1]nonene motif (1a/1b), a racemic 1,2-diarylpropanoid (3a/3b), and an aurone (4), along with 14 known metabolites, were isolated from the rhizomes of Heterosmilax japonica. The structures of compounds 1–4 were identified by extensive HRESIMS, NMR data analysis, X-ray diffraction crystallography, and ECD calculation. The anti-inflammatory activities of compounds 1–16 were evaluated by the lipopolysaccharide (LPS)-stimulated RAW264.7 cell model. Compounds 3 and 7 significantly inhibited the release of NO in LPS-stimulated RAW264.7 cells, with IC50 values of 5.7 and 5.3 μM, respectively. Moreover, the expression of pro-inflammatory cytokines (TNFα, IL-6, IL-1β, and NOS2) was also blocked by them in a dose-dependent manner. Mechanistically, compounds 3 and 7 suppressed the TLR4/NF-κB signaling pathway in RAW264.7 cells.