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Phlorofucofuroeckol A Suppresses Expression of Inducible Nitric Oxide Synthase, Cyclooxygenase-2, and Pro-inflammatory Cytokines via Inhibition of Nuclear Factor-κB, c-Jun NH2-Terminal Kinases, and Akt in Microglial Cells

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Abstract

Microglial activation has been implicated in many neurological disorders for its inflammatory and neurotrophic effects. In this study, we investigated the effects of phlorofucofuroeckol A isolated from Ecklonia stolonifera Okamura on the production of inflammatory mediators in lipopolysaccharide (LPS)-stimulated microglia. Pre-treatment of phlorofucofuroeckol A attenuated the productions of nitric oxide, prostaglandin E2, and pro-inflammatory cytokines in LPS-stimulated microglia. Profoundly, phlorofucofuroeckol A treatment showed inactivation of nuclear factor-κB (NF-κB) by preventing the degradation of inhibitor κB-α and the nuclear translocation of p65 NF-κB subunit. Moreover, phlorofucofuroeckol A inhibited the activation of c-Jun NH2-terminal kinases (JNKs), p38 mitogen-activated protein kinase (MAPK), and Akt, but not that of extracellular signal-regulated kinase. These results indicate that phlorofucofuroeckol A inhibits the LPS-induced expression of inflammatory mediators through inactivation of NF-κB, JNKs, p38 MAPK, and Akt pathways. These findings suggest that phlorofucofuroeckol A can be considered as a nutraceutical candidate for the treatment of neuroinflammation in neurodegenerative diseases.

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Abbreviations

BSA:

Bovine serum albumin

COX-2:

Cyclooxygenase 2

DAPI:

4′,6-Diamidino-2-phenylindole

DCF-DA:

2′,7′-Dichlorofluorescein diacetate

DMEM:

Dulbecco’s modified Eagle’s medium

DMSO:

Dimethyl sulfoxide

ERK:

Extracellular signal-regulated kinase

ELISA:

Enzyme-linked immunosorbent assay

FBS:

Fetal bovine serum

GC–MS:

Gas chromatography–mass spectrometry

HPLC:

High-performance liquid chromatography

IκB:

Inhibitor κB

IL:

Interleukin

iNOS:

Inducible nitric oxide synthase

JNK:

c-Jun NH2-terminal kinase

LPS:

Lipopolysaccharide

MAPK:

Mitogen-activated protein kinase

NF-κB:

Nuclear factor-κB

NO:

Nitric oxide

PBS:

Phosphate-buffered saline

PGE2 :

Prostaglandin E2

PI3K:

Phosphoinositide 3-kinase

PMSF:

Phenylmethylsulfonyl fluoride

RT–PCR:

Reverse transcription–polymerase chain reaction

TBST:

Tris-buffered saline with Tween-20

TNF-α:

Tumor necrosis factor-α

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ACKNOWLEDGMENTS

This work was financially supported by the Fishery Commercialization Technology Development Program (iPET109200-3) of Ministry for Food, Agriculture, Forestry and Fisheries, and Brain Busan 21 Program, Republic of Korea.

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Authors and Affiliations

  1. Molecular Nutrition Laboratory, Department of Food Science and Nutrition, Pukyong National University, 599-1 Daeyeon-3-dong, Nam-gu, Busan, 608-737, South Korea

    A-Reum Kim, Min-Sup Lee, Ji-Woong Choi, Jae-Il Kim & Hyeung-Rak Kim

  2. Department of Pathobiological Science, School of Veterinary Medicine, Skip Bertman Drive, Baton Rouge, LA, 70803, USA

    Tadanobu Utsuki

  3. Department of Medical Genetic Engineering, Keimyung University School of Medicine, Daegu, 700-712, South Korea

    Byeong-Churl Jang

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  1. A-Reum Kim
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Kim, AR., Lee, MS., Choi, JW. et al. Phlorofucofuroeckol A Suppresses Expression of Inducible Nitric Oxide Synthase, Cyclooxygenase-2, and Pro-inflammatory Cytokines via Inhibition of Nuclear Factor-κB, c-Jun NH2-Terminal Kinases, and Akt in Microglial Cells. Inflammation 36, 259–271 (2013). https://doi.org/10.1007/s10753-012-9542-6

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