Study on the alleviating effect of fucoidan on oxidative stress in rats
During normal physiological activities, the body produces an appropriate amount of reactive oxygen species (ROS) to participate in immune responses and information presentation processes. At the same time, there is also a mechanism in the body that inhibits ROS reactions, which can clear excess ROS and maintain the balance of the body’s physiological state. If the body’s antioxidant function is disrupted and stimulated without timely clearance of increased ROS, it will damage the body’s biological macromolecules such as nucleic acids, proteins, phospholipids, sterols, and fats, causing oxidative stress reactions. Normal cells in the body have a large number of enzyme and non enzyme endogenous defense systems to resist ROS invasion. For example, enzyme systems such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) present in animal bodies convert ROS such as O2- · and H2O2 into molecular oxygen and water. Research has found that exogenous natural antioxidants help alleviate oxidative stress-induced damage in the body by improving intracellular enzymatic and non enzymatic systems. Most natural antioxidants are isolated from vegetables, fruits, and herbal plants, and recently, fucoidans isolated from marine organisms, especially seaweed, also have potential antioxidant activity.
Fucoid polysaccharides are a complex mixture of heterologous natural polysaccharides, mainly composed of L-fucose and sulfate groups, as well as small amounts of various forms of proteins, monosaccharides, uronic acids, and acetyl groups. Research has shown that the content and sites of sulfate groups, the main active groups of fucoidan from different sources, vary. Sulfate groups are mainly located at the C2, C4, or both positions of fucoidan residues, occasionally also at the C3 position, which greatly affects the activity and effectiveness of fucoidan. In recent years, research has shown that fucoidan has many biological activities, such as anticoagulant, antibacterial, antiviral, anti obesity, anti-tumor, anti arthritis, neuroprotection, immune regulation, and protection of intestinal barrier function. Research has shown that fucoidan exhibits excellent antioxidant activity both in vivo and in vitro. In addition, fucoidan also exerts biological activities such as preventing gastric ulcers, promoting wound healing, and neuroprotection through its antioxidant function.
The above results indicate that fucoidan is a potential natural antioxidant and has the potential to be developed as a natural antioxidant for use as a food additive. Based on this, this experiment established an oxidative stress rat model by intraperitoneal injection of Diclofenae and fed it with fucoidan to study the alleviating effect of this natural antioxidant on oxidative stress.

In normal animal organisms, the production and clearance of ROS is a dynamic equilibrium process. When there are drastic changes or excessive stress in the internal and external environment, it can lead to a large accumulation of ROS in the body, which can easily cause cell death or tissue damage, thereby affecting the normal life activities of animals. The liver is an important metabolic organ in the body, and the spleen is an important immune organ. Various chemical reagents and drugs can cause damage to the liver and spleen, and even pathological damage. Oxidative stress is commonly present in various liver and spleen diseases, and ROS plays an important role in the pathogenesis of liver and spleen diseases induced by multiple factors. The synthesis and secretion of ALT and AST by the liver are important indicators for evaluating liver function. When liver cells are damaged, ROS produced can damage cell membranes and organelles, causing liver cells to swell or even die, leading to the release of ALT and AST from cells into the bloodstream and an increase in serum ALT and AST activity. This study found that oxidative stress induced by Diclofenae increased serum AST activity in rats, while oxidative stress led to an increase in serum total bilirubin levels. In addition, oxidative stress reduces the weight of the liver and spleen in rats, indicating that oxidative stress induces damage to the liver and spleen. Preventing ROS generation and lipid peroxidation is the most common mechanism of natural liver protective compounds. In recent years, fucoidans isolated from various seaweeds and some marine invertebrates have been shown to be potential ROS scavengers, with a certain alleviating effect on oxidative stress in the body, and have the potential to exert liver and spleen protective effects through antioxidant activity. Research has shown that treatment with fucoidan significantly inhibits the elevation of serum ALT and AST activity induced by acetaminophen (APAP), cyclophosphamide, alcohol exposure, CCl4, and D-galactosamine+lipopolysaccharide in mice, and has a good protective effect on liver damage. Consistent with the above results, feeding rats with fucoidan significantly reduced serum AST activity, indicating that fucoidan can effectively alleviate liver damage in rats.
In addition, oxidative damage may lead to excessive consumption of antioxidant enzymes in the body, or inhibit the synthesis and activation of antioxidant enzymes, exacerbating oxidative damage in the body. In this study, after intraperitoneal injection of Diclofenac, the levels of GSH, CAT, SOD, and GPx activities in liver tissue were significantly reduced, and the activities of CAT, SOD, and GPx in spleen tissue were also significantly reduced. This indicates that oxidative stress leads to the depletion of CAT, SOD, GPx, and GSH in the body, a decrease in antioxidant capacity, excessive oxidation of cell membrane lipids, and an increase in MDA content. And pretreatment with fucoidan significantly alleviated the decrease in SOD and GPx activity after intraperitoneal injection of Diclofenae, enhanced the overall antioxidant capacity of the body, and reduced lipid peroxidation. In summary, feeding fucoidan can enhance the antioxidant capacity of rat liver and spleen. Similarly, fucoidan increased GSH levels in APAP treated mouse liver tissue and increased SOD and CAT activities, thereby inhibiting ROS and MDA levels. Tian et al.’s research also showed that fucoidan increased the activities of SOD, GPx, and CAT in mouse liver, reduced MDA levels, and alleviated cyclophosphamide induced liver damage in mice. Fucoidan polysaccharides can also effectively alleviate the decrease in serum SOD and GPx activity, reduce MDA content, and inhibit lipid peroxidation caused by ROS in CCl4 and D-galactosamine+lipopolysaccharide induced liver injury mouse models, thereby protecting the liver. In addition, fucoidan also reduced the increase in NO content in rat kidney tissue induced by cyclosporine A, increased spleen GSH content, reversed the inhibitory effect of cyclosporine A on SOD activity, and thus improved kidney tissue damage. These results indicate that fucoidan can alleviate lipid peroxidation and oxidative damage in the body by increasing the activity of antioxidant enzymes.
There are multiple oxidative stress pathways in animal bodies, one of which is the Keap1 (Kelch like epichlorohydrin associated protein-1) – Nrf2 ARE (antioxidant response element) signaling pathway. When cells are not stimulated, the inhibitory proteins Keap1 and Nrf2 bind to form a complex, which isolates Nrf2 separately in the cytoplasm. When the body is exposed to stressors or inducers, Nrf2 undergoes phosphorylation at its specific serine or threonine site, and Nrf2 separates from the Keap1/Nrf2 complex and migrates into the nucleus. Subsequently, Nrf2 binds to ARE and regulates the expression of a series of downstream protective genes that encode intracellular detoxifying enzymes, including HO-1, quinone oxidoreductase 1 (NQO1), glutathione S-transferase (GST), CAT, SOD, and GPx, which increase the cell’s ability to clear ROS. Research has found that fucoidan can alleviate oxidative damage in the body by regulating the Nrf2 signaling pathway. Feeding fucoidan can upregulate the decrease in Nrf2 expression induced by dimethylnitrosamine in rat liver tissue, upregulate the transcription of genes such as GST, NQO1, and SOD, thereby increasing the activity of SOD and GPx in liver and serum, and alleviating the degree of lipid peroxidation in the body. Research has found that fucoidan can also increase the levels of Nrf2, HO-1, glutamate cysteine ligase (GCLM), and NQO1 protein by upregulating the Nrf2/HO-1 pathway, thereby enhancing the activities of CAT, SOD, and GPx in the liver and kidneys, reducing MDA levels, and improving cyclophosphamide induced liver and kidney damage in ICR mice. There are also studies showing that fucoidan enhances the expression of total Nrf2 in liver tissue and Nrf2 in the nucleus, increases SOD and CAT activity and GSH content, and alleviates the increase in ROS and MDA levels induced by APAP in liver tissue. The above results indicate that the liver protective mechanism of fucoidan is related to Nrf2 mediated oxidative stress. fucoidan effectively stimulates Nrf2 translocation from the cytoplasm to the nucleus, enhances the body’s antioxidant capacity, and inhibits ROS accumulation. Consistent with the above viewpoint, in this experiment, oxidative stress inhibited the gene expression of Nrf2 in rat liver and spleen tissues, and downregulated the gene expression of downstream CAT, SOD1, SOD2, and GPx. Feeding fucoidan up-regulated the gene expression of Nrf2, GPx, and SOD2 in liver and spleen tissues, indicating that fucoidan activates the Nrf2 signaling pathway and downstream antioxidant enzymes such as SOD and GPx, thereby exerting antioxidant effects and inhibiting oxidative damage in the body.
In summary, fucoidan upregulates the expression of antioxidant enzyme genes and regulates antioxidant enzyme activity in rat liver and spleen tissues through the Nrf2 pathway, thereby alleviating oxidative stress response in rats.