6,6'-Bieckol suppresses inflammatory responses by down-regulating nuclear factor-κB activation via Akt, JNK, and p38 MAPK in LPS-stimulated microglial cells.
OBJECTIVE
Microglial activation has been implicated in many neurological disorders for its inflammatory and neurotrophic effects. In this study, we investigated the pharmaceutical properties of 6,6'-bieckol on the regulation of nuclear factor-κB (NF-κB) activation responsible to the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 using lipopolysaccharide (LPS)-stimulated BV2 and murine primary microglial cells. Meterials and methods: The levels of nitric oxide (NO), prostaglandin E2 (PGE)2, and pro-inflammatory cytokines were measured by Griess assay and enzyme-linked immunosorbent assay. The levels of iNOS, COX-2, mitogen-activated protein kinases (MAPKs), and Akt were measured using Western blot. Nuclear translocation and transcriptional activation of NF-κB were determined by immunofluorescence and reporter gene assay, respectively.


RESULTS
We found that 6,6'-bieckol decreased the expression of iNOS and COX-2 as well as pro-inflammatory cytokines in LPS-stimulated BV2 and primary microglial cells in a dose-dependent manner. 6,6'-Bieckol inhibited activation of NF-κB by preventing the degradation of inhibitor κB (IκB)-α and led to prevent the nuclear translocation of NF-κB/p65 subunit. Moreover, 6,6'-bieckol inhibited the phosphorylation of Akt, JNK, and p38 MAPK.


CONCLUSIONS
These results indicate that the anti-inflammatory effect of 6,6'-bieckol on LPS-stimulated microglial cells is mainly regulated by the inhibition of IκB-α/NF-κB and JNK/p38 MAPK/Akt pathways, supporting biochemical characteristics of the compound for therapeutic agent against neuroinflammatory diseases caused by microglial activation.
a Department of Food Science and Nutrition , Pukyong National University , Busan , Republic of Korea ;
A-Reum
AR
Kim
b College of Pharmacy, Pusan National University , Busan , Republic of Korea ;
Bonggi
B
Lee
a Department of Food Science and Nutrition , Pukyong National University , Busan , Republic of Korea ;
Eun-Ji
EJ
Joung
a Department of Food Science and Nutrition , Pukyong National University , Busan , Republic of Korea ;
Wi-Gyeong
WG
Gwon
c Department of Pathological Science , School of Veterinary Medicine, Louisiana State University , Baton Rouge , LA , USA ;
Tadanobu
T
Utsuki
d Department of Marine Biology , Gyeongsang National University , Tongyooung , Republic of Korea.
Nam-Gil
NG
Kim
a Department of Food Science and Nutrition , Pukyong National University , Busan , Republic of Korea ;
Hyeung-Rak
HR
Kim
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects* / Q000276:immunology; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D008070:Lipopolysaccharides / Q000633:toxicity*; D048670:MAP Kinase Kinase 4 / Q000276:immunology*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D017628:Microglia / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology*; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology*
D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4
6,6′-bieckol; Ecklonia stolonifera; inflammation; microglial cells; nuclear factor-κB