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Aim We previously demonstrated that the extract of Inula japonica Thunb (I.japonica) has antiinflammatory and antiasthmatic effects in vivo and in vitro.In an attempt to find antiinflammatory compounds from i.japonica, we recently isolated sesquiterpene lactones including 1oxo4aHeudesma5 (6), 11 (13)dien12,8βolide (OE), and 6oisovaleryloxy1hydroxy4αH1,10secoeudesma5 (10), 11 (13)dien12,8 βolide (IHS)from the extract of I.japonica, and investigated their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)stimulated RAW264.7 cells.Methods The inhibitory effects of OE and IHS on NO production in LPSinduced 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 signalproteins including inhibitory factorκB (IκB)α/Nuclear factor κB (NFκB) and mitogenactivated 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 concentrationdependent manner.To elucidate the molecular mechanism underlying the inhibition of iNOS expression, we assessed the effect of OE and IHS on LPSstimulated NFκB nuclear translocation,IκBα phosphorylation and degradation.Treatment with OE and IHS decreased the translocation of p65, via suppressing IκBα phosphorylation and degradation.Furthermore, OE and IHS inhibited LPSstimulated phosphorylation of MAPKs including extracellular signalregulated kinase 1/2 (ERKI/2), cJun Nterminal kinase (JNK) and p38.Conclusion These findings suggest that OE and IHS have inhibitory effects on production of NO via inhibition of NFκB and MAPKs activities, and might be used as potential antiinflammatory agents for the prevention and treatment of inflammatory diseases.