Fucoidan, a marine-derived sulfated polysaccharide, could potentially serve as a fascinating reservoir of anti-inflammatory substances. By exploring the potential of these marine sources, it is believed that they could effectively combat inflammatory diseases while also offering a natural and less harmful alternative to the synthetic drugs currently in use.

Hence, in this blog, I would like to share the study, “Fucoidan from Fucus vesiculosus Inhibits Inflammatory Response, Both In Vitro and In Vivo” by Lingzhi Wang et al.

The molecular weight of Fucoidan from Fucus vesiculosus (FE) is approximately 70 kDa, and it has a sulfate content of around 10%. When mouse bone marrow-derived macrophages (BMDM) were exposed to FE, the expression of CD206 and IL-10 was found to be controlled.

The assessment of the monosaccharide composition confirmed that fucose accounted for approximately 90% of the total sugar content. Smaller amounts of uronic acids (3.8%), galactose (3.3%), and xylose (2.4%) were also detected.

First, the RAW 264.7 murine macrophage cell line is often used as an initial screening model for the biological activity of natural products and to predict their potential effects. Figure 1 shows the evaluation of the effect of different FE concentrations on the viability of RAW 264.7 macrophages after 48 hours of incubation. No significant correlation was found between cell viability and FE concentration, and there were no significant variations observed across all tested conditions. For all subsequent experiments, a concentration of 0.1 mg/mL was used, and the cytotoxic effects were insignificant since macrophage survival was above 70% based on ISO 10993-5.

In this study, mouse bone marrow-derived macrophages (BMDMs) were utilized as an in vitro model. BMDMs are primary cells obtained directly from living animals. Following a 48-hour incubation with FE, the researchers quantified the levels of different cytokines, such as pro-inflammatory TNF-α and IL-12, as well as anti-inflammatory CD206 and IL-10. TNF-α activates various cell signaling pathways. IL-12 is produced early in infection and is composed of heavy and light chains. This cytokine is associated with innate and adaptive immunity through the induction of IFN-γ. IL-10 is produced through a wide variety of activated immune cells, and its primary actions are anti-inflammatory, suppressive, or autoregulatory. The main expression of the mannose receptor, CD206, is observed on macrophages and dendritic cells. This receptor, located on the cell membrane, acts as a pattern recognition receptor. It has significant involvement in both innate and adaptive immune responses.

The researchers continued their study to investigate how FE affects the expression of the mentioned cytokines in BMDMs. According to the findings presented in Figure 2, it was observed that the presence of 100 μg/mL of FE induced a slight increase in TNF-α expression when compared to the control conditions. There were no statistically significant differences. However, the expression of IL-12, CD206, and IL-10 was significantly higher than in control conditions. It was observed that the expression of CD206 and IL-10 was considerably elevated compared to the other two cytokines analyzed, suggesting that FE possesses a strong ability to combat inflammation.

The aim was to investigate how FE affects the expression of anti- and pro-inflammatory molecules (iNOs, CD206, and IL-10) in a simulated inflammatory setting. To achieve this, BMDMs were treated with LPS+ for 12 hours and then stimulated with IFN-γ. iNOS is one of the direct consequences of the inflammatory process and is a major mediator of inflammation in various cell types, as expected, iNOS expression decreased after LPS + IFN-γ stimulation, as observed in Figure 3A. The addition of FE caused a reversal of this situation, resulting in expression levels that were similar to the basal conditions. The addition of FE increased CD206 expression in response to LPS + IFN-γ stimulation. The IL-10 protein, which is also an anti-inflammatory cytokine, showed comparable patterns.

In vivo assessment of the anti-inflammatory properties of FE was conducted by injecting LPS intraperitoneally in a mouse model. Following LPS stimulation, mice injected with FE exhibited typical features of normal heart and lung tissue, along with mild morphological changes.

These findings align with the notion that fucoidan administration decreased myocardial damage. In order to verify how FE affects macrophages in specific tissues, we used surface markers F4/80 and CD11C to label intraperitoneal macrophages. The use of flow cytometry analysis demonstrated a notable upregulation of the F4/80 marker after FE administration. Tissue-specific macrophages help maintain homeostasis and trigger the immune system in response to stimuli. The expression of the integrin CD11C, which is abundant in monocytes and macrophages, was reduced when FE was injected, reaching levels comparable to the control group (healthy mice). Therefore, FE did not elicit a CD11C-mediated response, an indicator of macrophage activation. These observations suggest that administering FE reduced the inflammatory response when exposed to LPS stimulation.

The study confirmed the anti-inflammatory activity of the commercially available fucoidan extract and suggested that it may be worth considering large-scale production for use in clinical settings.

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Source: Mar. Drugs 2023, 21(5), 302; https://doi.org/10.3390/md21050302