2.1. Food Industry

Macroalgae have been consumed since ancient times in many countries around the world, mainly in the Asian regions. Nevertheless, their consumption has increased in the last decades in western countries, which has been attributed to the high nutritional values of macroalgae and their health benefits [10,11]. Some of the most consumed macroalgae are nori or purple laver (Porphyra spp.), kombu (Laminaria japonica), wakame (Undaria pinnatifida), Hiziki (Hizikia fusiforme), or Irish moss (Chondrus crispus), which can be consumed in different food formats (salads, soups, snacks, pasta, etc.) [11,12]. Still, most of them are considered an innovative niche product. Macroalgae are also widely used in the food industry to produce phycocolloids (polysaccharides of high molecular weight composed mostly of simple sugars), mainly alginates, agars, and carrageenans, which are frequently used as thickeners, stabilizers, as well as for probiotics encapsulation, gels, and water-soluble films formation [6,13]. Furthermore, diverse molecules present in algae have been shown to exert several bioactivities, such as antioxidant, anti-inflammatory, antimicrobial, and antiviral effects. These bioactive compounds (mainly proteins, polyunsaturated fatty acids, carotenoids, vitamins, and minerals) may play important roles in functional foods (e.g., dairy products, desserts, pastas, oil derivatives, or supplements) with favorable outcomes on human health [14]. Other applications of algae in the food industry include their use as colorant agents and the extraction of valuable oils (such as eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid) [15].

2.2. Biofuel

The development of algal biofuels (“third-generation biofuels”) has been considered an option to reduce the use of petroleum-based fuels and avoid competition between food and energy production for arable soil, since macroalgae grow in water. These organisms do not contain lignin, thus they are good substrates for biogas production in anaerobic digesters, while fermentable carbohydrates are fit for bioethanol production. Although the production of bioenergy from macroalgae is not economically feasible nowadays, several measures have been proposed to achieve a rational production cost in the future [16]. On the other hand, microalgae are considered a more suitable source to produce biodiesel due to the greater ease of controlling the life cycle and increasing the reproduction rate [17]. Microalgae biomass can be used for electricity generation or biofuel production after the lipid extraction. It has shown 80% of the average energy content of petroleum. The lipid content is highly dependent on the microalgae species and the cultivation conditions, thus not all species will be profitable, and choosing appropriate microalga strain is crucial [18]. Some microalgae used to produce biofuel are Chlorella spp., Dunaliella salina, Haematococcus pluvialis, Spirulina platensis, Porphyridium cruentum, Microcystis aeruginosa, and Scenedesmus obliquus [19].

2.3. Therapeutic and Cosmetic Products

The use of macroalgae for therapeutic purposes has a long history, but the search for biologically active substances from these organisms is quite recent. Numerous studies have demonstrated the biological properties of macroalgae extracts and compounds, including antioxidant, anti-inflammatory [20], antithrombotic, anticoagulant and coagulant [21], antimicrobial [22], and anticancer [23]. In addition, macroalgae have been demonstrated to exert biological properties applicable to cosmetic products, such as photo-protection, anti-aging, or anti-cellulite (Table 1). Considering this range of activities, macroalgae extracts and compounds have been considered for different pharmacologic and cosmetic products [24]. Regarding cosmetics, brown and red seaweeds are usually employed. The interest of these species lies in their content in cosmeceuticals ingredients, such as phlorotannins, polysaccharides, and carotenoid pigments [25]. These compounds are incorporated into cosmetics due to their bioactivities, their capacity to improve organoleptic properties, and their capacity to stabilize and preserve the products [26].

2.4. Fertilizer and Animal Feed

Currently, the negative environmental impacts of synthetic fertilizers have been identified. Thus, the use of organic fertilizers, including macroalgae, has been proposed as a suitable alternative to reduce the impact on the environment [45,46]. In fact, macroalgae have been used since ancient times as fertilizers, and several beneficial effects have been described, such as enhancement of crops growth and yield, increased resistance against abiotic and biotic stresses, or nutrient intake [46,47,48]. The biostimulant effects of macroalgae have been attributed to diverse biological compounds such as plant hormones, phlorotannins, and oligosaccharides [48].

Regarding animal feed, macroalgae have been employed for this purpose since ancient times as feed but also as nutritious supplements [49]. Several studies have evaluated the positive effects of macroalgae-enriched food, both for terrestrial animals [50] and specially in aquaculture animals [51,52,53,54].

3.1. Polysaccharides

In the case of A. armata, the polysaccharides derived from sulfated galactans have shown strong antiviral effects against human immunodeficiency virus (HIV), inhibiting its reproduction [62]. A study confirmed the inhibition of herpes simplex virus type 1 by different extracts of numerous red algae, including A. armata. Although the authors did not identify the compounds involved in the activity, the good results of the water extract were attributed to water-soluble polysaccharides [63]. Mannitol has been also identified in the ethanolic extract of A. armata, in a concentration of 34.70 mg/100 g of dry macroalgae [64].

In the case of C. fragile, several bioactivities have been attributed to its sulfated polysaccharides (SPs). The administration of this type of compounds reduced the oxidative damage associated with diabetes mellitus and obesity in several animal models without any cytotoxic effect [65,66]. Recently, a study stated that SPs from C. fragile scavenge effectively freed radicals in vitro and suppressed the oxidative damage caused by H₂O₂ in Vero cell cultures and in zebrafish [67]. It has also been reported that SPs from C. fragile increased the coagulation time of human blood in a dose-dependent manner according to the methods activated partial thromboplastin time (APTT) [68,69], thrombin time (TT), and prothrombin time (PT) [69]. SPs from C. fragile inhibited HeLa cells proliferation [70] by stimulating tumor necrosis factor (TNF)-related apoptosis-inducing ligand, a promising anticancer target [71].

Finally, these compounds also show immune-stimulating properties in both in vitro and in vivo models. Sulfated galactan obtained from C. fragile stimulated murine macrophages RAW264.7 cell line, increasing the levels of nitric oxide and both pro-inflammatory and anti-inflammatory cytokines, which are fundamental for the host immune response [81,82,83]. In head kidney cells, SPs had a stimulatory effect on immune genes, including interleukin (IL)-1β, IL-8, TNF-α, interferon (IFN)-γ, and lysozyme [84]. Immuno-stimulant properties have been also observed in human peripheral blood dendritic cells and T cells, which were activated by SPs. This suggests that these compounds could be candidates for products aimed to enhance human immune system [85].

S. muticum is a source of several valuable polysaccharides, such as fucoidans, alginate, guluronic and mannuronic acids, laminarin, and their derivatives [86]. Alginate obtained from S. muticum has been demonstrated to possess anticancer properties, stimulating cell death in A549 cells (epithelial lung adenocarcinoma), PSN1 cells (pancreatic adenocarcinoma), HCT- 116 cells (colon carcinoma), and T98G cells (glioblastoma) [87].

Finally, G. vermiculophylla and G. turuturu are being used in the phycocolloid industry for obtaining agar and carrageenan, respectively, turning them into valuable matrixes [88,89]. Recently, polysaccharide extracts from G. turuturu have shown antimicrobial properties against Escherichia coli and Staphylococcus aureus [90].

3.2. Lipids

Starting with A. armata, it has been reported that these macroalgae contain some sterols such as cholesta-5,25-diene-3,24-diol, (3β,24S)-form [91], palmitic and stearic fatty acids, and cholestanol [64]. Recently, different crude extracts and fractions of this species were demonstrated to present antibacterial and antifouling properties. In the crude extract and most active fractions, several compounds were identified, including hexadecanoic, dodecanoic, octadecanoic, and tetradecanoic acids, which may be involved in this activity [92,93].

Regarding C. fragile, clerosterol (a derivative of cholesterol) was found in several extracts. This compound shows antioxidant properties, since it attenuated UVB-induced oxidative damage in human immortalized keratinocyte HaCaT cells and BALB/c mice models, reducing lipid and protein oxidation [94]. In addition, clerosterol stimulated apoptosis in A2058 human melanoma cells [95] and modulated several apoptotic factors in human leukemia cells [96]. Recently, a study observed that C. fragile displayed neuroprotective effects on neuroblastoma cell line SH-SY5Y. In the most bioactive fractions, several lipid compounds, among others, were identified. Although more research is needed, the authors considered that lipids are involved in the neuroprotective effect [97].

G. vermiculophylla contains high quantity of cholesterol (473.2 mg/kg dry weight), cholesterol derivatives, long-chain aliphatic alcohols, and monoglycerides, including 1-tetradecanol, 1-hexadecanol, 1-octadecanol, 1-eicosanol, and 1-docosanol [77]. Other lipids of great interest for nutraceutical and biotechnological industries include phospholipids, glycolipids, and eicosapentaenoic acid, present in high levels in this alga [79]. For example, three sphingolipids (gracilarioside, and gracilamides A and B) isolated from G. vermiculophylla (accepted name of G. asiatica) showed moderate cytotoxic effects against human A375-S2 melanoma cell line [98].

3.3. Proteins

To our knowledge, only G. vermiculophylla presents bioactive compounds of protein nature. This alga can absorb UV-A and UV-B radiations and decrease free radicals-induced effects, resulting from its high content in mycosporine-like amino acids [99].

3.4. Pigments

Siphonaxanthin from C. fragile has shown anticancer properties, stimulating the apoptosis of A549 lung cancer cells and modulating apoptotic factors in human leukemia cells [95,96]. Moreover, the anti-angiogenic effect of siphonaxanthin has been described in human umbilical vein endothelial cells as well as in a rat aortic ring angiogenic model [100], which suggests that this biomolecule could be an alternative to prevent pro-angiogenic diseases such as cancer. In addition, this alga also contains β-carotene [76].

In recent years, fucoxanthin has received a great deal of interest from the scientific community and industry due to the many beneficial health properties attributed to it, including anti-inflammatory [101]. Fucoxanthin extracted from S. muticum inhibited the lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages and inhibited the expression of pro-inflammatory cytokines [102,103].

At industrial scale, G. turuturu is also used to produce R-phycoerythrin, a pink-purple pigment soluble in water present in large quantities, which presents diverse biological properties and potential industrial applications [89,104].

3.5. Vitamins

Different vitamins have been identified in the selected macroalgae, except in A. armata. In C. fragile, high levels of tocopherols have been reported (1617.6 µg/g lipid), including α, β, γ, and δ tocopherol and γ-tocotrienol [76]. G. vermiculophylla showed a considerable α-tocopherol content (28.4 μg/g of extract) [105]. Regarding G. turuturu, a chemical analysis revealed the presence of α-tocopherol and phytonadione (vitamin K1) [80]. Finally, S. muticum contains high amounts of α- and γ- tocopherol, 218 and 20.8 μg/g of extract, respectively [105].

3.6. Phenolic Compounds

Phenolic content has been evaluated in several species, although not all the studies have identified the target compounds. In the case of A. armata, phenolic content was determined by the Folin–Ciocalteu spectrophotometry method, which showed that it represented 1.13 ± 0.05% of dry weight [106]. Different extracts of C. fragile also contain phenolic compounds, mainly flavonoids and, to a lesser extent, tannins. These compounds showed a correlation with the antioxidant activity of the macroalgae [75]. The previous study of Farvin and Jacobsen (2013) identified several phenolic acids in both G. vermiculophylla aqueous extracts (gallic, protocatechuic, hydroxybenzoic, vanillic, syringic, and salicylic acids) and ethanolic extracts (gallic, protocatechuic, and gentisic acids). In correspondence with its content in phenolic compounds, a high antioxidant capacity has been demonstrated for these macroalgae according to the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and the ferric antioxidant power (FRAP) methods. In addition, G. vermiculophylla extracts inhibited lipid peroxidation [105]. Finally, some authors have reported the presence of phenolic compounds in S. muticum, including (ordered from highest to lowest concentration): hydroxybenzoic and gallic acids, p-hydroxybenzaldehyde, vanillic acid, 3,4-dihydroxybenzaldehyde and protocatechuic, ferulic, p-coumaric, caffeic, syringic, and chlorogenic acids [107]. Several bioactivities of S. muticum, such as antioxidant, antimicrobial, anticancer, or anti-inflammatory, have been attributed to the presence of phenolic compounds with high antioxidant capacity, particularly to phlorotannins (e.g., phloroglucinol, diphlorethol, bifuhalol), which are exclusively found in marine seaweed [78,108,109,110,111].

3.7. Other Minor Compounds

The invasive species A. armata presents high levels of halogenated secondary metabolites with recognized antibiotic activity [112]. They act as chemical defense against grazers and epibiota [113] and may be suitable for a wide range of applications [114,115]. For instance, the major metabolites bromoform and dibromoacetic acid, along with dibromochloromethane, bromochloroacetic acid, and dibromoacrylic acid, have shown high antifouling potential [72,73,74]. They can decrease the density of six bacteria strains on the algae surface: two marine (Vibrio harveyii and V. alginolyticus) and four biomedical strains (Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermis, and Escherichia coli) [116]. Recently, several brominated compounds, such as tribromomethanol, were found in the crude extract and fractions of A. armata, which showed antimicrobial antifouling potential [92,93].

A serine protease extracted from C. fragile was demonstrated to exert in vitro and in vivo anticoagulant and fibrinogenolytic activity [117]. Finally, it was found that G. turuturu contains squalene, which was reported to exert several beneficial activities [80].