Evaluation of the Immunomodulatory Effects of Fucoidan Derived from Cladosiphon Okamuranus Tokida in Mice

Tomori, Makoto; Nagamine, Takahiko; Miyamoto, Tomofumi; Iha, Masahiko

doi:10.3390/md17100547

Cited by 39 publications

(21 citation statements)

References 28 publications

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“…Compared to drugs,they are non-toxic food-grade ingredients which rarely cause side effects [ 3 ]. An array of studies has reported its antioxidant [ 4 ],immunoregulatory [ 5 ],antiviral [ 6 ] and anti-inflammatory [ 7 ] activities. More recently, fucoidan has been shown to alleviate metabolic syndrome [ 8 ], benefit angiogenesis [ 9 ] and bone health [ 10 ].Besides,a number of studies have confirmed that fucoidan exerts antitumor effects.…”

Section: Introductionmentioning

confidence: 99%

Antitumor effect and molecular mechanism of fucoidan in NSCLC

Chen

Sun

Wei

et al. 2021

BMC Complement Med Ther

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Background Fucoidan, a water-soluble polysaccharide, exerts anticoagulant and antiviral functions. It was recently reported that fucoidan also exerts an antitumor function. Lung cancer is one of the most common cancers in the world. The aim of this study was to investigate anti-tumor,apoptosis and anti-metastasis effects of fucoidan in both cell-based assays and mouse xenograft model, as well as to clarify possible role of m-TOR pathway in the protection. Methods In vitro: Different concentrations of fucoidan were given to act on non-small cell lung cancer (NSCLC) cell lines A549 and H1650. The effects of fucoidan on cell proliferation were observed by detecting cyclin expression levels, CCK8 and EDU experiments and cloning experiments. The apoptotic level was detected by flow cytometry and the apoptotic protein level was detected by Westernblot. By detecting the expression of adhesion molecules, the expression of matrix metalloproteinase (MMP) family, and Transwell cell invasion and migration experiment, the effect of fucoidan on cell adhesion, invasion and migration was observed. Meanwhile the effect of fucoidan on angiogenesis was observed by detecting the expression of vascular endothelial growth factor (VEGF). In vivo experiment: An animal model of NSCLC cell mouse subcutaneous xenograft tumor was established to analyze the correlation between the consumption of fucoidan and the size and volume of xenograft tumor through gross observation. Through immunohistochemical staining and immunofluorescence double staining, ki67 and cell adhesion molecules (E-cadherin, N-cadherin and CD31) and VEGF-A in the tumor were detected, and the correlation between the amount of fucoidan and the above indexes was analyzed. Results Fucoidan inhibited the proliferation and angiogenesis of NSCLC cells via the mTOR pathway and promoted their apoptosis by increasing the Bax/Bcl-2 ratio. Not only that, fucoidan inhibited NSCLC cell invasion via epithelial–mesenchymal transformation (EMT). The mice fed fucoidan exhibited significant reductions in tumor volumes and weights. These indicators (Ki67, VEGF-A,N-cadherin) were decreased and E-cadherin expression was up-regulated in A549 mice that treated with fucoidan. The results showed that fucoidan inhibited tumor proliferation in vivo by affecting the expression of related proteins. Conclusion Fucoidan conveys antitumor effects and our results represent an ideal therapeutic agent for NSCLC.

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Section: Introductionmentioning

confidence: 99%

Antitumor effect and molecular mechanism of fucoidan in NSCLC

Chen

Sun

Wei

et al. 2021

BMC Complement Med Ther

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“…The bioactive properties of fucoidan preparations have been assessed in a range of in vitro and animal models [5] and include demonstrated antimicrobial [6], antiviral [7] and anticancer [8] effects. While evidence from animal models suggests fucoidans may also possess immune-modulating effects [9,10], the ability of fucoidans to act as potential modulators of mucosal health generally, and mucosal immune function appears underappreciated and requires further investigation given (i) the fucose-based structure of fucoidans, (ii) the role of fucose as a terminal sugar in human mucin glycoproteins [11], and (iii) evidence from ex vivo tissue preparations suggesting fucose may regulate gut motility [12].…”

Section: Introductionmentioning

confidence: 99%

Fucoidan Supplementation Restores Fecal Lysozyme Concentrations in High-Performance Athletes: A Pilot Study

et al. 2020

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Nutritional strategies to help promote immune competence are of particular interest for a range of population groups. This study aimed to assess the potential impacts of fucoidan, a seaweed-derived bioactive polysaccharide, on gut markers of immunity and inflammation. A group of professional team-sport athletes were selected for inclusion in the study given the recognized potential for intense physical activity to induce alterations in immune function. A retrospective analysis was performed on stored fecal samples which had been collected from professional team-sport athletes (n = 22) and healthy adults (n = 11) before and after seven days of supplementation with fucoidan (Fucus vesiculosus/Undaria pinnatifida extract, 1 g/d). Fecal concentrations of calprotectin, secretory immunoglobulin A (sIgA) and lysozyme were determined using enzyme-linked immunosorbent assays. The supplement was well tolerated by participants with no adverse events reported. At baseline, fecal lysozyme concentrations were ~73% higher in the healthy adults compared to the professional athletes (p = 0.001). For the professional athletes, a significant (~45%) increase in fecal lysozyme was observed following the supplementation period (p = 0.001). These data suggest that fucoidan supplementation may have the potential to promote the secretion of antimicrobial peptides in specific population groups and contribute to the regulation of mucosal immune health.

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“…Numerous studies have shown that CD4 + T cells are the predominant contributors to inflammatory responses and the regulators of hepatic granuloma and fibrosis in schistosomiasis [18,21]. Moreover, fucoidan has been reported to activate the growth of T and B cells in the spleen [39,40], and we further speculated that fucoidan could alleviate hepatic immunopathology by affecting the subsets of CD4 + T cells. Remarkably, Treg cells are widely recognized to respond to local milieu to behave as subtypes that are equipped with distinct immunosuppressive programs to function in inflammatory settings.…”

Section: Discussionmentioning

confidence: 75%

Therapeutic potential of fucoidan in the reduction of hepatic pathology in murine schistosomiasis japonica

Bai

Wang

et al. 2020

Parasites Vectors

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Background Hepatic granuloma formation and fibrosis as the consequence of tissue entrapped eggs produced by female schistosomes characterize the pathology of Schistosoma japonicum infection. It has been proposed that fucoidan, a sulfated polysaccharide existing naturally in brown seaweed Fucus vesiculosus, plays a diversified role to perform immunomodulatory activities. However, whether fucoidan functions in the host hepatic pathology is unknown and identifying the potential mechanism that is responsible for hepatic improvement is still necessary. Methods We evaluated the hepatic pathology from S. japonicum-infected mice after treatment with fucoidan. qRT-PCR and immunofluorescence were used to detect the pro- or anti-inflammatory factors and the phosphorylated p65 in the livers. In addition, flow cytometry was also performed to investigate the T cell subsets in the S. japonicum-infected mice after treatment with fucoidan, and functional molecules relatively specific to Treg cells were detected in vitro. Furthermore, macrophages were treated with fucoidan in vitro and to detect the inflammatory cytokines. Results Treatment with fucoidan significantly reduced the hepatic granuloma size and fibrosis response during S. japonicum infection. The attenuated phospho-p65 protein levels and the mRNA levels of pro-inflammatory cytokines (IL-6, IL-12 and TNF-α) were observed in the livers from fucoidan-treated S. japonicum-infected mice; however, the mRNA levels of anti-inflammatory cytokines (IL-4 and IL-13) were increased. In addition, the infiltration of Treg cells was significantly enhanced both in the livers and spleens from fucoidan-treated S. japonicum-infected mice. Consistent with this, the mRNA levels of IL-10 and TGF-β were dramatically increased in the livers from S. japonicum-infected mice after fucoidan treatment. Furthermore, in vitro stimulated splenocytes with fucoidan resulted in increasing Treg cells in splenocytes as well as the functional expression of CC chemokine receptor type 4 (CCR4) and CXC chemokine receptor type 5 (CXCR5) in Treg cells. Additionally, fucoidan promoted the mRNA levels of IL-4 and IL-13 in macrophages. Conclusions These findings suggest an important role of natural fucoidan in reducing hepatic pathology in the progress of S. japonicum infection with a stronger Treg response, which may reveal a new potential therapeutic strategy for hepatic disease caused by parasitic chronic infection.

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Evaluation of the Immunomodulatory Effects of Fucoidan Derived from Cladosiphon Okamuranus Tokida in Mice

Cited by 39 publications

References 28 publications

Antitumor effect and molecular mechanism of fucoidan in NSCLC

Antitumor effect and molecular mechanism of fucoidan in NSCLC

Fucoidan Supplementation Restores Fecal Lysozyme Concentrations in High-Performance Athletes: A Pilot Study

Therapeutic potential of fucoidan in the reduction of hepatic pathology in murine schistosomiasis japonica

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