Anti-Inflammatory Activity of Diterpenoids from in Lipopolysaccharide-Stimulated RAW264.7 Cells.

Thunb has been known as an ethnopharmacological medicinal plant for antitumor, anti-inflammatory, and analgesic effects. Although various pharmacological studies of . extract has been reported, an anti-inflammatory mechanism study of their phytochemical constituents has not been fully elucidated. In this study, compounds -, including undescribed podocarpane-type trinorditerpenoid (), were purified from . and their chemical structure were determined by high-resolution electrospray ionization mass (HRESIMS) and nuclear magnetic resonance (NMR) spectroscopic data. To investigate the anti-inflammatory activity of compounds -, nitric oxide (NO) secretion was evaluated in LPS-treated murine macrophages, RAW264.7 cells. Among compounds -, deoxynimbidiol () and new trinorditerpenoid () showed the most potent inhibitory effects (IC: 4.9 and 12.6 M, respectively) on lipopolysaccharide- (LPS-) stimulated NO releases as well as proinflammatory mediators, such as inducible nitric oxide (iNOS), cyclooxygenase- (COX-) 2, interleukin- (IL-) 1, IL-6, and tumor necrosis factor- (TNF-) . Its inhibitory activity of proinflammatory mediators is contributed by suppressing the activation of nuclear transcription factor- (NF-) B and mitogen-activated protein kinase (MAPK) signaling cascades including p65, inhibition of NF-B (IB), extracellular signal-regulated kinase (ERK), c-Jun NH-terminal kinase (JNK), and p38. Therefore, these results demonstrated that diterpenoids and obtained from . may be considered a potential candidate for the treatment of inflammatory diseases.