6 '-O-Caffeoyldihydrosyringin isolated from Aster glehni suppresses lipopolysaccharide-induced iNOS, COX-2, TNF-alpha, IL-1 beta and IL-6 expression via NF-kappa B and AP-1 inactivation in RAW 264.7

Abstract

Previously, we found that ethyl acetate extract fraction of Aster glehni exhibited anti-hyperuricemic effects in animal models and also five new caffeoylglucoside derivatives were isolated from this fraction. In this work, we evaluated the anti-inflammatory effects of these caffeoylglucoside derivatives and found that 6'-O-caffeoyldihydrosyringin (2, CDS) most potently inhibited the LPS-induced production of nitric oxide (NO) and prostaglandin E-2 (PGE(2)) in RAW 264.7 macrophages. In addition, CDS was found to concentration-dependently reduce the production of NO, PGE(2), and the pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta) induced by LPS in macrophages. Consistent with these observations, CDS concentration-dependently inhibited LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxidase-2 (COX-2) expression at the protein level and also iNOS, COX-2, TNF-alpha, and IL-6, IL-1 beta expression at the mRNA level. Furthermore, CDS suppressed the LPS-induced transcriptional activities of nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1) as well as the phosphorylation of p65 and c-Fos. Taken together, these results suggest that the anti-inflammatory effect of CDS is associated with the downregulation of iNOS, COX-2, TNF-alpha, IL-1 beta, and IL-6 expression via the negative regulation of NF-kappa B and AP-1 activation in LPS-induced RAW 264.7 macrophages. (C) 2016 Elsevier Ltd. All rights reserved.