Fucoxanthin decreases lipopolysaccharide‐induced acute lung injury through the inhibition of RhoA activation and the NF‐κB pathway

• Published in: Environmental toxicology 2022-09, Vol.37 (9), p.2214-2222
• Main Authors: Lee, Chien‐Ying, Chen, Shih‐Pin, Huang‐Liu, Rosa, Gau, Shuo‐Yan, Li, Yi‐Ching, Chen, Chun‐Jung, Chen, Wen‐Ying, Wu, Chun‐Nan, Kuan, Yu‐Hsiang
• Format: Article
• Language: English
• Subjects: acute lung injury; AKT protein; Algae; Anticancer properties; Bronchus; Colour; Cytokines; Fucoxanthin; Histopathology; Homology; Infiltration; Inflammatory diseases; Injury prevention; JNK protein; Kinases; Lavage; Leukocytes (neutrophilic); Lipopolysaccharides; LPS; Lung diseases; Lungs; MAP kinase; Neutrophils; NF‐κB; Oxidative stress; Phosphorylation; Phytoplankton; Pretreatment; Protein kinase; RhoA; RhoA protein; Seaweeds; Xanthophylls
• ISSN: 1520-4081; 1522-7278
• DOI: 10.1002/tox.23587

Fucoxanthin is a natural pigment widely distributed in macroalgae and microalgae. An orange‐colored xanthophyll, it has several bioactive effects, including anticancer, anti‐obesity, oxidative stress reduction, and anti‐inflammation. Acute lung injury (ALI) caused by acute infections or injurious stimuli to the lung tissues is a severe pulmonary inflammatory disease. To date, no evidence has shown ALI to be reduced by fucoxanthin through activation of Ras homolog family member A (RhoA) and the nuclear factor (NF)‐κB pathway in lipopolysaccharide (LPS)‐treated mice. Pretreatment with fucoxanthin inhibited histopathological changes in lung tissues and neutrophil infiltration into bronchoalveolar lavage fluid induced by LPS in ALI mice. Moreover, LPS‐induced proinflammatory cytokine expression and neutrophil infiltration were inhibited by fucoxanthin in a concentration‐dependent manner. Pretreatment of mice with fucoxanthin inhibited NF‐κB phosphorylation and IκB degradation in the lungs of mice with LPS‐induced ALI. We further found that phosphorylation of Akt and p38 mitogen‐activated protein KINASE (MAPK) was inhibited by fucoxanthin. By contrast, the phosphorylation of extracellular signal‐regulated kinase and c‐Jun N‐terminal kinase was not inhibited by fucoxanthin. Furthermore, we found that the activation of RhoA was inhibited by fucoxanthin in LPS‐induced ALI. On the basis of these results, we propose that fucoxanthin disrupts the RhoA activation‐mediated phosphorylation of Akt and p38 MAPK, leading to NF‐κB activation in mice with LPS‐induced ALI.