Endothelial cells, found as a single layer lining the luminal surface of blood vessels, play crucial roles in maintaining vascular tone, preventing the formation of intravascular thrombus, and safeguarding against the onset of arteriosclerosis.

When endothelial cells are exposed to strong contractile substances, they produce and release factors that exhibit strong vasodilatory effects (NO, prostacyclin, hyperpolarizing factors) and antagonize the contractile effects. Decreased function or detachment of endothelial cells can lead to the occurrence of several cardiovascular diseases. These diseases include blood clots, promotion of blood coagulation, arteriosclerosis, peripheral blood circulation disorders, spasms of coronary and cerebral blood vessels, and an elevation in hypertension levels. Recent studies suggest that fucoidan, a sulfated fucose-rich polysaccharide derived from brown algae, exhibits multiple promising biological effects, including anti-inflammatory properties.

Hence, in this blog, I would like to share a wide study, “Impact of Enzymatically Extracted High Molecular Weight Fucoidan on Lipopolysaccharide-Induced Endothelial Activation and Leukocyte Adhesion” by Nora Kirsten et al. The primary focus of the study was to examine the impact of high molecular weight (HMW) fucoidan extracts derived from Fucus vesiculosus on the activation of endothelial cells and their interaction with primary monocytes (MNCs) in the context of inflammation induced by lipopolysaccharide (LPS).

First, in this study, they investigated the effects of high molecular weight (HMW) fucoidan extracts on endothelial cell activation and interaction with primary monocytes (MNCs) during lipopolysaccharide (LPS)-induced inflammation. Their initial investigation revolved around investigating how purified high molecular weight fucoidan fractions derived from Fucus vesiculosus (FV_crude) (specifically FE_FE1, FE_FE2, and FE_F3) impacted endothelial activation in an in vitro setting. A mild enzyme-assisted extraction combined with ion exchange chromatographic fractionation resulted in a well-defined and pure fucoidan fraction. In order to explore its anti-inflammatory potential, a molecule called FE_F3 was chosen, which has a molecular weight ranging from 110 to 800 kDa and a sulfate content of 39%.

The results of the study showed that when they had tested two different concentrations, the researchers observed a decrease in the inflammatory response of both endothelial cultures alone and co-cultures with MNCs as the purity of the fucoidan fraction increased in a dose-dependent manner. The experimental findings indicated a notable decline in IL-6 and ICAM-1 at both the gene and protein levels, as illustrated in Figure 1 A. Additionally, it was observed that the administration of all fractions resulted in an elevation of ICAM-1 protein levels. However, treatment with purer fractions (FE_F2, FE_F3) results in a lower increase in ICAM-1. It can be concluded from this experiment that the fucoidan fractions FE_F2 and FE_F3, which are purer in composition, do not elicit inflammatory activation in endothelial cells. This finding was observed in multiple donors, as depicted in Figure 1C. FE_F3 was found to be the fraction with the most promising efficacy and highest purity.

In order to examine the impact of fucoidan on the inflammatory response of LPS-stimulated OECs, the further study conducted a quantitative analysis of the expression levels of various inflammatory mediators including IL-6, NF-kB, TLR4, GSK3β, as well as adhesion molecules such as ICAM-1, VCAM-1, and E- Did. For a period of 5 days, OECs were subjected to treatment with different doses of fucoidan extract. Subsequently, these cells were further stimulated with LPS for 2 days, while the fucoidan treatment was maintained throughout this period. The expression of IL-6 was downregulated after FE_F3 treatment, whereas treatment with LPS alone significantly increased IL-6 expression in OECs compared to untreated control cells. Both FV_crude and FE_F3 extracts decreased the gene levels of NF-kB and TLR4 in LPS-stimulated OECs. The results of the study show that pretreatment with FV_crude and FE_F3 has the potential to decrease LPS-induced endothelial activation in monocultures of OEC.

An alternative way to approach the study of the anti-inflammatory bioactivity of fucoidan is by examining the involvement of TLR4. Monocytes and macrophages are known to acquire resistance to LPS by downregulating TLR4, leading to decreased inflammatory cytokine production. Therefore, in the study, they observed that the gene expression of TLR4 decreased after fucoidan treatment. The decreased gene expression of TLR-4, GSK3β, and NF-κB provided evidence for this.

In conclusion, these data indicate that the anti-inflammatory effect of fucoidan increases with its purity and suggests that fucoidan may help limit the inflammatory response of endothelial cells in LPS-induced bacterial infections.

Source: Mar. Drugs 2023, 21(6), 339; https://doi.org/10.3390/md21060339