A review on phytoconstituents of marine brown algae

From the last few years, the development and discovery of bioactive compounds and their potential properties from marine algae have been enhanced significantly. The coastal area is a huge storehouse for propitious algae. It has been the genuine reality that the consequence of marine algae as a source of different compounds is increasing. Numerous advanced research devices are available for the discovery of synthetic compounds but still many researchers are working on natural bioactive compounds to discover their biological properties, which are useful to society. Marine algae are taking the preponderance of consideration from investigators owing to its phenomenon of biological activity like anti-cancer, anti-viral, cholesterol-reducing, and many more. A variety of compounds are collected from algae with specific purposes as they remain in an extremely ambitious and hard state; this condition is responsible for the synthesis of very particularly effective bioactive compounds. The present article is concentrating on the brown algae of the Gujarat coast, phlorotannins, polyphenol, phytosterol from brown algae, and their various applications. The main importance has been given to the secondary metabolites and various applications of marine brown algae. From this review, it can be concluded that the prominent bioactive compounds from brown algae can cure many serious diseases. Besides, the potential biological activities of a special bioactive compound may represent the interest in the industry of pharmaceuticals, cosmeceutical, and functional foods.

These active metabolites are also known as biogenic compounds, such as halogenated compounds, alcohols, aldehydes, and terpenoid, are produced by different species of marine micro and macro algae and have antibacterial, anti-algal, and anti-fungal properties that are effective in preventing biofouling and have other uses in therapeutics [1]. Sterols are the main nutritional component of seaweeds. Different species have different types of sterols, as green algae contain ucocholesterol, cholesterol, and ß-sitosterol while brown algae contain fucosterol, cholesterol, and brassicasterol. Red algae have desmosterol, cholesterol, sitosterol, fucosterol, and chalinasterol [7,8]. These properties make seaweeds more potential as a functional dietary supplement or for compound extraction. Seaweed extracts are rich in natural plant growth hormone and beneficial trace mineral. In algae extract, natural growth hormones like auxin, cytokines, and gibberellins are present in large quantities [9].
Brown algae were a huge and diverse class (Pheophyceae) of golden-brown algae varying from small filamentous form to large/giant complex seaweed. The brown algae contain the fucoxanthin pigment and different pheophycean tannins that are responsible for the characteristic greenish-brown color like the name indicated. Brown algae also provide a number of active components including unique secondary metabolites such as phlorotannin and many of them have specific biological activities that offer opportunities for their economical use [10].
The major orders found worldwide are fucales, dictyotales, and laminariales, these three orders are extensively used for bioactive compounds. More than 1140 secondary metabolites have been reported in phaeophyceae [11]. The different species of dictyotales group produce a wide range of bioactive secondary metabolites with broad defensive action against herbivores in the marine environment [12]. Among the three marine algae group, brown algae have an immense source of polysaccharide namely alginate and fucoidans, which reveals good biological activities such as anti-cancer, anti-viral, antiinflammatory, and anti-proliferative [1]. Bioactive compound fucosterol abundantly reported in brown algae and has so many biological activities such as anti-cancer [13], cholesterol-reducing [14], and anti-diabetic properties [15]. Brown algae are mainly used in different conditions such as hypothyroidism, cough, asthma, fatigue, stomach pain, hemorrhoids, and headache. It has been also used to promote weight loss and help in skincare [16]. There are various benefits of brown seaweed including reduced inflammation, blood thinning and cancer prevention [17]. Brown algae consist of a significant level of phenolic compound, a complex type of polysaccharide, extremely high biological activity, and more effective antioxidant compared to green and red algae [18]. Therefore, the objective of the present review is to focus on the distribution of brown algae along the coast of Gujarat, its bioactive compounds, and the bioactivity of isolated compound from it.

Distribution of brown algae
Eighty percent of the world's plant diversity has been recorded only in the aquatic environment, including over 150,000 species of algae found in intertidal zones and tropical waters of the seas, and it is the main source of natural products [19]. There are approximately 8000 species of marine macroalgae discovered on the world's coastlines, and they can exist up to 270 m deep. A total of 25 species of green algae, 90 species of brown algae, and 350 species of red algae are found in the global coastline area which is commercially important because of their biochemical content [20]. About 1500 species of brown algae has been identified worldwide [21]. Brown algae are observed in about 6, 91, 713 places around the world (Fig. 1).
There are about 265 genera and 2040 species belong to class Phaeophyta (Fig. 2), in which 95% of those species are most widespread in cold to temperate waters. All data shown in the figure was accessed via GBIF on 21 October 2020. The GBIF (Global Biodiversity Information Facility) is an international network and research foundation supported by government authorities around the world and providing data on all types of life around the world.
The main sources of algae are found in the northwest, west-central and southwest Atlantic, and in the centraleast and southwest Pacific. India, with its long coastline, has vast marine resources along many open coasts and estuarine areas. Marine benthic algae of India were first published in 1970 with 20 species [22]. Based on the reports published in different journals, [23][24][25] prepared the updated checklist of algae. The checklist prepared in 2001 comprises a total of 280 species from the Gujarat coast [24]. Seaweeds on the Indian coast consist of 814 species belonging to 217 genera. Out of these species, 216 species of Chlorophyta, 191 species of Phaeophyta, 217 species of Rhodophyta, and 3 species of Xanthophyta were recorded on Indian coasts among these 202 species were found only in Gujarat [26]. The coastline of Gujarat is made up of Deccan traps and tertiary stones and in places; there are fossilized forms of milliolite with limestone [27]. A list of brown algae recorded in the coastal area of Gujarat has been described in Table 1.

Prominent secondary metabolites in brown algae
Marine algae represent a good source of secondary metabolites/specialized metabolites. These specialized metabolites play important role in defense against pathogens. Phlorotannin, phytosterol, and polyphenol are prominent secondary metabolites groups that are found in brown algae. The variety of compounds within a particular group plays a vital role in many biological activities. Some prominent secondary metabolites from brown algae are as follows.

Phlorotannins
Polyphenols of marine algae are known as phlorotannins, which are observed in seaweeds and synthesized by the acetate-malonate pathway also known as polyketide pathway produced by the polymerization of phloroglucinol. Phlorotannins are extremely hydrophilic components with a wide range of molecular sizes between 126 kDa and 650 kDa [28]. Among the green, brown, and red seaweeds, phlorotannins are normally isolated from the brown seaweed. This phytochemical has been isolated through chromatographic methods [29,30]. In addition, for characterizing the structure of compounds, nuclear magnetic resonance spectroscopy has been used [31,32]. It has been recorded that members of laminariaceae are a rich source of phlorotannins compare to other seaweeds [33]. Phlorotannins have different biological activities such as anti-diabetic, antioxidant, anti-proliferative, anti-HIV, and skin protection, radioprotective, and anti-allergic activities [34]. Cystophora congesta have phlorotanin likes phloroglucinol triacetate, diphlorethol pentacetate, and triphlorethol-A-heptacetate [35]. The extract of Cystoseria showed good antioxidant and cytotoxic results, which can suggest that it can be effectively used in the synthesis of the cytotoxic  drug [36] and have bieckol, fucophloroethol, 7phloroeckol, and phlorofucofuroeckol compound [37]. Different species of Ecklonia revealed antioxidant, anticancer, and anti-diabetic properties due to the presence of different phlorotannin compounds like fucodiphlorethol G, phloroglucinol, eckol, dieckol, and phlorofucofuroeckol A [38][39][40][41][42][43]. Edible brown algae Eisenia arborea was used in folk medicine and showed anti-allergic properties owing to the phlorofucofuroeckol B compound [44]. Himanthalia elongate showed high anti-microbial and antioxidant activity, due to the presence of phloroglucinol [45]. Ishige okamurae showed the presence of diphloretohydroxycarmalol phlorotannin [46]. A list of phlorotannins in brown seaweeds has been recorded in Table 2.

Phytosterol
Sterols are found in animals as well as plants. The sterols found in plants are known as phytosterol [47].
Phytosterol is a bioactive compound in marine algae, terrestrial, and marine plants. There are about 200 types of phytosterol have been found [48]. Stigmasterol and sitosterol are two common examples of phytosterols [49]. Mostly, brown seaweeds contain fucosterol and fucosterol derivatives [7]. These bioactive compounds are important because of the many beneficial health effects associated with them. The determination of phytosterols is generally performed by mass spectrometry or flame ionization detection [50]. The phytochemical compound fucosterol was first isolated by RP-HPLC method in Cystoseria foeniculacea and Dictyota ciliolate, and the fraction of compound also analyzed by NMR technique [51]. Bioactive compound fucosterol was responsible for anti-proliferative and cytotoxic properties in Padina sanctae-Crucis and Dictyota ciliolate [52]. HPLC analysis of brown algae Himanthalia elongate, Undaria pinnatifid, and Laminaria ochroleuca have showed the presence of steroid compounds like fucosterol and cholesterol [7]. By performing GC-MS analysis in brown algae, Hormophysa triquetra and Padina pavonica showed the presence of important phytosterols like fucosterol, stigmasterol, campesterol, and β-sitosterol [53]. Padina gymnospora and Sargassum angustifolium has great antioxidant activity and testified that they have a good source of fucosterol, brassicasterol, cholesterol, and stigmasterol by GC-MS analysis [54]. Sargassum asperifolium have important phytosterol compound like fucosterol, stigmasterol, saringosterone, and saringosterol [55], which gave good biological activities to it. The amount of phytol and fucosterol was quantified in edible brown algae Sargassum fusiforme [56]. A list of phytosterols reported in brown seaweeds has been recorded in Table 3.

Polyphenols
Polyphenols are a group of prominent secondary metabolites, which support the plant in structural development and protect the algae from biotic and abiotic stress condition [57]. Brown algal species have unique secondary metabolites namely as polyphenols and phlorotannin compound are a class of these polyphonic compound [58], this type of compound were formed under harsh condition and able to absorb UV-radiation and repair wound [59]. Polyphenols have great biological activities; these characters make brown algae used as major ingredients for cosmeceutical and nutraceutical products [60]. Polyphenols have shown therapeutic properties such as anti-oxidative, anti-bacterial, anti-cancer, anti-allergic, anti-diabetes, anti-aging, anti-inflammatory, and anti-HIV activities [61,62].
Different brown algae showed immense in vitro antioxidant activity and quantified the polyphenolic compound using the HPLC method [63]. It has been reported that Fucus species have gallic acid, protocatechuic acid, genistic, vanillic acid, and caffeic acid; Sargassum multicum have a good source of gallic acid, protocatechuic acid, genistic, vanillic acid, caffeic acid, and syringic; Saccharina latissima have gallic acid, protocatechuic acid, genistic, vanillic acid, and Laminaria digitata showed the presence of gallic acid, protocatechuic acid, genistic, vanillic acid, and caffeic acid. These phenolic compounds are responsible for the great antioxidant activity of algae [63]. Brown algae Himanthalia elongate confirmed the natural antioxidant compound like gallic acid, chlorogenic acid, caffeic acid, ferulic acid, and quercetin [45]. It has been testified that Padina boergesenii have important phenolic compound such as gallic acid, caffeic acid, rutin, quercetin, and ferulic acid which can be used as cancer chemopreventive agent [64]. HPLC profiling of Padina pavonica confirmed the presence of polyphenol compounds like kaempferol, tannic acid, caffeic acid, quercetin, and epigallocatechin, and FTIR analysis confirmed the presence of various groups like phenol, alkanes, alcohol, and aromatic compounds [65]. Different species of Sargassum have shown the major polyphenolic compound like gallic acid and Phydroxybenzoic acid, the presence of this compound was confirmed by RP-HPLC method [66]. A list of polyphenols reported in brown seaweeds has been recorded in Table 4.

Biological importance of the isolated compound from the brown algae
Diterpen bifurcadiol 76 has been isolated from Bifurcaria bifurcate; this diterpens shows cytotoxic activity against human tumor cell line; metaterpenoids from Sargassum tortile showed cytotoxic activity [67].  10.
It has been recorded that, compared to green and red algae, brown algae have shown higher anti-microbial activity against different aquaculture pathogens [75]. A variety of bioactive compounds are synthesized by marine algae, subjected to tolerate environmental changes such as radiation, stress, water pressure, and high temperature [76]. Brown algae contained polysaccharides such as laminarin, alginic acid fucoidan, and sargassan [76], and this type of algal polysaccharides showed anti-cancer activity [77]. Phlorotanins are a type of tannin, belongs to the group of polyphenolic compounds, which has usually found in brown algae. These polyphenols inhibit colon cancer cells [78]. Terpenes are also recorded in brown algae. In terpenes, halogenated monoterpenes are important in different biological activities. Isolated halogenated monoterpenes showed important anti-proliferative activity [79] (Fig. 3).
It has been testified that brown seaweeds are a good source of sterols like fucosterol and desmosterol, and it has been recorded that this type of sterols decreases the level of cholesterol, free triglyceride in the liver [80]. Phloroglucinol is polyphenolic compound, which showed different biological activity such as anti-oxidant, anti-diabetic, anti-inflammatory, anti-allergic, and anti-HIV [81][82][83][84][85][86]. The phlorotannins (phloroglucinol, eckol and diekol) from brown algae E. cava have been used in cosmeceuticals products [80]. Edible brown algae Eisenia arborea have phlorofucofuroeckol-B, shown strong antioxidant activity, it suggests a potential use in antiallergic drug preparations [44]. The sulfated polysaccharides from Padina tetrastomatica have been used in  cancer treatment because it showed strong antioxidant and anti-mitotic activity [87]. A brown algae Sargassum vestitum has active compound fucoxanthin which showed antioxidant activity, it suggests possible use in the food and pharmaceutical field [5]. Fucoid component from Dictyota merttensi, Spatoglossum schroederi, and Fucus vesiculosus which contain the inflammation response for their anti-inflammation activity [88]. Lamina japonica has strong antioxidant activity due to the fucoid component in it which inhibits the increased formation of lipid peroxide in serum and liver [89] (Fig. 4). Brown algae Chnoospora minima displayed significant antiproliferative activity on cancer cell lines due to the bioactive fraction [90].

Conclusion
The review work on the phytoconstituents of brown algae makes it clear that this large group of marine algae is not only used to obtain food, fodder but is an enormous source of several secondary metabolites. This review paper holds studies of the bioactive compound of brown algae, which has many more functional properties compared to red and green algae because phaeophyta group are main representative of polysaccharide and fucoidans which are responsible for prominent biological activity. It has been noted that the types and proportions of phytoconstituents vary from species to species and depend on environmental factors. The multiple mechanisms of action promote the formation of complex bioactive compounds from brown algae, which directly enhanced their biological activity, and such activities promote many drug industries for drug production. Thus, systematic work on this group of marine algae will be helpful in the formulation of new drugs that can be used for curing several fatal diseases of a human being.