Two enone fatty acids isolated from Gracilaria verrucosa suppress the production of inflammatory mediators by down-regulating NF-kappaB and STAT1 activity in lipopolysaccharide-stimulated RAW 264.7 cells

Hye-Ja Lee; Hung-The Dang; Gyeoung-Jin Kang; Eun-Jin Yang; Sun-Soon Park; Weon-Jong Yoon; Jee H Jung; Hee-Kyoung Kang; Eun-Sook Yoo

doi:10.1007/s12272-009-1320-0

Two enone fatty acids isolated from Gracilaria verrucosa suppress the production of inflammatory mediators by down-regulating NF-kappaB and STAT1 activity in lipopolysaccharide-stimulated RAW 264.7 cells

Arch Pharm Res. 2009 Mar;32(3):453-62. doi: 10.1007/s12272-009-1320-0. Epub 2009 Apr 23.

Authors

Hye-Ja Lee¹, Hung-The Dang, Gyeoung-Jin Kang, Eun-Jin Yang, Sun-Soon Park, Weon-Jong Yoon, Jee H Jung, Hee-Kyoung Kang, Eun-Sook Yoo

Affiliation

¹ Department of Pharmacology, College of Medicine, Jeju National University, Jeju, 690-756, Korea.

PMID: 19387591
DOI: 10.1007/s12272-009-1320-0

Abstract

Gracilaria verrucosa is a common marine red alga that has anti-oxidant and anti-cancer properties. Recently, we reported that anti-inflammatory constituents of G. verrucosa operate through an unknown mechanism. For this reason, we isolated two enone fatty acids from G. verrucosa and investigated their molecular mechanism in LPS-stimulated RAW264.7 cells. We found that the two compounds inhibited the production of inflammatory markers (nitric oxide, TNF-alpha, and IL-6) in a dose-dependent manner. We next studied the effects of G. verrucosa compounds on LPS-induced signaling pathways. The two compounds suppressed NF-kappaB reporter activity by interfering with nuclear translocation of NF-kappaB and suppressed JAK/STAT (p-STAT1) signaling. These results suggest that G. verrucosa inhibits the production of inflammatory mediators (NO, TNF-alpha, and IL-6) by suppressing the activation of NF-kappaB and the phosphorylation of STAT1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Inflammatory Agents / isolation & purification
Anti-Inflammatory Agents / pharmacology*
Cell Line
Dose-Response Relationship, Drug
Down-Regulation
Fatty Acids / isolation & purification
Fatty Acids / pharmacology*
Gracilaria* / chemistry
Inflammation Mediators / metabolism*
Interleukin-6 / metabolism
Janus Kinases / metabolism
Lipopolysaccharides / pharmacology*
Macrophages / drug effects*
Macrophages / immunology
Macrophages / metabolism
Mice
Nitric Oxide / metabolism
Nitric Oxide Synthase Type II / metabolism
Phosphorylation
Promoter Regions, Genetic / drug effects
STAT1 Transcription Factor / metabolism*
Signal Transduction / drug effects
Transcription Factor RelA / genetics
Transcription Factor RelA / metabolism*
Tumor Necrosis Factor-alpha / metabolism

Substances

Anti-Inflammatory Agents
Fatty Acids
Inflammation Mediators
Interleukin-6
Lipopolysaccharides
Rela protein, mouse
STAT1 Transcription Factor
Stat1 protein, mouse
Transcription Factor RelA
Tumor Necrosis Factor-alpha
lipopolysaccharide, Escherichia coli O111 B4
Nitric Oxide
Nitric Oxide Synthase Type II
Janus Kinases