Abstract

Sargassum muticum (S. muticum) is a brown edible alga and widely distributed in Korea. This report was designed to evaluate the anti-inflammatory properties of apo-9′-fucoxanthinone (APO-9′) isolated from S. muticum on pro-inflammatory cytokine production. S. muticum extract (SME) exhibited significant inhibitory effects on pro-inflammatory cytokine production in bone marrow-derived macrophages (BMDMs) and dendritic cells (BMDCs). APO-9′ pre-treatment in the CpG DNA-stimulated BMDMs and BMDCs showed a strong dose-dependent inhibitory effect on interleukin (IL)-12 p40, IL-6 and tumor necrosis factor (TNF)-α production with IC50 values ranging from 5.31 to 13.79. It exhibited a strong inhibitory effect on the phosphorylation of ERK1/2 and on activator protein (AP)-1 reporter activity. APO-9′ pre-treatment exhibited significant inhibition of CpG DNA-induced production of inducible nitric oxide synthase. Taken together, these data suggest that SME and APO-9′ have a significant anti-inflammatory property and warrant further studies concerning the potentials of SME and APO-9′ for medicinal use.

Highlights

  • Toll-like receptors (TLRs) play a critical role in innate host immune response against pathogens through recognition of molecular patterns exclusively present in microorganisms [1]

  • CpG DNA induced a significant increase of IL-12 p40, IL-6 and tumor necrosis factor (TNF)-α production in bone marrow-derived macrophages (BMDMs) and bone marrow-derived dendritic cells (BMDCs)

  • These findings suggest that inhibition of CpG DNA-stimulated pro-inflammatory cytokines production by APO-9′ may correlate with blockage of the activator protein-1 (AP-1)-dependent pathway

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Summary

Introduction

Toll-like receptors (TLRs) play a critical role in innate host immune response against pathogens through recognition of molecular patterns exclusively present in microorganisms [1]. Bone marrow-derived macrophages (BMDMs) and dendritic cells (BMDCs) are vital cellular components of the innate immune system and play an important role in combating different pathogens [3]. Detection of pathogen-associated molecular patterns (PAMPs) by TLRs triggers activation of downstream signaling cascades, including nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) and the mitogen-activated protein kinase (MAPK) pathway, leading to production of pro-inflammatory cytokines [5]. The effect of APO-9′ on innate immune response has been barely studied in terms of its influence on primary murine BMDMs and BMDCs. in this study, we report the isolation and evaluation of the anti-inflammatory effects of APO-9′ from S. muticum

Results
Discussion
Experimental Section
Cell Cultures and Measurement of Cytokine Production
Cell Viability Assay
Western Blot Analysis
Luciferase Assay
Data Analysis
Conclusions
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