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

Four previously undescribed phenolic compounds, <b>1</b>-<b>4</b>, including a racemic stilbene dimer featuring a rare benzobicyclo[4.2.1]nonene motif (<b>1a</b>/<b>1b</b>), a racemic 1,2-diarylpropanoid (<b>3a</b>/<b>3b</b>), and an aurone (<b>4</b>), along with 14 known metabolites, were isolated from the rhizomes of <i>Heterosmilax japonica</i>. The structures of compounds <b>1</b>-<b>4</b> were identified by extensive HRESIMS, NMR data analysis, X-ray diffraction crystallography, and ECD calculation. The anti-inflammatory activities of compounds <b>1</b>-<b>16</b> were evaluated by the lipopolysaccharide (LPS)-stimulated RAW264.7 cell model. Compounds <b>3</b> and <b>7</b> 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 <b>3</b> and <b>7</b> suppressed the TLR4/NF-κB signaling pathway in RAW264.7 cells.