title: Cornuside suppresses lipopolysaccharide-induced inflammatory mediators by inhibiting nuclear factor-kappa B activation in RAW 264.7 macrophages.
abstract: Cornuside, a secoiridoid glucoside compound, was isolated from the fruit of Cornus officinalis SIEB. et ZUCC. Cornuside has been reported to possess immunomodulatory and anti-inflammatory activities. However, the effects and mechanism of action of cornuside in inflammation have not been fully characterized. The present study was therefore designed to examine whether cornuside suppresses inflammatory response in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Cornuside significantly inhibited the LPS-induced production of nitric oxide, prostaglandin E(2), tumor necrosis factor-alpha, interleukin-6 (IL-6), and IL-1beta. The mRNA and protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were also decreased by cornuside. Furthermore, cornuside significantly attenuated the LPS-stimulated phosphorylation and degradation of inhibitory kappa B-alpha and the subsequent translocation of the p65 subunit of nuclear factor-kappa B (NF-κB) to the nucleus. Cornuside also reduced the phosphorylations of extracellular-signal-related kinase (ERK1/2), p38, and c-Jun N-terminal kinase (JNK1/2). These results suggest that the anti-inflammatory property of cornuside is related to the downregulations of iNOS and COX-2 due to NF-κB inhibition as well as the negative regulation of ERK1/2, p38, and JNK1/2 phosphorylations in RAW 264.7 cells.
authors: Department of Anatomy, Medical School, Institute for Medical Sciences, Chonbuk National University, Jeonju, Jeonbuk 561–756, Republic of Korea.
authors: Yun Ho
authors: YH
authors: Choi
authors: Guang Yu
authors: GY
authors: Jin
authors: Guang Zhao
authors: GZ
authors: Li
authors: Guang Hai
authors: GH
authors: Yan
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D017931:DNA Primers; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005960:Glucosides / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011494:Protein Kinases / Q000378:metabolism; D011714:Pyrans / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D016207:Cytokines; D017931:DNA Primers; D005960:Glucosides; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011714:Pyrans; D012333:RNA, Messenger; C080726:cornuside; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D011494:Protein Kinases; D015232:Dinoprostone