3,4-Seco-Dammarane Triterpenoid Saponins with Anti-inflammatory Activity Isolated from the Leaves of Cyclocarya paliurus.

Cyclocarya paliurus is commonly used for the prevention and treatment of hypertension, diabetes, and inflammation in South China. Although research on the anti-inflammatory effects of C. paliurus leaves has been reported, no active anti-inflammatory compounds have been identified. In the present study, RAW 264.7 cells were used to establish a bioactivity-guided identification model to verify the inhibitory effects of C. paliurus leaves on inflammation and identify the anti-inflammatory constituents. The anti-inflammatory bioactivity-guided isolation of an extract from the leaves of C. paliurus led to the isolation and characterization of eighteen dammarane triterpenoid saponins, including eleven new 3,4-seco-dammarane triterpenoid saponins (1-11), the structures of which were identified by nuclear magnetic resonance (NMR), mass spectrometry (MS) and comparison with literature data. Compounds 7, 8, 10, and 11 strongly inhibited the release of nitric oxide (NO), with IC50 values ranging from 8.23 μM to 11.23 μM. These four compounds significantly decreased the secretion of prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Furthermore, compound 7 markedly decreased the expression of the proteins inducible nitric-oxide synthase (iNOS), nuclear factor kappa-B (NF-κB/p65) and cyclooxygenase-2 (COX-2). In addition, the structure-activity relationships of the isolates were investigated. The results suggest that 3,4-seco-dammarane triterpenoid saponins may be used as potential anti-inflammatory drugs and warrant further investigation.