Seaweeds are a rich, sustainable, and underexplored source of bioactive compounds with potent anti-inflammatory activity. Many lines of evidence indicate that various health problems may arise from chronic, dysregulated inflammatory responses, including multiple sclerosis, cancer, rheumatoid arthritis, atherosclerosis, cardiovascular disease, obesity, dermatitis, migraine, irritable bowel disease, insulin resistance, diabetes, and others [8,9,10]. Clinical and epidemiological studies have reported that elevated levels of IL-6, CRP, IL-1β are predictive of the development of type 2 diabetes and cardiovascular events [11,12,13,14]. The global burden of chronic, non-communicable diseases (NCDs), including type 2 diabetes, hypertension, obesity, some types of cancer, and CVD put enormous pressure on public health services around the world. The WHO predicts that over 70% of all deaths globally will be related to NCDs by 2025, and an estimated 41 million people will die from NCDs, including cardiovascular disease ((CVDs), (48%)), cancers (21%), chronic respiratory disease (12%) and diabetes (3%) [17]. The evidence indicates that targeting inflammatory pathways could provide a new opportunity to treat and/or prevent chronic metabolic disorders and warrants further investigations in order to develop novel and effective anti-inflammatory agents.

The application of drugs targeting inflammatory pathways appears to be a promising strategy in type 2 diabetes and CVD treatment [18,19]. However, long-duration pharmacological anti-inflammatory treatment may not be an ideal therapy in terms of adverse effects on the host defense system and long-term health outcomes [20,21,22]. Alternatively, several nutrients and bioactive compounds present in the diet have shown significant anti-inflammatory activity and may offer a safer option than pharmaceutical treatment, especially for long-term use. [23,24]. One of the most extensively studied nutrients, in relation to their immunomodulating properties, are dietary fatty acids. Long chain polyunsaturated n-3 fatty acids (LC-PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) exhibit anti-inflammatory activities [25], while some saturated fatty acids activate Toll-like receptor 4 (TLR4) and trigger inflammatory response [26,27]. EPA and DHA bind to G protein-coupled receptor (GPR120) [28] to inhibit NF-κB activation and up-regulate peroxisome proliferator activated receptor (PPAR)-γ, resulting in reduced secretion of pro-inflammatory cytokines [29]. Furthermore, marine-derived n-3 LC-PUFAs supplementation reduces blood concentrations of CRP, IL-6, and TNF-α [30].

Taking into account anti-inflammatory effects, n-3 LC-PUFAs may offer an important therapeutic option in inflammatory diseases. EPA and DHA can be derived from alpha-linolenic acid (ALA) through multiple enzymatic elongation and desaturation reactions catalysed by delta-5 and delta-6 desaturases. However, the conversion rate of ALA to DHA in humans is very low and depends on a number of external and internal factors [31,32]. Therefore, in humans DHA should be obtained from the diet by eating fish and/or other types of seafood, and plasma concentration of DHA is lower in vegetarians and vegans than in omnivores [33].

The global supply of n-3 LC-PUFAs from all known traditional sources, including capture fisheries and aquaculture, is insufficient to meet human nutritional requirements [34]. Thus, alternative new food sources of EPA and DHA are needed, and seaweeds may present an innovative source of these anti-inflammatory fatty acids [35,36,37]. Seaweeds have been used as food and in traditional medicine since ancient times in Asian countries [38] and in the last decade interest in the cultivation and use of seaweeds for human nutrition and health has grown globally [39,40,41]. Seaweeds are characterized by high nutritional quality [40,42] and are a good source of many bioactive compounds [43] with antibacterial, antiviral, antifungal, anti-oxidant, antitumor and anti-inflammatory activities [44,45]. They are also a well-known reservoir of n-3 LC-PUFAs, including EPA and DHA [39,40,46]. n-3 LC-PUFA are considered one of the most important anti-inflammatory components present in diets [126]. Thus, the inclusion of seaweed and seaweed lipids in a diet can provide preventive measures against several chronic inflammatory disorders. However, further investigations on the absorption and bioavailability of seaweed derived components are needed. In addition, any negative impact of the consumption of seaweed should be considered, especially excessive intake of iodine and heavy metals (mainly, arsenic), so there is a need to control the overall nutritional quality of seaweed and seaweed derived products [46].

 

Seaweeds are marine photosynthetic macroalgae that grow in various types of water and can be found in any climatic zone. They can be attached to rocks, pebbles, and other substrata or freely floating primitive plants that lack true root, stem, and leaves [46]. Seaweeds are classified into three groups based on their pigment composition: Ochrophyta (class Phaeophyceae, brown algae), Rhodophyta (red algae) and Chlorophyta (green algae) [47], with more than 10,000 different seaweed species identified worldwide [48]. The colour of brown algae varies from brown to yellow depending on the content of fucoxanthin that masks chlorophyll a and b, and other xanthophylls. Red algae colour varies from red to reddish-brown and purple due to the dominance of phycobiliproteins, especially phycoerythrin (red) and phycocyanin (blue-green), and in the case of green algae, their green colour is due to the presence of chlorophyll a and b [49,50]. Red seaweeds are the largest group of algae with 6100 known species and are efficient in photosynthesizing in deeper waters. On the other hand, green seaweeds (2200 known species) are common in areas where light is abundant, and the main genera includes, Ulva, Codium, Chaetomorpha, and Cladophora. There are around 1800 species of brown seaweeds, with two main orders Fucales and Laminariales, and less than 1% are found in freshwater [39,51].

Seaweeds have been harvested and used as food since ancient times in Asian countries, such as Korea, China, and especially Japan [38]. There are over 600 recognized edible seaweed species [52] and around 200 are consumed worldwide, with brown seaweeds being the most common edible seaweed (66.5%), followed by red (33%) and green (5%) [48,53]. The most popular seaweed species are nori (Porphyra/Pyropia sp.), wakame (Undaria sp.), kombu (Saccharina/Laminaria sp.), and dulse (Palmaria palmata) [40,54,55]. It is estimated that approximately one-fifth of meals consumed in Japan contain seaweed [40]. In Western countries, traditionally, seaweed intake has been limited to coastal communities, but in recent years interest in the cultivation and use of seaweeds, especially as nutraceuticals and functional food, in the West has grown [39,40,41]. In fact, the application of seaweeds to develop new food products increased by 147% between 2011 and 2015 in the European market [39,56]. Edible seaweeds are commercially available in a variety of food products, including both whole seaweed (fresh and dry) or seaweeds added as a functional ingredient to bread, confectionery, condiments, drinks, noodles and pasta, salads, snacks, soup, supplements, sushi, dairy, fish and meat products [39,42].

Seaweeds are characterized by high nutritional quality and are a good dietary source of fat- and water-soluble vitamins and essential minerals (calcium, iron, iodine, magnesium, phosphorous, potassium, zinc, copper, manganese, selenium and fluoride), with some seaweeds containing 10–100 more minerals and vitamins than terrestrial plants or animal food products [40,42,57,58]. 

They are also a good source of proteins (5–47% of dry seaweed mass, with the highest content in red seaweeds and the lowest in brown), essential amino acids and fibre (36–60% of dry seaweed mass). Lipid content of seaweeds is low, but rich in EPA and DHA [39,40,46]. This nutritional characteristic makes seaweed a healthy, nutrient-dense, and low energy food and an attractive ingredient for functional food use. In addition, seaweeds are a good source of several non-nutrient bioactive compounds such as polyphenols, sterols, flavonoids, tannins, pigments, polysaccharides, and terpenes [59]. It has been reported that these biologically active components may help to treat and/or prevent public health problems, due to their antibacterial, antiviral, antifungal, antioxidant, anti-inflammatory and antitumor activities [59,60,61]. Indeed, studies have shown that regular consumption of seaweeds was inversely associated with ischemic heart disease, mortality from stroke, and several cancers [62,63,64]. Historically, seaweeds have been used in traditional medicine, especially in East Asian countries [65], with 171 species of medicinal algae documented [58]. Some of the species of Sargassum have been successfully used to treat the symptoms of inflammation associated disorders such as the painful scrotum, edema, liver organ disease and chronic bronchitis [66,67]. According to the Korean Medical Textbook, seaweeds have been used to treat edema and painful scrotum [66].