Anti-Inflammatory Diterpenoids from the Aerial Parts of <i>Isodon suzhouensis</i>

A phytochemical investigation of the aerial parts of <i>Isodon suzhouensis</i> resulted in the isolation of nine <i>ent</i>-kauranoid diterpenes, six of which were previously undescribed. The structures of these compounds were elucidated comprehensively using a combination of 1<i>D</i>/2D NMR spectroscopy and high-resolution electrospray ionization mass spectrometry (HRESIMS). Among the isolated compounds, compounds <b>2</b> and <b>3</b> exhibited intramolecular <i>SN</i> ₂ tautomerism, a phenomenon further explained through the Fukui function and free energy calculations of the transition states of the reactions via the DFT calculation. Compound <b>7</b> is particularly noteworthy as it represents a novel case of C-3/C-4 carbon bond breakage in an <i>ent</i>-kauranoid diterpene, highlighting a unique structural modification in this class of natural products. All of the isolates were evaluated for their inhibitory effects on LPS-induced RAW 264.7 macrophages. Compound <b>8</b> emerged as a promising candidate, demonstrating significant inhibitory effects. Further studies confirmed that compound <b>8</b> suppresses the gene expression of the pro-inflammatory cytokines. The underlying anti-inflammatory mechanism of compound <b>8</b> was therefore investigated and shown to be related to the inhibition of the NF-κB signaling pathway activation.