Molecular mechanism of a new Laminaria japonica polysaccharide on the suppression of macrophage foam cell formation via regulating cellular lipid metabolism and suppressing cellular inflammation

• Published in: Molecular nutrition & food research 2015-10, Vol.59 (10), p.2008-2021
• Main Authors: Zha, Xue‐Qiang, Xue, Lei, Zhang, Hai‐Lin, Asghar, Muhammad‐Naeem, Pan, Li‐Hua, Liu, Jian, Luo, Jian‐Ping
• Format: Article
• Language: English
• Subjects: ABC transporters; acyl coenzyme A; Animals; atherosclerosis; Carbohydrate Sequence; Cell Line - drug effects; Cell Proliferation - drug effects; chemical structure; cholesterol; Cytokines - genetics; Cytokines - metabolism; Foam cell; foam cells; Foam Cells - drug effects; Foam Cells - metabolism; gene expression; inflammation; Inflammation - drug therapy; Inflammation - metabolism; Laminaria - chemistry; Laminaria japonica; lipid metabolism; Lipid Metabolism - drug effects; Lipoproteins, LDL - metabolism; low density lipoprotein; mammals; messenger RNA; Mice; Mitogen-Activated Protein Kinase Kinases - drug effects; Mitogen-Activated Protein Kinase Kinases - metabolism; Molecular mechanism; Molecular Sequence Data; NF-kappa B - metabolism; Polysaccharide; polysaccharides; Polysaccharides - chemistry; Polysaccharides - pharmacology; protein kinases; Saccharina japonica; Structure; Toll-Like Receptor 2 - genetics; Toll-Like Receptor 4 - genetics; Toll-like receptors; vegetables
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201500113

SCOPE: Laminaria japonica is an important marine vegetable with great health benefits for preventing atherosclerosis. Since the foam cell formation is an important hallmark for the initiation of atherosclerosis, we examined the effect and underlying mechanism of a purified L. japonica polysaccharide (LJP61A) on the suppression of macrophage foam cell formation in this study. The chemical structure was further characterized. METHODS AND RESULTS: Using oxidized low‐density lipoprotein (ox‐LDL)‐induced foam cell model, we found that the cellular lipid accumulation was significantly attenuated by 25 μg/mL LJP61A. Meanwhile, LJP61A caused a remarkable decrease in mRNA expression of peroxisome proliferator‐activated receptor γ that was accompanied by the reduction of CD36 and Acyl coenzyme A: cholesterol acyltransferase‐1 mRNA levels, and the enhancement of ATP‐binding cassette transporters A1 and scavenger receptor B1 mRNA levels. Besides these, the ox‐LDL‐induced cellular inflammation was also restricted by LJP61A treatment via mammalian target of rapamycin‐mediated Toll‐like receptor 2/4‐Mitogen‐activated protein kinases/nuclear factor kappa‐B pathways. The structure of LJP61A was characterized as a repeating unit consisting of →3,6)‐α‐d‐Manp‐(1→, →4)‐α‐d‐Manp‐(1→, →4)‐2‐O‐acetyl‐β‐d‐Glcp‐(1→, →4)‐β‐d‐Glcp‐(1→, →6)‐4‐O‐SO₃‐β‐d‐Galp‐(1→, →6)‐β‐d‐Galp‐(1→, →3)‐β‐d‐Galp‐(1→, and a terminal residue of α‐d‐Glcp‐(1→. CONCLUSION: Our findings suggest that LJP61A inhibits the conversion of macrophage into foam cell via regulating cellular lipid metabolism and suppressing cellular inflammation.