Macroalgae, or seaweeds, provide us with several services; they have long since been used as a nutritional food resource and in traditional medicine [1], but only in the last decades, with advanced technologies, has it been possible to characterize and apply the biological properties of macroalgal compounds for biotechnological purposes. Seaweeds are a source of peculiar compounds with interesting properties that can be useful for pharmaceutical and industrial applications. Due to their non-toxic, edible, cheap and easy culturing properties, macroalgae are optimal candidates for replacing synthetic compounds with those of natural origin.

The trend of eating seaweed-based food has increased as scientific reports have confirmed the antioxidant, antimicrobial and antiviral effects of seaweed metabolites. The potentiality of seaweed can vary depending on the type of algae, harvesting period and environmental conditions; thus, every species has peculiar compounds that can act in different ways, exhibiting diverse properties.

The most important polysaccharides found in brown seaweeds are fucoidan and alginate, along with carrageenan and agar from red seaweeds and ulvan in green seaweeds [2]. Some sulphate polysaccharides have an excellent hydrocolloidal property, by creating viscous liquid. Indeed, agar and carrageenan are widely involved in the commercial food process industry due to their ability to act as stabilizers, emulsifiers and thickening agents. They are already used in gel-based food products such as desserts, jams, jellies and bakery products [3]. Seaweeds are a great source of protein, minerals, vitamins, dietary fibre, antioxidants and essential fatty acids possessing low caloric value ^[4][5][4,5]; indeed, they have been easily incorporated in the development and formulation of nutraceutical food products. In addition, studies have proved that the inclusion of seaweeds in daily alimentation is associated with low incidence of numerous diseases and provides benefits to digestive health and chronic diseases such as diabetes, cancer and cardiovascular diseases ^[6][7][8][6,7,8], as well as bacterial and viral infections ^[9][10][9,10].

2. Socio-Ecological Relevance of Seaweeds and Classification

Marine algae or seaweeds are multicellular photosynthetic primary producers widely distributed in the aquatic food chain. They are considered a fundamental component of the ecosystem as they are responsible for providing oxygen, food resources and shelter substrates for various organisms. Moreover, they provide in lowering the ocean acidity, being a possible solution to global warming ^{[11][12][13][14]}[11,12,13,14]. In Asian regions as China, Japan or Korea algae have been consumed as a whole food or ingredient since ancient times for their nutritional benefits [15]. From a nutritional point of view, they are characterized by a high content of carbohydrates (<60%) and proteins (17–44%), a low percentage of lipids (<4.5%) and high presence of other micronutrients, such as vitamins, pigments and minerals. Several seaweeds are potential candidates for biotechnological applications due to their characteristics. Their adaptation to extreme conditions increases their mechanisms of defence, thus, compounds responsible for the maintenance of seaweeds in harsh conditions might add value to the development of pharmaceutical bioproducts in order to fight diseases [16].

3. Seaweeds in Pharmaceutical Studies and Applications

Although the number of reports about new marine-derived compounds has increased, only a few have been reported a pharmacokinetic pathway. For example, Pozharitskaya et al. ^[17][132] reported the pharmacokinetics of fucoidan from Fucus vesiculosus after oral administration to rats. Other examples are given by Arunkumar et al. ^[18][133], who reported on the pharmacokinetic profiling of in vitro seaweed sulphated polysaccharides against Salmonella typhi. Shannon et al., ^[19][134] have shown seaweed’s bioactive compounds after oral administration acts as prebiotics and positively modulates the gut microbiota. Ventura et al. ^[20][135] reported on pharmacokinetic studies that evidence safety after Fucus vesiculosus polysaccharides oral absorption. Topical applications have several advantages compared to the pathway of oral administration: the pharmacokinetics are based on skin absorption; this avoids extensive first-pass metabolism and provides direct access and localization at the site of action. Topical applications are usually well-tolerated and can be an alternative for patients who cannot use other administration routes ^[21][22][136,137].

3.1. Phylum Ochrophyta, Class Phaeophyceae

Phaeophyceae are predominantly brown in colour due to their content of carotenoid fucoxanthins. These algae are recognized as an important source of bioactive compounds and other elements beneficial for human health. Fucoxanthin is an orange-coloured xanthophyll pigment ^[23][24][202,203] found in high content in Phaeophyceae, Haptophyta, Bacillariophyceae, Chrysophyceae and, to a lesser extent, in Rhodophyta, Raphidophyceae and Dinophyta. Those pigments not only give the algae their peculiar colour, but they also exhibit several biological activities such as anti-inflammatory ^[25][26][204,205], anti-obesity ^[27][28][206,207], antiangiogenic ^[29][208] and anticancer properties which can be exploited for pharmaceutical purposes. In vivo and in vitro assays showed inhibition of tumour growth in lung cancer due to fucoxanthin isolated from Laminaria japonica ^[30][140], while fucoxanthin isolated from the marine alga Ishige okamurae inhibited B16-F10 melanoma cells implanted in albino mice ^[31][168]. 

3.2. Phylum Rhodophyta

Red algae favour intertidal and subtidal zones of rocky coasts, and many of them are located deeper than brown and green algae, in cold and temperate areas ^[32][217]. In the last decade many in vitro and in vivo experiments have confirmed the pharmaceutical potential of red algae extracts ^[33][34][35][218,219,220]. Phycoerythrins of red algae possess interesting biological activities; Sekar and Chandramohan ^[36][221] describe the antitumoural effect of those pigments in mouse tumour cells and human liver carcinoma cells. Other effects reported include antioxidant ^[37][38][33,222] and antidiabetic ^[38][222], making phycoerythrins a good alternative in marine pharmaceutical ^[39][32]. Red seaweeds are the sole source of certain valuable polysaccharides, namely agar and carrageenan. Their interesting biological properties may be applied in pharmaceutical and medical applications. Carrageenans differ from structure and type, and each show different biological effects ^[40][223]. The antiviral activity of carrageenan from Gigartina skottsbergii against intraperitoneal murine HSV-1 and HSV-2 infection has been proved ^[41][121].

3.3. Phylum Chlorophyta

Chlorophyta possess high quantity of organic compounds that are interesting for pharmaceutical applications. For example, Ripol et al. ^[42][196] detected anti-inflammatory activities for five species of green seaweeds, such as Chaetomorpha linum, Rhizoclonium riparium, Ulva intestinalis, Ulva lactuca and Ulva prolifera. All species present inhibition to cyclooxygenase-2 (COX-2), the enzyme responsible for inflammation. Although, the screen of the compounds in the extract has not been performed, future research should focus on the extraction of the bioactive compounds from green macroalgae ^[42][196]. 

4. Use of Seaweeds in Traditional and Modern Pharmacology

The use of seaweeds for alimentary and medicinal purposes has been common since ancient times, especially in traditional medicine in Asian countries ^[43][44][246,247] even before the mechanisms of action of their compounds were acknowledged. For example, the crude extract of the Chinese brown seaweed Sargassum naozhouense has been used to treat fever, infections, laryngitis and other ailments by the local population ^[45][248], while species of Kappaphycus and Eucheuma genera are used in Vietnamese medicine to reduce the occurrence of tumors, ulcers and headaches. Sargassum is used for treating iodine deficiency disorders such as goitre ^[46][249]. Valuable information regarding the use of Sargassum sp. was found in ancient transcript dated between the years 25–1061 AD. Most of the transcripts have been lost, although the information of the properties of Sargassum sp. have been re-examined and collected in Chinese medical books called “Compendium of Materia Medica”, written by Shizhen Li in 1578. The most ancient information about Sargassum regards the ability of this algae to treat thyroid related diseases such as goitre, but the Compendium also affirm that Sargassum sp. can soften hard lumps, dispel nodes, eliminate phlegm and induce urination in humans ^[47][250]. Recent research on those seaweeds suggested that Sargassum sp. may play a role as an immunomodulator, as their bioactive metabolites may inhibit thyroid growth induced by excessive iodine intake and improve immune function, which may be useful in treating Hashimoto’s thyroiditis ^[48][253]. Sargassum thunbergii and Sargassum horneri have been widely used as popular medicines and food ingredients in the southeast region of China, as well as for treating scrofula, goitre, sore throat, cough and phlegm stasis, angina pectoris, dropsy, dysuria and furuncle, giving the idea to be involved in the modern Chinese medical practice ^[48][253].