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Int Immunopharmacol ; 38: 61-9, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27240136

ABSTRACT

The rhizomes of Cyperus rotundus (cyperaceae) have been used in Korean traditional medicines for treating diverse inflammatory diseases. However, little is known about the biological activities of isocyperol, a sesquiterpene isolated from C. rotundus, and their associated molecular mechanisms. In this study, we found that isocyperol significantly inhibited lipopolysaccharide (LPS)-induced production of nitrite oxide (NO) and prostaglandin E2 (PGE2) and suppressed LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the mRNA and protein levels in RAW 264.7 macrophages. In addition, isocyperol downregulated the LPS-induced expression of several proinflammatory cytokines, such as interleukin-1beta (IL-1ß), IL-6, and monocyte chemotactic protein-1 (MCP-1). Isocyperol treatment suppressed the LPS-induced nuclear translocation and transcriptional activation of nuclear factor-kappaB (NF-κB) in macrophages. Moreover, the activation of STAT3, another proinflammatory signal, was suppressed by isocyperol in LPS-stimulated RAW 264.7 cells. Isocyperol pretreatment also induced heme oxygenase-1 (HO-1) expression and reduced LPS-stimulated reactive oxygen species (ROS) accumulation in macrophages. Furthermore, isocyperol significantly increased the survival rate and attenuated serum levels of NO, PGE2, and IL-6 in LPS-induced septic shock mouse model. Taken together, these data indicate that isocyperol suppress septic shock through negative regulation of pro-inflammatory factors through inhibition of the NF-κB and STAT3 pathways and ROS. To our knowledge, this is the first report on the biological activity of isocyperol and its molecular mechanism of action.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Cyperus/immunology , Macrophages/drug effects , NF-kappa B/metabolism , STAT3 Transcription Factor/metabolism , Sepsis/drug therapy , Sesquiterpenes/pharmacology , Animals , Dinoprostone/metabolism , Interleukin-6/metabolism , Lipopolysaccharides/immunology , Macrophages/immunology , Male , Mice , Mice, Inbred C57BL , Nitric Oxide Synthase Type II/metabolism , Oxidative Stress/drug effects , RAW 264.7 Cells , Reactive Oxygen Species/metabolism , Rhizome , Signal Transduction/drug effects
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