Nitric oxide and prostaglandin E2 synthesis inhibitory activities of diarylheptanoids from the barks of Alnus japonica Steudel

Nine known diarylheptanoids (11 -9) isolated from the barks of Alnus japonica were evaluated for their inhibitory activities on nitric oxide (NO) and prostagrandin E-2 (COX-2) production in interferon-gamma (INF-,gamma) and lipopolysaccharide (LPS)-activated RAW 264.7 cells in vitro. The NO and COX-2 levels were moderately reduced by the addition of compounds (1-9). Among these compounds, compounds 6 and 8 inhibited NO production in a dose dependent manner with an IC50 of 16.7 and 27.2 mug/mL, respectively (positive control, L-NMMA; 22.8 mug/mL, and compounds 6, 7, 8, and 9 reduced the COX-2 level in a dose dependent manner with an IC50 of 20.7, 25.7, 25.0, and 27.3 mug/mL, respectively (positive control, indomethacin; 26.2 mug/ml). An analysis of the structural activity relationship among these diarylheptanoids suggests that the presence of a keto-enol group in the heptane moiety or a caffeoyl group in the aromatic ring were important for the efficacy on the inhibitory activities of NO and COX-2 production.