Fucoidan Isolated from Saccharina japonica Inhibits LPS-Induced Inflammation in Macrophages via Blocking NF-κB, MAPK and JAK-STAT Pathways

Abstract

Fucoidan has been reported to have a variety of biological activities. However, different algae species, extraction methods, harvesting seasons, and growth regions lead to the structural variation of fucoidan, which would affect the bioactivities of fucoidan. To date, the anti-inflammatory properties and the underlying mechanism of fucoidan from brown alga Saccharina japonica (S. japonica) remain limited. The aims of the present study were to investigate the structure, the anti-inflammatory properties, and the potential molecular mechanisms of fucoidan isolated from S. japonica (SF6) against lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. SF6 was characterized using high performance liquid gel permeation chromatography (HPGPC), Fourier transform infrared spectroscopy (FTIR), and nuclear magnetic resonance spectroscopy (NMR), and observed to be rich in fucose, galactose, and sulfate. Additionally, results showed that SF6 remarkably inhibited LPS-induced production of various inflammatory mediators and pro-inflammation cytokines, including nitric oxide (NO), NO synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-β (IL-β), and interleukin-6 (IL-6). A mechanism study showed that SF6 could effectively inhibit inflammatory responses through blocking LPS-induced inflammation pathways, including nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), and Janus kinase (JAK)-2 and signal transducer and activator of transcription (STAT)-1/3 pathways. These results suggested that SF6 has the potential to be developed as an anti-inflammatory agent applied in functional food.

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 ].…”

“…At 25 μg/mL of LJNF3, the expression fold of COX-2 was determined to be 12.84 ± 1.31, which was decreased to 59.10% compared to that of the LPS-only treated group. For assessing the inhibitory effect of fucoidan on iNOS and COX-2 expression, some research indicated that the protein levels of iNOS and COX-2 were suppressed with pretreatment of 50–200 μg/mL [ 49 ]. Compared with the previous research, purity fucoidan did not exert effective anti-inflammatory activity at the concentration of 50 μg/mL, but LJNF3 inhibited the production of iNOS and COX-2 at 25 μg/mL.…”

“…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]. Ye et al (2020) indicated that the purified fucoidan, from 50 to 200 μg/mL (246.4 KDa), with high sulfate group (36.94%) and rich in fucose (24.15%), had better anti-inflammatory activity [49]. Wang et al (2020) reported that fucoidan, at 50-400 μg/mL (131.5 KDa), with 9.07% sulfate and 47.15% fucose, showed evident anti-inflammatory activity, and it was composed of (1→3)-α-L-fucose residues with abundant branches consisting of α-L-fucose and β-D-galactose residues [50].…”

Present Status, Limitations and Future Directions of Treatment Strategies Using Fucoidan-Based Therapies in Bladder Cancer

“…It is a heparin-like molecule with an α-1,3-linked fucose and an α-1,4-linked fucose with branches attached at the C2 position [ 5 ]. It is known to have various biological activities, including antibacterial, anti-inflammatory, antioxidant, and immunomodulatory effects [ 6 , 7 , 8 ]. Additionally, fucoidan has been favored owing to its low toxicity in vivo, including in humans [ 9 , 10 ].…”