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: Yun Ho Choi, Guang Yu Jin, Guang Zhao Li, Guang Hai Yan
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 34 Issue 7 Pg. 959-66 ( 2011) ISSN: 1347-5215 [Electronic] Japan
• PMID: 21719998 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• DNA Primers
• Glucosides
• Lipopolysaccharides
• NF-kappa B
• Pyrans
• RNA, Messenger
• cornuside
• Nitric Oxide
• Nitric Oxide Synthase Type II
• Cyclooxygenase 2
• Protein Kinases
• Dinoprostone

Topics

• Animals
• Base Sequence
• Cell Line
• Cyclooxygenase 2 (genetics, metabolism)
• Cytokines (antagonists & inhibitors, biosynthesis)
• DNA Primers
• Dinoprostone (antagonists & inhibitors, biosynthesis)
• Glucosides (pharmacology)
• Lipopolysaccharides (antagonists & inhibitors, pharmacology)
• Macrophages (drug effects, enzymology, metabolism)
• Mice
• NF-kappa B (antagonists & inhibitors, metabolism)
• Nitric Oxide (antagonists & inhibitors, biosynthesis)
• Nitric Oxide Synthase Type II (genetics, metabolism)
• Phosphorylation
• Polymerase Chain Reaction
• Protein Kinases (metabolism)
• Pyrans (pharmacology)
• RNA, Messenger (genetics)