**1. Introduction**

Algae are part of a heterogeneous group of photosynthetic organisms. The division includes multicellular organisms, macroalgae or seaweed (reaching sizes of up to 60 m in length), and unicellular organisms, also known as microalgae (measuring from 1 mm to several cm). One way to classify macroalgae is on the basis of their pigmentation: (i) brown seaweed (*Phaeophyceae)*, (ii) red seaweed (*Rhodophyceae*), and (iii) green seaweed *(Chlorophyceae*) [1].

Algae are distributed in diverse and extreme environments. They are valuable due to their high content in compounds with different biological activities, including both complex organic compounds and primary and secondary metabolites. Worth mentioning, among them are phytopigments (xanthophylls and carotenoids), polyunsaturated fatty acids (PUFAs) comprising docosahexaenoic acid (DHA), phenolic compounds, tannins, peptides, lipids, enzymes, vitamins, carbohydrates, terpenoids, and others. Thus, algae are a viable and economical biomass source of valuable compounds with potential applications in the nutraceutical, pharmaceutical, chemical, food, and cosmetic industries due to their biologically active and regenerative properties [2–6].

In recent years, macroalgae have gained more and more interest owed to their various health promoting properties that can decrease the risks of many chronic diseases and even help to extend the lifespan [7,8]. Macroalgae can also be used for wastewater treatment or as a natural fertilizer in agriculture, therefore improving the quality of the products and minimizing the need for chemical fertilizers [9–11]. The potential of macroalgae as a source of renewable energy is also of considerable interest. These aquatic organisms have the ability to mitigate carbon dioxide emissions and nowadays are being used as feedstock to produce "clean" or so-called "third generation biofuels" [12].

The most important applications of algae are synthetized in Figure 1.

**Figure 1.** The main applications of macroalgae.

This review focuses on the recent progress in exploitation of different macroalgae species as a source of bioactive compounds, mainly emphasizing the latter published data (between 2010 and 2020) regarding the health benefits, their bioactivities, and potential applications.

#### **2. Algae Chemical Composition**

The use of different marine macroalgae (seaweed) as sources of bioactive compounds had the advantage to exploit an under-utilized renewable natural resource. It was demonstrated that this biomass produced a broad spectrum of nutrient and bioactive secondary metabolites. The chemical composition of macroalgae varies considerably due to both environmental conditions (light intensity, growth habitat, seawater salinity, temperature) and genetic differences among species [2,13].

Macroalgae have a protein content that can range from 7 to 31% of dry weight and a lipid content ranging from 2 to 13% of dry weight [14]. A considerable amount of carbohydrate can also be found in macroalgae (up to 32–60% of dry weight).

Regarding the macroalgae content in micronutrients, they are a good source of vitamins, especially of the B-group representatives (i.e., B1, B12), as well as the lipophilic vitamins A and E (tocopherol) [13,15–17]. The richness in vitamin B12 propels the macroalgae-based products as dietary supplements for a vegan lifestyle, considered to be at risk for vitamin B12 deficiency [18]. Within the mineral composition, the most significant microelements present in the seaweeds are usually potassium, sodium, magnesium, and calcium, accounting for more than 97% of the total mineral content. Other microelements such as copper, iron, manganese, and zinc are found in small amounts (ranging from 0.001 to 0.094% of seaweeds' dry weight) [19].

#### *2.1. Protein and Amino Acid Composition*

Proteins are a major class of compounds, essential for human nutrition. For food products, the amount of protein is considered a quality parameter, but of equal importance for human health is the protein quality (e.g., protein composition in amino acids, the ratio of essential amino acids, their digestibility, and bioavailability). It is well known that seaweeds can be used as a nutrient source, especially in developing countries. In this sense, macroalgae is considered a sustainable nutrient alternative source, mainly due to high-value proteins.

Nine of the 21 amino acids are considered essential for humans, namely: histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. Proteins of animal source have a chemical score of 1.0, meaning that animal proteins contain all the essential amino acids in a minimum proportion necessary for the human body. Instead, the chemical score for cereal proteins normally ranges from 0.4 to 0.6, while the one for algae proteins ranges from 0.75 to 1.0 indicating that the protein quality of algae is superior to most terrestrial plants [14]. Therefore, macroalgae are able to cover the human requirements for essential amino acids [13].

The protein content of marine algae di ffers according to species. Although the protein level is generally low in brown seaweeds (3–15% on dry weight basis (DW)), and moderate in green seaweeds (9–26% DW), in red seaweeds the content can reach 47% DW [20]. One gram of algae meal from algae with the highest protein levels (e.g., *Enteromorpha intestinalis*, *Palmaria palmata*, and *Vertebrata lanosa)* contains equal to or higher amounts of all of the essential amino acids compared to rice, corn, and wheat. In addition, the lysine content was reported to be three to nine times higher. The approximate amount of free amino acids can range from 2 to 14.5%, the lowest amount being reported in the green algae and highest in the red varieties [13]. If we consider nonessential amino acids, the green seaweed proteins contain high levels of glutamic and aspartic acids (that can have a concentration up to 26 and 32% of the total amino acids), but also alanine and glycine [20].

The seaweed varieties that have a high protein level can be used as ingredients in the manufacturing process of di fferent foods. *Porphyra* species are known to be used in the famous sushi preparations. The same seaweeds are also processed into roasted products (such as yaki-nori) or they can be boiled in soy sauce (tsukudani-nori) [6]. For instance, species such as *Ulva pertusa*, *Enteromorpha* sp., and *Monostroma* sp. (protein levels of 26, 19, and 20% dw, respectively) are mixed together to create a food product called "aonori" (or green laver), a protein rich product very appreciated in Japan. In Europe and Canada, *Palmaria palmata* is often used as a food ingredient. Due to its high protein content (up to 35% dw), this specie of algae can be processed into dry flakes and used to obtain di fferent functional products [21,22].

#### *2.2. Lipid and Fatty Acid Composition*

The lipid content is relatively low in macroalgae species, with values less than 5% w/dw. Variations in the quantity and in fatty acids profile can be attributed to both environmental (light intensity, seawater salinity, temperature) and genetic di fferences among species. In general, it has been observed that brown species have a higher lipid content compared to green varieties [23,24].

However, nearly half of lipids are polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and arachidonic acid (AA). Red and brown algae are rich in EPA and AA, while green seaweeds such as *Ulva pertusa* predominantly contain hexadecatetraenoic, oleic, and palmitic acids, and also significant levels of PUFAs, such as linoleic acid (18:2n-6) and α-linolenic acid (18:3n-3) [23,25]. Moreover, the ratio between ω-6 and ω-3 and the ratio between PUFAs and SFAs (saturated fatty acids) found in red and brown algae are more favorable for human health than those found in green algae [26].

Besides the fatty acids, the lipidic fraction of macroalgae contains glycolipids and phospholipids. Glycolipids are carbohydrates (mono- or oligosaccharide) that are linked to a lipid (through a glycosidic bound), being essential components of the cellular membrane. Several studies were conducted on di fferent glycolipids from seaweed (e.g., monoglycosyl diacylglycerol subfraction from *Fucus distichus;* monogalactosyl diacylglycerols from *Sargassum horneri;* sulfoglycolipids from *Porphyra crispata)*, showing their anti-inflammatory and antiproliferative e ffects, respectively [27–29]. Regarding lipid extraction, Ramola et al. [30] and Margareta et al. [31] found that the most e fficient solvent was a mixture of chloroform: methanol (2:1) with an e fficiency of 14% compared to hexane (2:1) with 12.5% e fficiency.
