A Sulfated Polysaccharide from Saccharina japonica Suppresses LPS-Induced Inflammation Both in a Macrophage Cell Model via Blocking MAPK/NF-κB Signal Pathways In Vitro and a Zebrafish Model of Embryos and Larvae In Vivo

Abstract

Inflammation is a complicated host-protective response to stimuli and toxic conditions, and is considered as a double-edged sword. A sulfated Saccharinajaponica polysaccharide (LJPS) with a sulfate content of 9.07% showed significant inhibitory effects against lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophage cells and zebrafish. Its chemical and structural properties were investigated via HPLC, GC, FTIR, and NMR spectroscopy. In vitro experiments demonstrated that LJPS significantly inhibited the generation of nitric oxide (NO) and prostaglandin E2 (PGE2) via the downregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression and suppressed pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1β production via the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signal pathways in LPS-induced RAW 264.7 cells. Moreover, LJPS showed strong protective effects against LPS-induced inflammatory responses in zebrafish, increasing the survival rate, reducing the heart rate and yolk sac edema size, and inhibiting cell death and the production of intracellular reactive oxygen species (ROS) and NO. Its convenience for large-scale production and significant anti-inflammatory activity indicated the potential application of LJPS in functional foods, cosmetics, and pharmaceutical industries.

Molecular Mechanism of Anti-Inflammatory Activities of a Novel Sulfated Galactofucan from Saccharina japonica

“…According to previous reports, fucoidan in brown seaweed generally plays a good anti-inflammatory effect in 200 or 400 μg/mL [ 49 , 50 ], and the structure of fucoidan is relatively complex [ 49 , 50 , 51 ]. For example, the fucoidan fraction of S. japonica showed the optimal anti-inflammatory activity in concentrations of 50–200 μg/mL [ 49 ] and 50–400 μg/mL [ 50 ], respectively.…”

“…According to previous reports, fucoidan in brown seaweed generally plays a good anti-inflammatory effect in 200 or 400 μg/mL [ 49 , 50 ], and the structure of fucoidan is relatively complex [ 49 , 50 , 51 ]. For example, the fucoidan fraction of S. japonica showed the optimal anti-inflammatory activity in concentrations of 50–200 μg/mL [ 49 ] and 50–400 μg/mL [ 50 ], respectively. Besides, some studies reviewed the biological activities of fucoidan, and considered that the content of fucose, sulfate groups, molecular weight, and position of the glycosidic linkage would affect the biological activities of fucoidan [ 32 , 52 , 53 ].…”

“…RAW 264.7 macrophage cells (MFN048; FDCC, Shanghai, China) were cultured at 37 °C in a humidified incubator (HERAcell 150 i, Thermo, Waltham, MA, USA) with 5% CO 2 in DMEM supplemented with 1% penicillin–streptomycin and 10% fetal bovine serum [ 50 , 51 ]. The effects of LJNF3 with 3.125, 6.25, 12.5 and 25 μg/mL on the cell viability were determined by MTT assay at 490 nm [ 66 ].…”

“…RAW 264.7 cells were pretreated with various concentrations of LJNF3 for 1 h and then stimulated with or without LPS (1 μg/mL) for 24 h. The supernatants were collected for the analysis of pro-inflammatory cytokines release. The TNF-α, IL-1β, and IL-6 were determined by ELISA kits (Dakewei, Shenzhen, China) [ 50 , 51 ].…”

“…Values with p < 0.05 were significantly different. Different letters indicate a significant difference between the compared pairs of individual means, while the same letter means no significant difference between the compared pairs of individual means [ 50 , 51 ].…”