Anti-inflammatory effects of sargachromenol-rich ethanolic extract of Myagropsis myagroides on lipopolysaccharide-stimulated BV-2 cells.

Sunghee Kim,Eun-Ji Joung,Min-Sup Lee,Wi-Gyeong Gwon,Bonggi Lee,Hyeung-Rak Kim,Na-Young Yoon

doi:10.1186/1472-6882-14-231

Abstract

BackgroundExcessive pro-inflammatory cytokine production from activated microglia contributes to neurodegenerative diseases, thus, microglial inactivation may delay the progress of neurodegeneration by attenuating the neuroinflammation. Among 5 selected brown algae, we found the highest antioxidant and anti-neuroinflammatory activities from Myagropsis myagroides ethanolic extract (MME) in lipopolysaccharide (LPS)-stimulated BV-2 cells.MethodsThe levels of nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines were measured by Griess assay and enzyme linked immunesorbent assay. The levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), mitogen-activated protein kinases (MAPKs), and Akt were measured using Western blot. Nuclear translocation and transcriptional activation of nuclear factor-κB (NF-κB) were determined by immunefluorescence and reporter gene assay, respectively.ResultsMME inhibited the expression of iNOS and COX-2 at mRNA and protein levels, resulting in reduction of NO and PGE2 production. As a result, pro-inflammatory cytokines were reduced by MME. MME also inhibited the activation and translocation of NF-κB by preventing inhibitor κB-α (IκB-α) degradation. Moreover, MME inhibited the phosphorylation of extracellular signal regulated kinases (ERKs) and c-Jun N-terminal kinases (JNKs). Main anti-inflammatory compound in MME was identified as sargachromenol by NMR spectroscopy.ConclusionsThese results indicate that the anti-inflammatory effect of sargachromenol-rich MME on LPS-stimulated microglia is mainly regulated by the inhibition of IκB-α/NF-κB and ERK/JNK pathways.

Highlights

Excessive pro-inflammatory cytokine production from activated microglia contributes to neurodegenerative diseases, microglial inactivation may delay the progress of neurodegeneration by attenuating the neuroinflammation
M. myagroides showed highest antioxidant activity expressed as ROS scavenging activity (EC50, 112.4 ± 8.2 μg/mL) and anti-inflammatory activity expressed as the inhibition of nitric oxide (NO) production (EC50, 6.84 ± 0.78 μg/mL) in LPS-treated BV-2 cells
Myagropsis myagroides ethanolic extract (MME) inhibits NO and prostaglandin E2 (PGE2) production in LPS-stimulated BV-2 cells To evaluate the effect of MME on LPS-induced production of inflammatory mediators including NO and PGE2, BV-2 cells were pretreated with 0–25 μg/mL MME for 2 h and stimulated with LPS for 24 h

Summary

Introduction

Excessive pro-inflammatory cytokine production from activated microglia contributes to neurodegenerative diseases, microglial inactivation may delay the progress of neurodegeneration by attenuating the neuroinflammation. Activated microglia produce various neurotoxic factors including inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2), and pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6. Pathogenic roles of inflammatory mediators and cytokines have been implicated in various inflammatory and neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, trauma, multiple sclerosis, and cerebral ischemia [5,6].the modulation of microglial activation is important for the prevention or relief of neuroinflammation. Exposure to LPS stimulates phosphorylation, ubiquitination, and degradation of IκB-α, resulting in nuclear translocation of NF-κB by dissociation of NF-κB-IκB-α complex for the transcription of target genes [11]. The MAPKs such as extracellular signal-regulated kinase (ERK), p38 MAPK, and c-Jun NH2-terminal kinase (JNK) have been involved in the transcriptional regulations of inflammatory genes [12,13]

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