Anti-Inflammatory Activity of Diterpenoids fromCelastrus orbiculatusin Lipopolysaccharide-Stimulated RAW264.7 Cells

Celastrus orbiculatus Thunb has been known as an ethnopharmacological medicinal plant for antitumor, anti-inflammatory, and analgesic effects. Although various pharmacological studies of C . orbiculatus extract has been reported, an anti-inflammatory mechanism study of their phytochemical constituents has not been fully elucidated. In this study, compounds 1 – 17 , including undescribed podocarpane-type trinorditerpenoid ( 3 ), were purified from C . orbiculatus 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 1 – 17 , nitric oxide (NO) secretion was evaluated in LPS-treated murine macrophages, RAW264.7 cells. Among compounds 1 – 17 , deoxynimbidiol ( 1 ) and new trinorditerpenoid ( 3 ) showed the most potent inhibitory effects (IC 50 : 4.9 and 12.6 μ 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 β , IL-6, and tumor necrosis factor- (TNF-) α . Its inhibitory activity of proinflammatory mediators is contributed by suppressing the activation of nuclear transcription factor- (NF-) κ B and mitogen-activated protein kinase (MAPK) signaling cascades including p65, inhibition of NF- κ B (I κ B), extracellular signal-regulated kinase (ERK), c-Jun NH 2 -terminal kinase (JNK), and p38. Therefore, these results demonstrated that diterpenoids 1 and 3 obtained from C . orbiculatus may be considered a potential candidate for the treatment of inflammatory diseases.