Table 2.

Immunomodulatory potential of fucoidan purified from marine algae.

Study	Cell Line	Concentration	Algal Species and Fucoidan Purified	Cell Signaling Activity	Reference
Fucoidan altered the immunomodulatory markers and DCs phenotype	Human monocyte-derived dendritic cells (DCs)	100 μg/mL fucoidan	Standard fucoidan-Fucoidan purified from Fucus vesiculosus was purchased	Fucoidan elevated the expression of HLA-DR and co-stimulatory molecules of DCs, induces their Th1-promoting tumor necrosis factor α (TNF-α) and interleukin-12 (IL-12) secretion. This fucoidan is suggested to be used in DC-based vaccines for cancer immunotherapy.	Yang et al. (2008) [72]
Fucoidan express immunostimulating and DC maturing potential	Bone marrow-derived dendritic cells (DCs)	50 μg/mL	Standard fucoidan-Fucoidan purified from Fucus vesiculosus was purchased	The production of IL-12, TNF-α, major histocompatibility complex class I, II, CD54, and CD86 were promoted by fucoidan. Further fucoidan treated DCs expressed p65 (NF-κB) nuclear translocation.	Kim et al. (2008) [73]
Effect of fucoidan on spleen DCs and in vivo	Spleen dendritic cells (DCs)	C57BL/6 mice were treated with 10 mg/kg fucoidan for 24 h	Standard fucoidan-Fucoidan purified from Fucus vesiculosus was purchased	Systemic administration of fucoidan induced up-regulation of CD40, CD80 and CD86 expression and production of IL-6, IL-12 and TNF-a in spleen cDCs. Fucoidan also promoted the generation of IFN-c-producing Th1 and Tc1 cells in an IL-12-dependent manner. Moreover, fucoidan enhanced OVA-induced up-regulation of MHC class I and II on spleen cDCs and strongly prompted the proliferation of OVA-specific CD4 and CD8 T cells. The study reveals the potential of fucoidan to function as an adjuvant to induce Th1 immune response. Further, fucoidan promote CTL activation. Suggested to be useful in tumor vaccine development.	Jin et al. (2014) [74]
Immunomodulating potential of fucoidans on murine macrophages and splenocytes	RAW 264.7 cells, peritoneal macrophages and normal splenocytes	50–300 μg/mL	Anion exchange column purified fucoidan from Undaria pinnatifida	Fucoidan induced TNF-α expression from both types of macrophages. The TNF-α-inducing activity of UP-F was higher than that of FV-F. The chemokine expression (RANTES and MIP-1α) was also promoted in RAW 264.7 macrophages. The IL-6 including chemokines were significantly improved in UPF treated splenocytes.	Yoo et al. (2007) [75]
Macrophages and glial cells were examined for immune related properties against IFN-γ stimulation and fucoidan treatment	Glia (C6, BV-2) and macrophages (RAW 264.7, peritoneal primary cells)	50 μg/mL	Standard fucoidan-Fucoidan purified from Fucus vesiculosus was purchased	In glial cells IFN-γ induced inflammation was suppressed by fucoidan via JAK/STAT/IRF-1 and p-p38. The signaling positively regulated IFN-g-induced iNOS, which were inhibited by fucoidan. Contrastingly, in RAW macrophages, fucoidan promoted immune responses induced via IFN-γ. Confirmed the dual regulation of p38 in BV-2 microglia and primary peritoneal macrophages.	Do et al. (2010) [76]
In vivo viral replication and host immune defense system were assessed against fucoidan treatment	Macrophages were collected from BALB/c mice	10 μg/mL	Fucoidan prepared from Undaria pinnatifida	Fucoidan oral administration protected mice from infection with HSV-1. CTL activity of HSV-1 mice was enhanced by fucoidan. Phagocytic activity of macrophages and B cell blastogenesis in vitro was significantly stimulated by the fucoidan, while no significant change in the release of NO2− by macrophages was observed.	Hayashi et al. (2008) [3]
Immune boosting properties of fucoidan from Nizamuddinia zanardinii	RAW 264.7 macrophage cell	10, 25 and 50 μg/mL	Anion exchange column purified fucoidan.	The active fraction (F3) promoted the secretion of NO, TNF-α, IL-1β, IL-6 in RAW 264.7 macrophages. Further NK cells were activated to release TNF-α, IFN-γ, granzyme-B, perforin, NKG2D and FasL. The activity was mediated through NF-κB and MAPK pathways.	Tabarsa et al. (2020) [100]