Isocyperol, isolated from the rhizomes of Cyperus rotundus, inhibits LPS-induced inflammatory responses via suppression of the NF-κB and STAT3 pathways and ROS stress in LPS-stimulated RAW 264.7 cells

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 E-2 (PGE(2)) 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-ibeta (IL-1 beta), 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-kappa B) 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, PGE(2), 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-kappa B 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. (C) 2016 Elsevier B.V. All rights reserved.