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

الملخص EN

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 (IC50: 4.9 and 12.6 μM, respectively) on lipopolysaccharide- (LPS-) stimulated NO releases as well as proinflammatory mediators, such as inducible nitric oxide (iNOS), cyclooxygenase- (COX-) 2, interleukin- (IL-) 1β, 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-) κB and mitogen-activated protein kinase (MAPK) signaling cascades including p65, inhibition of NF-κB (IκB), extracellular signal-regulated kinase (ERK), c-Jun NH2-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.