Inhibitory effects and molecular mechanism of dieckol isolated from marine brown alga on COX-2 and iNOS in microglial cells.
To identify the neuroprotective effect of dieckol, a hexameric compound of phloroglucinol isolated from marine brown alga, Ecklonia cava , this study investigated the anti-inflammatory effect of dieckol on lipopolysaccharide (LPS)-stimulated murine BV2 microglia and elucidated the molecular mechanism. The results showed that dieckol suppresses LPS-induced production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a dose-dependent manner, without causing cytotoxicity. It also significantly reduced the generation of proinflammatory cytokines, such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α. Moreover, dieckol significantly reduced LPS-induced nuclear factor κB (NF-κB) and p38 mitogen-activated protein kinases (MAPKs) activation, as well as reactive oxygen species (ROS) production. Taken together, the inhibition of LPS-induced NO and PGE(2) production might be due to the suppression of NF-κB and p38 MAPK signal pathway and, at least in part, by inhibiting the generation of ROS. Hence, these effects of dieckol might assist therapeutic treatment for neurodegenerative diseases that are accompanied by microglial activation.
Jung
Won-Kyo
WK
Department of Marine Life Science and Marine Life Research Center, Chosun University, Gwangju 501-759, Republic of Korea.
Heo
Soo-Jin
SJ
Jeon
You-Jin
YJ
Lee
Chang-Min
CM
Park
Yeong-Min
YM
Byun
Hee-Guk
HG
Choi
Yung Hyun
YH
Park
Sae-Gwang
SG
Choi
Il-Whan
IW
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001572:Benzofurans / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000201:enzymology* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D000459:Phaeophyceae / Q000737:chemistry*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
D000893:Anti-Inflammatory Agents; D001572:Benzofurans; D052246:Cyclooxygenase 2 Inhibitors; D016207:Cytokines; D004791:Enzyme Inhibitors; D016328:NF-kappa B; C503840:dieckol; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone