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 (10(4) U/kg). Nuclear factor (NF)-kappa B activation could be potential treatment for sepsis. NF-kappa B signaling components were determined by western-blotting. IL-6, IL-1 beta, TNF-alpha production, and NF-kappa B 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-1 beta, and TNF-alpha, in a prophylactic manner in the LPS-induced sepsis mouse model. Meanwhile, FX significantly inhibits phosphorylation of the NF-kappa B signaling pathway induced by LPS at the cellular level and reduces the nuclear translocation of NF-kappa B. The IC50 for suppressing the expression of NF-kappa B was 11.08 +/- 0.78 mu M in the THP1-Lucia (TM) NF-kappa B 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 mu M in Raw267.4 macrophage cells. It is likely that the molecules with the ability of targeting NF-kappa B activation and inflammasome assembly, such as fucoxanthin, are interesting subjects to be used for treating sepsis.
[1]Fujian Normal Univ, Coll Life Sci, Biomed Res Ctr South China, Fujian Key Lab Innate Immune Biol, Fuzhou, Fujian, Peoples R China;
[2]Fujian Normal Univ, Publ Serv Platform Ind Dev Technol Marine Biol Me, Ctr Engn Technol Res Microalgae Germplasm Improve, Southern Inst Oceanog, Fuzhou, Fujian, Peoples R China;
[3]Univ Texas Southwestern Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA;
[4]Natl Taiwan Ocean Univ, Inst Marine Biol, Keelung, Taiwan;
[5]Natl Taiwan Ocean Univ, Ctr Excellence Oceans, Keelung, Taiwan;
[6]Chinese Acad Sci, Ctr Ocean Mega Sci, Inst Oceanol, Qingdao, Shandong, Peoples R China;
[7]Qingdao Natl Lab Marine Sci & Technol, Lab Marine Biol & Biotechnol, Qingdao, Shandong, Peoples R China;
[8]Fudan Univ, Huashan Hosp, Div Neurocrit Care, Shanghai, Peoples R China;
[9]Fisheries Res Inst Fujian, Fujian Collaborat Innovat Ctr Exploitat & Utiliza, Key Lab Cultivat & High value Utilizat Marine Org, Xiamen, Fujian, Peoples R China
(8.0+极速模式)