Anti‐Inflammatory Activity of Diterpenoids from Celastrus orbiculatus in 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.