Relationship between Polysaccharides Structures and Their Bioactivities: History
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Contributor:
Elda A. Flores-Contreras
,
Rafael G. Araújo
,
Arath A. Rodríguez-Aguayo
,
Muriel Guzmán-Román
,
Jesús Carlos García-Venegas
,
Erik Francisco Nájera-Martínez
,
Juan Eduardo Sosa-Hernández
,
Hafiz M. N. Iqbal
,
Elda M. Melchor-Martínez
,
Roberto Parra-Saldivar

Brown macroalgae polysaccharides are known for their several potential therapeutic properties; in fact, they are used as an ingredient or component in a wide range of industries, including pharmaceutical, medical, food, and cosmetics. The most promising activities are in the field of medicine due to their antiviral, anti-inflammatory, antioxidant, and anticarcinogenic actions.

  • brown macroalgae
  • bioactivity
  • biopolymer
  • extraction methods
  • fucoidan

1. Anticancer Activity

Cancer is considered the main cause of death worldwide; in 2021, more than 10 million people died from this disease. Cancer is defined as a malignant tumor or neoplasm of abnormal tissue mass, which has the potential to metastasize and attack any part of the body with a high risk of death [1]. Therefore, research and science have been focused on developing precise and effective alternative techniques to reduce cancer’s impact on health and improve conventional treatments. New technologies using nanomedicine and biomaterials are under evaluation in clinical trials and others are already in clinical practice [2]. Biocompatible materials have been promising elements because they can be bioengineered in different forms as nanoparticles with important advantages, such as selectivity and efficacy in the attack on tumor cells [3].
Several researchers around the world have been promoting and reporting the anticancer activity of brown algae and the behavior of cancer cell lines in in vitro assays. One study reported the anticancer activity of laminarin by using L. japonica at a concentration of 35 mg/mL to significantly decrease the Bel-7404 (human hepatoma cell line) viability; for 48 h, the viability was only 46.20%, and for HepG2, it was only 42.85%. Regarding the apoptosis rate for the Bel-7404 cell line, it was 2.72 higher with laminarin, and for HepG2, it was 8.18 times higher than without treatment (Table 1) [4].
The bioactivity of fucoidan has been widely used due to its inherent anticancer properties, favorable drug delivery behavior, and promising targeting ability, resulting in the induction of cell apoptosis and inhibition of angiogenesis [5]. For example, in some species of brown seaweed, such as Turbinaria conoides, the anticancer effect on the hepatoblastoma-derived (HepG2) cell line has been studied through a cell viability assay, using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MTT and different concentrations (0–200 μg/mL) of fucoidan/quercetin treatments for 48 h. The results show that the fucoidan/quercetin treatment reduced cell viability to less than 50% in a concentration-dependent manner. A concentration of 200 μg/mL demonstrated a better performance. The results conclude that fucoidan had more significant anticancer activity compared to quercetin [6].
On the other hand, alginate has not been as widely used in anticancer activity as other brown algae polysaccharides, even though some reports of the cytotoxic effects alone or in combination with different compounds have demonstrated the potential that alginate could contribute to cancer treatments. A study using polysaccharides from brown algae C. Sinuosa showed the bioactivity of alginate by promoting a significant decrease in the cell viability of HCT-116 cells, with an IC50 of 690 μg/mL−1 and a 37.1% inhibition rate at 750 μg/mL−1. Nevertheless, fucoidan at similar high concentrations resulted in a better inhibition rate of 45% [7]. Alginate can play a major role in encapsulation as alginate-based hydrogels for cancer therapy, which can control and target drug administration, improving the stability and minimizing unwanted effects, time, and effort [8][9]. Recent research has reported that low-weight alginate oligosaccharides have better anticancer activity than complete polysaccharide because they prevent cancer cell proliferation and reduce tumor metastasis, in addition to providing antioxidant and anti-inflammation properties [10].
Table 1. Biomedicine and therapeutic applications of polysaccharides from brown algae species.
Brown Algae Polysaccharide Bioactivity Bioassay Bioactivity Results Reference
L. japonica Laminarin Anticancer Cell viability detected by WST-8 cell proliferation assay, flow cytometry in 96-well plate in human HCC cell lines, including Bel-7404 and HepG2, when incubated with different concentrations of laminarin. Hepa 1–6 tumor-bearing mice were injected with different concentrations and tumors were measured. Cell viability;
;aminarin concentrations of 35 mg/mL significantly decreased the Bel-7404 viability, with only 46.20% at 48 h.
HepG2 was only 42.85% of that of cells without treatment. Apoptosis rate of Bel-7404 was 2.72 higher with laminarine and 8.18 times higher for HepG2 than without treatment.
Tumor growth inhibition was higher at 1200 mg/k.d of laminarin with 67.92%.		 [4]
Padina pavonioca Sulfated polysaccharides Anticancer Antioxidant DPPH
Cell viability: MTT assay cytotoxic activity in HeLa cancer cell lines cultured in DMEM supplemented.		 A total of 1 mg/mL increases scavenging activity up to 63%.
Low doses (0.05–0.1 mg/mL) exhibit cytotoxic activity in HeLa cancer cell line.		 [11]
Sargassum ilicifolium Fucoidan Antioxidant Osteogenic ability (bone regeneration) DPPH expression of osteoblast differentiation media in DMEM supplemented with murine mesenchymal stem cells (C3H10T1/2). IC50 0.96 mg/mL (crude) and 2.51 mg/mL (purified).
A total of 1 μg/mL of purified fucoidan provides cell proliferation (130%) on C3H10T1/2 at 48 h.		 [12]
Silvetia Compressa
Ecklonia arborea		 Sulfated polysaccharides (fucoidan, laminarin, alginate) and phlorotannins Antioxidant DPPH & ORAC DPPH IC50 (mg/mL)
S.Compressa 1.7
E. arborea 3.7
ORAC (mmol Trolox equivalent/g) S.Compressa 0.817
E. arborea 0.801.		 [13]
Sargassum siliquosum Fucoidan Antioxidant Anti-inflammatory DPPH (absorbance of 50% methanol solution mixed with the sample solution was the blank). Cell viability: RAW264.7 cell line in 24-well plate. TNF-α content level after lipopolysaccharide LPS exposure reflected the anti-inflammatory activity. Quercetin was used as a positive control. Antioxidant results: EC50 of purified fucoidan 2.58 mg/mL, higher antioxidant ability showed crude extract with an EC50 of 0.34 mg/mL. Cell Viability: Inhibition of TNF-α reached 14.8% with 0.25 µg/mL of fucoidan-treated compared to LPS control. [14]
Sargassum horneri Alginic acid Anti-Inflammatory Cell culture RAW 264.7 mouse macrophages and HaCaT (human keratinocytes) cultured in DMEM, 10% FBS, and 1% antibiotics. In 24-well plates, HaCaT were seeded with SHA and Chinnese fine dust CFD at 125 µg/mL under optimized conditions. MTT assay was used for cell viability. Cell viability: A concentration of SHA 25–100 µg/mL decreased viability of HaCaT in a range of 20%. [15]
Sargassum horneri Fucoidan Anti-inflammatory Cell culture and viability assay
RAW 264.7 macrophages were cultured in DMEM, 10% FBS, and 1% antibiotics. MTT test in 24-well plate. Negative control had untreated macrophages, positive control was only treated with PBS.		 Fucoidan in concentrations of 12.5–50 μg/mL inhibited the production in LPS-activated RAW 264.7 macrophages with IC50 = 40 µg/mL. [16]
Sargassum fulvellum Sulfated polysaccharides Anti-inflammatory Anti-inflammatory activity in RAW 264.7 macrophages cultured in DMEM medium. Stress induced by E. coli lipopolysaccharides. In vivo tests applied in zebrafish embryos to measure their survival rate after 3 days. Levels of ROS, heartbeat, and cell death after stress induced by E. coli lipopolysaccharides. Viability of RAW 264.7 cells increased by 94.6%, while the production of nitric oxide (NO) in RAW 264.7 decreased by 40.7%. Zebrafish survival, cell death, and ROS/NO production decreased in a dose-dependent manner. [17]
Turbinaria decurrens Fucoidan Anti-inflammatory Swiss albino mice were subjected to formalin-induced paw edema. The mice were treated with the extracted fucoidan, which was administered orally, to evaluate the anti-inflammatory effect. The mice treated with fucoidan showed reduction in the perception of the wound by the mice. The licking time was reduced by more than 50%. In addition, the anti-inflammatory effect of the fucoidan in paw edema showed a reduction of 52%. [18]
Sargassum fusiforme Sulfated polysaccharides Anti-inflammatory Sulfated polysaccharides extracted by an enzymatic method were tested in RAW 264.7 cells stressed with lipopolysaccharide (LPS). To study the anti-inflammatory effects of the polysaccharides, the level of expression of NO and inflammatory cytokines, such as TNF-α, IL-1β, IL-6, and PGE2, were determined. The sulfated polysaccharides showed an anti-inflammatory activity with a dose-dependent behavior. The addition of the polysaccharides successfully reduced the expression of TNF-α, IL-1β, IL-6, and PGE2. Additionally, the production of NO was reduced, while the cellular viability increased. [19]
L. japonica Polysaccharides Antiviral The polysaccharides isolated by ethanol precipitation were tested in HEK293 cells infected with the respiratory syncytial virus (RSV) to study the antiviral activity of the polysaccharides. The expression of IRF3 and IFN-α were analyzed. The polysaccharide extracts demonstrated significant antiviral activity against RSV by increasing IFN-α expression via regulation of the IRF3 signaling pathway in HEK293 cells. [20]
Sargassum polycystum Fucoidan fraction-2 (Fu-F2) Antibacterial The MIC and MBC were determined for bacterial strains Streptococcus mutans, Staphylococcus aureus, Pseudomonas aeruginosa, and E. coli. A 48-well microtiter plate was used. The antibacterial activity was determined by disk diffusion assay. Test bacteria were grown on Luria-Bertani agar medium and a crude fucoidan loaded disk was placed with the standard antibiotic disk (tetracycline). The highest antibacterial activity (21 ± 1.0 mm) was obtained at 50 µg/mL against Pseudomonas aeruginosa, and the lowest activity (16 ± 0.53 mm) was against Staphylococcus aureus. [21]
Fucus vesiculosus Fucoidan Anti-angiogenesis Use of crude extracted fucoidan over endothelial cells and chicken embryos. A concentration of fucoidan at 0.5 mg/mL was able to prevent the formation of tubular structures in epithelial cells. Chicken embryos presented a reduction in blood vessel formation, as well as in the tumoral mass. [22]
Fucus distichus subsp. evanescens Fucoidan Anti-angiogenesis Measurement of the gene expression of the angiopoietins 1 and 2, vascular endothelial growth factors, and stromal-derived factors in mono- and co-cultured systems of human outgrowth endothelial and human mesenchymal stem cells. Cells were treated for seven days with extracts obtained enzymatically from Fucus distichus subsp. evanescence. The anti-angiogenic activity of co-cultured cells was analyzed by measuring the length and area of the tube-like structures created by the endothelial and mesenchymal cells. In monoculture: The fucoidan extract downregulates the expression of vascular endothelial growth factor and stromal-derived factor-1 in mesenchymal stem cells; however, the angiopoietins-1 and angiopoietins-2 in the outgrowth endothelial cells’ levels were not affected by the fucoidan extract. The fucoidan extract with the higher sulfate content was able to disturb the formation of the tube-like structures; length and area were both reduced. [23]
Ascophyllum nodosum Sodium alginate Prebiotic Alg-MAE (microwave-assisted extraction) L. delbruecki ssp. bulgaricus and L. Casei growth media. Inulin (positive prebiotic control), glucose (the negative control in a 96-well-plate. Alg- MAE improved the growth rate of L. delbruecki ssp. bulgaricus by 75% (at 0.10% (w/v) inclusion), 150% (at 0.50% (w/v)), 40% (at 0.10% (w/v)), and 34% (at 0.30% (w/v)) for L. casei when compared to the unsupplemented media. [24]
Sargassum glaucescens Fucoidan Hair growth-promoting (alopecia treatment) Cell proliferation: Human follicle dermal papilla cells (HFDPC) in DMEM with 1% FBS for 24 h, then treated with different molecular weight fucoidans (HHP-1-MW, SCW-1, and SCW-5; 1 mg/mL). HFDPC treated by glucose (1 mg/mL) as control; cell viability was measured with CCK-8 assay. Hair follicle culture assay: 5-week-old male C57BL/6 mice. Cultured in William’s medium with or without the supplementation of SCW-5 (1 mg/mL) or minoxidil (1 µM). Cell proliferation was higher than glucose or PBS treated control. SCW-1 was the most effective with cell viability (200%) of HFDPC. The hair follicles treated by SCW-5 after 69 days of treatment had better hair growth than the minoxidil and control groups (p < 0.05). [25]
Sargassum angustifolium Fucoidan Wound healing The wound healing effect of crude fucoidan extracts on adipose-derived mesenchymal stem cells (ADMSCs) was determined by MTT and scratch assays. The crude extracts of fucoidans were demonstrated by the MTT assay to improve growth up to 1.5 times. With the scratching technique, an increase in cell migration of 76 and 142% was observed after 48 and 72 h of incubation, respectively, in ADMSC cells. [26]

2. Antioxidant Activity

Reactive oxygen species (ROS) are involved in biological reactions and intracellular signaling pathways. They are normal products derived from metabolism, such as hydroxyl radicals (OH•), superoxide radicals (•O2−), peroxyl radicals (ROO•), peroxide organics (ROOR’), peroxynitrite (ONOO−), and hydrogen peroxide (H2O2). However, a major problem is caused when oxidative stress is present due to the abnormal proliferation of ROS, which has the potential to induce damage in cells in a significant range; vital biomolecules, such as DNA, proteins, and lipids, among others, are affected by oxidative stress and can cause serious diseases, including neurodegeneration diseases, cancer, arthritis, and atherosclerosis [10][27]. Thus, scientists have been searching for years for potential solutions, such as antioxidants that have a significant role in inhibiting oxidation reactions caused by ROS.
Nowadays, it is known that synthetic antioxidants have generally been used in the food industry as additives. Their long-term use produces side effects, bringing notable attention to natural antioxidants. Algal extracts from different species have demonstrated a crucial opportunity to contribute to this sector; in fact, more than fifty species of brown algae from around the globe have been reported to show significant antioxidant activities [28]. The main bioactive compounds with antioxidant activity in brown seaweed species are phlorotannin, fucoxanthin, and polysaccharides, such as alginic acid, fucoidan, and laminarin. These have been studied extensively due to the interest in their potential implementation in pharmaceuticals [29].
Laminarin presents potential antioxidant activity, especially against oxidative stress caused by ROS and free radicals. Crude laminarin extract from brown algae L. hyperborean has exhibited higher DPPH radical scavenging (38.62%) compared to commercial laminarin standard (13.93%) from SigmaTM (Sigma-Aldrich, St. Louis, MO, USA). These results agree with the theory that the polysaccharides’ structures have antioxidant activity [30]. In vivo trials have been reported, usually in rats and porcine, to demonstrate the potential effect of laminarin in pulmonary and lipid oxidations, in addition to increased natural antioxidant properties and mitigating ROS generation [31].
Fucoidan antioxidant assays have been applied alone and combined with other sulfated polysaccharides. Fucoidan from C. Sinuosa displayed a high antioxidant capacity in 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and superoxide dismutase (SOD) assays, showing remarkable scavenging activity of 89% at 750 μg/mL−1, DPPH IC50 of 46.2, and SOD IC50 23.7 [7]. Sulfated fucoidan of Sargassum polycitum has also demonstrated antioxidant behavior using the ferric reducing antioxidant power (FRAP) method; the results of IC50 of 41,667 ppm show intense activity [32]. Other recent fucoidan antioxidant results demonstrating the activities of Sargassum ilicifolium, Silvetia Compressa, and Sargassum siliquosum are described in Table 1.
Alginate has been widely used as an antioxidant agent, including as a crude extract, combined, and even as base material for encapsulation. The polysaccharide has indicated an ability to scavenge free radicals and reduce ROS disorder. Favorable antioxidant results of alginate alkaline treatment have been reported in a range from 35.83 to 120.48 μMTEg−1 and temperature stable up to 50 °C, decreasing in the temperature range of 70–100 °C [33]. However, recent studies have suggested that alginate oligosaccharides have a better and significant enhancement in antioxidant activities and the capacity to protect endothelial cells, providing a possible therapeutic application for atherosclerosis and related diseases [17].

3. Anti-Inflammatory Activity

External stimuli, such as injuries or the appearance of pathogenic microorganisms, as well as internal stimuli, such as stress that is considered harmful for any living system, trigger the natural response of inflammation. The inflammatory reaction includes the activation of the immune system, particularly the macrophage and neutrophil cells, which, during the inflammation process, generate secondary factors, such as pro-inflammatory cytokines, nitric oxide (NO), and prostaglandin E2 (PGE2) [34]. The cytokines known as interleukin-1B (IL-1B), interleukin 6 (IL-6), tumor necrosis factor (TNF-alfa), and interleukin-12 (IL-12), as well as enzymes, such as cyclooxygenase (COX-2) and matrix metalloproteinase-9 (MMP-9), are global biomarkers of inflammation [35][36][37].
The biopolymers from brown macroalgae have shown strong anti-inflammatory activities in in vitro and in vivo models. Wang et al. [17] obtained a rich sulfated polysaccharide extract from the Sargassum fulvellum and tested its anti-inflammatory properties against RAW 264.7 macrophages and zebrafish embryos stressed by E. coli lipopolysaccharides. The extract was able to increase the cell viability of the macrophages up to 94.6%, while the levels of NO, PGE2, TNF-alfa, and interleukins 1 and 6 decreased significantly (Table 1). In a similar way, the zebrafish embryos treated with the sulfated polysaccharides increased their survivability by 70%; in addition, the NO levels, the reactive oxygen species, and the overall cell death was reduced as an effect of the sulfated polysaccharides. Both in vivo and in vitro experiments showed a concentration-dependent behavior, and the best results were obtained with the higher polysaccharide concentration of 100 µg/mL. Another study by Manikandan et al. based on an in vivo model reported high anti-inflammatory activity from a fucoidan extracted from brown algae [18]. They used fucoidan extracted from Turbinaria decurrens to explore its activity against formalin-induced paw edema in Swiss albino mice. Their results demonstrate that the polysaccharide administered orally was able to reduce the licking time of the mice of the paw edema by more than 55%, meaning it reduced the mice’s perception of the wound. In addition, the inflammation of the paw edema was reduced by 52% utilizing the standard treatment drug called dexamethasone. An analysis of the paw tissues of the mice reported a reduction in the expression of the COX-2, IL-1B, and MMP-9 genes in comparison to the gene’s expression of the untreated mice with induced paw edema. A study exploring the anti-inflammatory activity of polysaccharides from brown algae was made by Wang et al. [14]: they extracted sulfated polysaccharides from the Sargassum fusiforme by an enzymatic method and tested the extracts on LPS-induced stress RAW 264.7 macrophages. The anti-inflammatory activity was analyzed by reading the level of expression of common inflammatory factors, such as NO, TNF-α, IL-1β, IL-6, and PGE2. The sulfated polysaccharides were able to decrease the level of expression of these markers in a dose-dependent behavior; in addition, the cellular viability was enhanced as a result of the reduction of the NO levels.

4. Antiviral Activity

Viral infections have caused a severe burden on public health around the globe, especially with the pandemic caused by SARS-CoV-2. Viruses are divided into two types: simple (or non-enveloped), which are made up of nucleic acid and a protein capsid, and complex (enveloped), which have a lipoprotein envelope over the protein capsid, making them stronger to protect against environmental factors and conferring protection from viruses to disinfectants or antiviral agents. Nevertheless, to reduce collateral effects from synthetic drugs, pharmacology has been searching for and developing novel, natural, and antiviral agents in order to help alleviate symptoms, shorten the disease period, and minimize side effects and toxicity [38]. Recently, it has been reported in several studies that the antiviral properties of sea life is not only limited to polysaccharides from brown algae, but can also be found in sea cucumber, navicula, green algae, blue–green algae, red algae, and even in chondroitin sulfate from sharks. Recent research indicates the capacity to mitigate viruses by preventing them from interacting with host cells, inhibiting RNA replication and protein synthesis [39].
In this sense, a wide range of studies has been reported on alginate-based materials to verify the antiviral properties of more than 15 types of viruses that can infect different organisms. Alginic acid has been tested against the rabies virus in chicken embryo-related cells, showing a dose-dependent inhibitory effect from 1 to 100 μg/mL. Sodium alginate has also inhibited potato virus X by 95% using Chenopodium quinoa as a host; a strong antiviral effect was demonstrated at a concentration of 1 μg/μL [40]. Furthermore, these previous studies led to research lines for alginate-based biomaterials against SARS-CoV-2.
Laminarin acts by promoting the humoral immune response of virus-infected host cells and activating natural killer (NK) cells and T-lymphocytes [41]. Therefore, laminarin isolated from brown seaweed could be a source of new alternatives against HIV. Shi et al. [42] used a concentration of 50 mg/mL and demonstrated low cytotoxicity; furthermore, they were able to block the adsorption of the virus and suppress the reverse transcriptase. Additionally, other authors have found a positive antiviral response from the laminarin of L. japonica against respiratory viruses, such as H5N1 and the RSV virus [20].
Fucoidan is the brown algae biopolymer with the largest spectrum of antiviral properties reported; nevertheless, its bioactive capacity depends on the large size chain, molar composition, and structural attributes, such as the molecular weight and chemical compositions, which can be affected by variations in the season and the specie [43]. There is a wide range of viruses that fucoidan can be inhibit as an antiviral, such as RNA and DNA viruses, including HIV, HSV1-2, ASFV, HTLV-1, MPMV, dengue virus, and cytomegalovirus. Moreover, fucoidan can regulate mitosis or cellular apoptosis due to its capacity to inhibit digestive enzymes and interrupt glucose absorption. It has been shown to have positive responses against HIV. Fucoidan from Sargassum henslowianum was used against the herpes virus (HSV-1 and HSV-2) and demonstrated an IC50 of 0.82–0.89 μg/mL by plaque reduction assay; it also showed 0.48 μg/mL against HSV-2 [44]. Recently, the antiviral action of fucoidan has been tested to determine its usefulness against the current pandemic; in fact, in vitro models have demonstrated efficacy against SARS-CoV-2, significantly inhibiting the effect of viral spike protein binding [45]. Fucoidan concentrations between 9.10–15.6 μg/mL have inhibited SARS-CoV-2 in vitro via S glycoprotein binding. In addition, some reports of comparations of different weights of fucoidan have been performed using Saccharina japonica in HMW (8.3 μg/mL), significantly better than LMW (16 μg/mL) [46][47].

5. Non-Conventional Activities

Besides the known variety of studied bioactivities of polysaccharides extracted from brown algae, these polysaccharides have recently been tested in new applications. The latest evidence proves that these polysaccharides are able to benefit the gastrointestinal tract, improve the angiogenesis process, soothe metabolic syndrome, and enhance bone health [48].
The process in which new blood vessels are formed from old blood vessels is known as angiogenesis. This process consists of four stages: (1) the vascular permeability rises, (2) the endothelial cells travel through the extracellular matrix, (3) the differentiation occurs, and finally, (4) the new vessels form and mature after a short time [49]. The failure of any part of this process can lead to metabolic and cardiovascular disorders, but most importantly, can also lead to the growth of carcinogenic cells and therefore to cancer and potential metastasis [50]. Brown macroalgae biopolymers have been used as a countermeasure for uncontrolled angiogenesis. Oliveira et al. [22] used a fucoidan extracted from Fucus vesiculosus to prevent the formation of new blood vessels in endothelial cells and in chicken embryos. The extracted fucoidan at a concentration of 0.5 mg/mL was able to prevent the formation of more tubular formations on epithelial cells and the presence of the platelet-derived growth factor (PDGF) was downregulated; this factor is necessary for the proper maturation of blood vessels. In addition, the cells treated with this fucoidan presented a tendency to aggregate instead of spreading and connecting with each other. The chicken embryos treated with the fucoidan presented a decrement of blood vessels and the tumoral mass, supporting the activity of fucoidan as a component to prevent tumor progression. Another similar experiment was conducted by Ohmes et al. [23]. They tested fucoidan extracted from Fucus distichus subsp. evanesces into mono- and co-cultured human outgrowth endothelial cells (OEC) and human mesenchymal stem (MSC) cells. The fucoidan was obtained by enzymatic extraction with cellulases and alginate lyases, then different concentrations of fucoidan were tested in the different cultures. The level of expression of different genes, such as angiopoietins-1 (ANG-1), angiopoietins-2 (ANG-2), vascular endothelial growth factor (VEGF), and stromal-derived factor 1 (SDF-1), were measured to analyze the anti-angiogenic properties of the fucoidan extracted, as well as the length and area of the tube-like structures formed by the co-culture of the cells. The fucoidan was able to downregulate the expression of all the genes in MSC; however, the ANG-1 and ANG-2 in the OEC did not decrease because of the fucoidan. The fucoidan extract was able to disrupt and decrease the length and area of the tube-like structures formed during the co-culture of both MSC and OEC cells, showing a strong bioactivity against angiogenesis.
In addition, several researchers have found a prebiotic effect on human intestinal microbiota in brown algae polysaccharides. This is because they are not digestible by hydrolytic enzymes and are fermented in the colon by Lactobacillus and Bifidobacterium, improving growth and decreasing the concentrations of pathogens. However, digestion affects the activity of algae polysaccharides, therefore it is essential to verify resistance to hydrolysis under in vitro conditions [51]. Okolie et al. [24] worked with sodium alginate extracted from Ascophyllum nodosum by different extraction methods. The prebiotic activity was demonstrated by the in vitro growth rate of the Lactobacillus delbruecki ssp bulgaricus strain in growth media supplemented at 0.10, 0.30, and 0.50% (w/v). It was shown that the activity level depends on the concentration compared to the medium without supplements as a control; it was also shown that there are no significant differences between the techniques of extraction methods. It is important to note that in vivo experiments have generally been performed on rats, pigs, and mice. Zheng et al. [52] reviewed many of these and reported studies for the three brown algae biopolymers that had shown the prebiotic effect, especially by the Bacteroides genus, which projects the great potential of these macroalgae biocomposites for functional foods and drugs.
Polysaccharides from brown algae have attracted particular attention in the biomedical field due to their unique properties, such as biocompatibility, biodegradability, non-toxic, non-immunogenic, moisture-retaining, swelling ability, and resembling the structure of the extracellular matrix. Over the last few decades, polysaccharides have been used in biomedical treatments, especially for drug delivery systems, wound healing, and tissue engineering using modern polymer-production technologies, such as 3D-bioprinting or electrospinning [53]. Wound healing consists of several overlapping phases that are intended to restore the anatomical structure and retrieve function of damaged skin. Tissue engineering aims to regenerate damaged tissue/organs using cells, growth factors, and scaffolds [54]. Biopolymers, such as alginate, collagen, and chitosan, are the most used raw material for scaffold manufacturing due to their good plasticity behavior, drug compatibility, and biodegradability; however, synthetic biomaterials improve mechanical properties [55]. Alginate-based biomaterials have been the most used brown algae biopolymer due to their superior capacity to form scaffolding materials, including hydrogels, microcapsules, foams, sponges, and fibers [56]. Iglesias-Metujo and García-Gonzalez designed 3D-printing aerogel scaffolds for bone regeneration in an alginate concentration range of 6–10 wt% and a CaCl2 concentration of 0.5 M. In this study, the authors added hydroxyapatite to preserve the geometry of the strands, while the structural stability and yielding scaffolds were improved. The alginate–hydroxyapatite scaffolds were highly porous; furthermore, they were able to attach and proliferate mesenchymal stem cells, in addition to presenting an enhancement of the fibroblast migration in damaged tissue, which supports the bone regeneration potential. There currently exists a wide range of commercial wound dressing products using sodium or calcium alginate in combination with bioactive compounds for specific applications in biomedicine, such as Algicell™, Integra LifeSciences Corp ™, Biatain™, Comfeel Plus™, and Nu-derm™, among others [57].

This entry is adapted from the peer-reviewed paper 10.3390/plants12132445

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