Abstract

Background: Fucoxanthin (FX), a xanthophyll pigment which occurs in marine brown algae with remarkable biological properties, has been proven to be safe for consumption by animals. Although FX has various pharmacological effects including anti-inflammatory, anti-tumor, anti-obesity, antioxidant, anti-diabetic, anti-malarial, and anti-lipid, in vivo protective effect against sepsis has not been reported. In this study, we aimed at evaluation the efficacy of the FX in a model of sepsis mouse. Methods: FX was successfully isolated from Conticribra weissflogii ND-8 for the first time. The FX was identified by thin-layer chromatography (TLC), high-performance liquid chromatography-mass spectrometry (HPLC-MS), and nuclear magnetic resonance (NMR). Animals were randomly divided into 9 groups, including Sham group (mouse received an intraperitoneal injection of normal saline 1.0 ml/kg), FX-treated (0.1–1.0 ml/kg), Lipopolysaccharide (LPS)-treated (20 mg/kg), FX+LPS-treated (0.1–10.0 mg/kg and 20 mg/kg, respectively), and urinastatin groups (104 U/kg). Nuclear factor (NF)-κB activation could be potential treatment for sepsis. NF-κB signaling components were determined by western-blotting. IL-6, IL-1β, TNF-α production, and NF-κB activation were evaluated by ELISA and immunofluorescent staining in vitro. Results: FX was found to decrease the expression of inflammatory cytokines including IL-6, IL-1β, and TNF-α, in a prophylactic manner in the LPS-induced sepsis mouse model. Meanwhile, FX significantly inhibits phosphorylation of the NF-κB signaling pathway induced by LPS at the cellular level and reduces the nuclear translocation of NF-κB. The IC50 for suppressing the expression of NF-κB was 11.08 ± 0.78 μM in the THP1-Lucia™ NF-κB cells. Furthermore, FX also inhibits the expression of inflammatory factors in a dose-dependent manner with the IC50 inhibition of IL-6 production was 2.19 ± 0.70 μM in Raw267.4 macrophage cells. It is likely that the molecules with the ability of targeting NF-κB activation and inflammasome assembly, such as fucoxanthin, are interesting subjects to be used for treating sepsis.

Highlights

  • Fucoxanthin (FX) is an important carotenoid present in algae, such as edible brown algae and diatoms, and was first isolated from brown seaweeds

  • The molecular data in the present paper suggested that C. weissflogii (ND8) and other Conticribra species form a monophyletic group separated from some species of Thalassiosira, which was described as a new species from three additional areas of Korea (Park and Lee, 2014)

  • As nuclear factor (NF)-κB plays a central role in the regulation of inflammatory responses and macrophage functions, we evaluated its role in FX-mediated protective effects in RAW264.7 cells and in liver homogenates of LPS-treated mice

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Summary

Introduction

Fucoxanthin (FX) is an important carotenoid present in algae, such as edible brown algae and diatoms, and was first isolated from brown seaweeds. FX has a unique structure and exhibits potential advantages with a variety of pharmacological activities, including anti-inflammatory, anti-tumor, anti-obesity, antioxidant, anti-diabetic, anti-malarial, and anti-lipid effects (Maeda, 2015). The raw materials used for FX extraction are often derived from brown algae, including kelp, sargassum, and wakame, which grow seasonally. FX is only present in the surface cortical cells of the brown algae at a low concentration and its production efficiency is very low. FX has various pharmacological effects including anti-inflammatory, anti-tumor, anti-obesity, antioxidant, anti-diabetic, anti-malarial, and anti-lipid, in vivo protective effect against sepsis has not been reported. We aimed at evaluation the efficacy of the FX in a model of sepsis mouse

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