Aciculatin inhibits lipopolysaccharide-mediated inducible nitric oxide synthase and cyclooxygenase-2 expression via suppressing NF-B and JNK/p38 MAPK activation pathways

Objectives. natural products have played a significant role in drug discovery and development. inflammatory mediators such as inducible nitric oxide synthase (inos) and cyclooxygenase-2 (cox-2) have been suggested to connect with various inflammatory diseases. in this study,we explored the anti-inflammatory potential of aciculatin (8-((2r,4s,5s,6r)-tetrahydro-4,5- dihydroxy-6-methyl-2h-pyran-2-yl)-5-hydroxy-2-(4-hydroxyphenyl) -7-methoxy-4h-chromen-4-one),one of main components of chrysopogon aciculatis,by examining its effects on the expression and activity of inos and cox-2 in lipopolysaccharide (lps)-activated macrophages. methods. we used nitrate and prostaglandin e2(pge2) assays to examine inhibitory effect of aciculatin on nitric oxide (no) and pge2levels in lps-activated mouse raw264.7 macrophages and further investigated the mechanisms of aciculatin suppressed lps-mediated inos/cox-2 expression by western blot,rt-pcr,reporter gene assay and confocal microscope analysis. results: aciculatin remarkably decreased the lps (1 g/ml)-induced mrna and protein expression of inos and cox-2 as well as their downstream products,no and pge2respectively,in a concentration-dependent manner (1-10 m). such inhibition was found,via immunoblot analyses,reporter gene assays,and confocal microscope observations that aciculatin not only acts through significant suppression of lps-induced nf-b activation,an effect highly correlated with its inhibitory effect on lps-induced ib kinase (ikk) activation,ib degradation,nf-b phosphorylation,nuclear translocation and binding of nf-b to the b motif of the inos and cox-2 promoters,but also suppressed phosphorylation of jnk/p38 mitogen-activated protein kinases (mapks). conclusion: our results demonstrated that aciculatin exerts potent anti-inflammatory activity through its dual inhibitory effects on inos and cox-2 by regulating nf-b and jnk/p38 mapk pathways. © 2011 hsieh et al; licensee biomed central ltd.