Abstract：Aim We previously demonstrated that the extract of Inula japonica Thunb （I. japonica） has anti-in- flammatory and anti-asthmatic effects in vivo and in vitro. In an attempt to find anti-inflammatory compounds from I. japonica, we recently isolated sesquiterpene lactones including 1-oxo-4aH-eudesma-5 （6）, 11 （ 13 ） -dien-12,8β- olide （ OE ）, and 6α-isovaleryloxy-l-hydroxy-4αH-1,10-secoeudesma-5 （ 10 ）, 11 （ 13 ）-dien-12,8β-olide （ IHS ） from the extract of I. japonica, and investigated their inhibitory effects on nitric oxide （NO） production in lipopo- lysaccharide （LPS）-stimulated RAW264.7 cells. Methods The inhibitory effects of OE and IHS on NO produc- tion in LPS-induced RAW264.7 cells were examined using Griess reagent, and the effects of OE and IHS on the expressions of nitric oxide synthase （iNOS） and its upstream signal proteins including inhibitory factor-KB （IKB）- or/Nuclear factor KB （NF-KB） and mitogen-activated protein kinases （MAPKs） were investigated by Western blot. Results Both OE and IHS reduced NO production, and blocked the protein expression of inducible nitric oxide synthase （iNOS） in a concentration-dependent manner. To elucidate the molecular mechanism underlying the inhi- bition of iNOS expression, we assessed the effect of OE and IHS on LPS-stimulated NF-KB nuclear translocation, IKB-α phosphorylation and degradation. Treatment with OE and IHS decreased the translocation of p65, via sup- pressing IKB-α phosphorylation and degradation. Furthermore, OE and IHS inhibited LPS-stimulated phosphoryla- tion of MAPKs including extracellular signal-regulated kinase 1/2 （ERK1/2） , c-Jun N-terminal kinase （JNK） and p38. Conclusion These findings suggest that OE and IHS have inhibitory effects on production of NO via inhibi- tion of NF-KB and MAPKs activities, and might be used as potential anti-inflammatory agents for the prevention and treatment of inflammatory diseases.
