Review of Sargassum thunbergii (Fucales, Phaeophyta): phycology, chemistry, bioactivity, and application
Article information
Abstract
Sargassum thunbergii is a large brown seaweed endemic to the Northwest of Pacific Ocean, widely distributed in the warm temperate coastal waters of South Korea, China, and Japan. It is abundant in resources and has a long history of application, widely used in food, medicine, and feed. In recent years, it has also been used to restore marine ecology. To date, only one review has been published on Sargassum thunbergii aquaculture. Therefore, by investigating the international definitive data repository (ScienceDirect, PubMed, Web of Science, ACS Publications, Springer, etc.) and collecting 92 kinds of literature closely related to phycology, chemistry, biological activity, and applications, herewith a comprehensive and systematic summary and exposition, enveloping the classification and distribution, botanical characteristics, and physiological and biochemical differences of Sargassum thunbergii; involving 7 chemical classifications of 117 derivatives substances embracing 12 new and 6 first-isolated excluding polysaccharides; mainly including 11 types of pharmacology in vivo and in vitro; evaluating the potential applications related on medicine, healthcare, aquaculture, and marine restoration. This review is expected to provide forward-looking scientific perspectives and act as a valuable reference for future studies, development, and utilization of Sargassum thunbergii.
INTRODUCTION
With more than 70% of the Earth’s surface covered by oceans, marine ecosystems are incredibly rich in biodiversity, accounting for approximately half of the global biodiversity. Such vast and complex habitats make marine organisms an important source of natural products and constitute a treasure trove of compounds with structural diversity and biological functionality (Yende et al. 2014). Among numerous marine organisms, seaweed has attracted much attention due to its complex chemical composition and significant biological activity. Seaweed belongs to a class of heterogeneous photosynthetic organisms with a long evolutionary history, among which macroalgae are particularly important and are the main contributors to marine natural products (Pereira 2018). As an important primary producer of aquatic ecosystems, seaweed contributes about 50% of the planet’s primary productivity and is widely used in food, feed, and various industrial and biomedical fields (Carina et al. 2021). Therefore, seaweed is not only of great ecological importance but also an important resource for the development of new natural products.
The genus Sargassum is a brown algae with about 400 species, widely distributed in the oceanic basins of the Atlantic, Pacific, and Indian Oceans, mainly thriving in low-latitude regions, forming thick benthic macroalgal communities (Mattio and Payri 2011, Kim et al. 2017, Song et al. 2025). Sargassum thunbergii Kuntze (ST) is a macroalgae exclusive to the Northwest Pacific Ocean, which is the dominant species and is widely distributed in littoral areas of Asia, especially in Korea, China, and Japan (Song et al. 2021). It is ecologically and economically significant, contributing crucially to the formation and upkeep of coastal marine ecosystems (Phillips 1995, Li et al. 2017b). At the same time, ST, a traditional marine plant with the same origin as medicine and food, plays an active role in human life and health (Shalaby 2011, Chen et al. 2016). Therefore, the chemical taxonomy of ST holds significant importance for the identification, potential development, and ensuring consistent product quality control.
However, ST competes with the brown algae Sargassum fusiforme (Tot named in Korea, and Hiziki in Japanese) (Wang et al. 2025). In South Korea and other East Asian countries, Tot is more widely accepted as food, and overfishing has led to a year-on-year decline in Tot production (Javed et al. 2025). In addition, since the taste and flavor of ST are not suitable for direct consumption, it is crucial to study its industrial development as a biomaterial or functional food ingredient or raw material. Therefore, summarizing and exploring the chemical classification and activity research of ST lays the foundation for further development and quality control of ST.
METHODS AND SUMMARY
The following databases were searched from their receptions until December 2025: PubMed, ACS publications, Springer, Wiley, ScienceDirect, Web of Science, and Royal Society of Chemistry. The keywords used for the literature search included: Sargassum thunbergii, combined with Phytochemistry, Pharmacology, Bioactivity, and Application. The initial time node is the first release node until December 2024, and the update time node is until December 2025. The use of standardized authentication and deposition methods is indispensable. The selected studies are required to adhere to a general protocol that includes controlling constituent substances, reporting authenticated reference standards and chromatographic profiles, and providing detailed analytical procedures along with validation data. Papers in the English language was included for this review (Fig. 1).
Screening flow chart of literature searching for Sargassum thunbergii.
In recent years, scholars have confirmed its application in food and medicine through its chemical composition and pharmacological effects. A review article on ST has been identified, focusing on ST genetic diversity and cultivation (Liu et al. 2021). Although some comprehensive reports on the genus Sargassum included ST, the assessment of both is not systematic and exhaustive enough. So far, various secondary metabolites, such as polysaccharides, fatty acids, volatile organic compounds (VOCs), alkaloids, phenolics, isoprenoids, steroids, etc., have been isolated or detected from ST. This review summarizes the botanical features, chemical composition, bioactivities, and practical applications of ST based on literature published up to 2025. The aim is to systematically and extensively evaluate the potential of ST in different areas based on available information. It is anticipated that this review will serve as a useful reference for future fundamental and applied development research on this species (Fig. 2).
Graphical summary of the content.
PHYCOLOGY
Sargassum thunbergii is a typical kind of macroalga that originally belongs to the phylum Brown Algae, the class Rounds, the order Fucussophyta, the family Sargassum, and the genus Sargassum in the phylogenetic taxonomy (Yoshida 1983). However, modern classification systems indicate that ST belongs to Ochrophyta, Phaeophyceae, Fucales, Sargassaceae (Silberfeld et al. 2010). Basionym is Fucus thunbergii Mertens ex Roth. Homomorphic synonyms are Cystoseira thunbergii (Mertens ex Roth) C. Agardh, Myagropsis thunbergii (Mertens ex Roth) Kützing, and Turbinaria thunbergii (Mertens ex Roth) Yendo. And heterotypic synonyms are Fucus swartzii C. Agardh, Rhodomela swartzii (C. Agardh) C. Agardh, Myagropsis swartzii (C. Agardh) Kützing, and Sargassum swartzanum Yendo (Liu et al. 2021). It was first characterized by Otto Kuntze, a German botanist, in 1880 (Kuntze 1881). ST exhibits unique characteristics in their branching system, with each major branch developing into an individual-like spindle. This appearance gives ST its vernacular name, which is called Djichungi in Korea, meaning “earthworm,” Shuweizao in China (meaning “mouse tail alga”), and Umitoranoo in Japan (Table 1) (Koh et al. 1993, Zhuang et al. 1995).
Sargassum thunbergii synonym list
ST is extensively distributed in the warm temperate nearshore waters of South Korea, China, and Japan, often forming a wide algae bed in the intertidal zone, playing an important role in maintaining the structure stability and functional integrity of local coastal ecosystems (Li et al. 2017a). This species usually grows luxuriantly and can form seaweed forests with other Sargassum spp. and kelp that serve as spawning, nursery, and feeding grounds for marine animals (Liu et al. 2016a). ST grows year-round, thriving best from March to July, on in the intertidal zone of the rocks, or in puddles or marshes of the high and middle tidal zones, and even in low-tide areas exposed to prolonged sunlight (Li et al. 2012). ST has been widely studied for its unique ecological and economic value. However, due to the lack of available genomic information, further research in this area is constrained to a certain extent (Liu et al. 2014). Performed genomic analysis on ST and compared with the published cytoplasmic genomes of five brown seaweed (Ectocarpus silulosus [Ectocarpales], Fucus vesiculosus [Fucales], Saccharina japonica [Laminariales], Undaria pinnatifida [Laminariales], and Costaria costata [Laminariales]), the gene content and sequence of ST were identical to those of Fucus vesiculosus (Fucus) (Yang et al. 2016).
ST is highly differentiated and has perennial stipe, stigma, branchlet, blade, and pneumatocyst (Koh et al. 1993). The thallus of ST is dark brown in color. The holdfast is flattened and discoid or conical, firmly attaching the alga to the substrate. A short, cylindrical primary stipe (approximately 6 mm in length) arises from the holdfast, bearing conspicuous scale-like leaf scars on its surface. There are multiple primary branches at the top of the main trunk, and their appearance often varies due to changes in branch length and internode distance. The juvenile branches are densely enveloped by imbricate leaves arranged in a tight spiral pattern during the initial growth stage. Secondary branches subsequently develop from the leaf axils. Occasionally, the secondary branches remain very short and unelongated. The surface of the branches is marked with distinct longitudinal grooves. The young leaves are densely clustered along the main stipe, resembling the cones of pine trees. As they mature blade, they take on a filamentous-lanceolate, oblique-cuneate, or spatulate, with margins entire or coarsely serrate, measuring 5–10 mm long and roughly 2 mm wide. The thallus length and biomass of ST were significantly correlated with variations in air temperature, seawater temperature, photoperiod, and tidal zonation (Liu et al. 2016b). Abundant pneumatocyst are present on the thallus of ST, typically narrow fusiform or obovoid, with an acute apex and pedicels of unequal length. The receptacle is oblong-elliptic or cylindrical, blunt apex, and grows in solitary or clustered between leaf axils, with the plant being dioecious. The male receptacle is relatively elongate and smooth, while the female receptacle is thicker, shorter, and exhibit a rough texture on the surface (Yoshida 1983, Han and Li 2005, Wang and Liu 2007, Heo et al. 2024).
Dioecious plants have a significant impact on maintaining the stability of terrestrial ecosystems and conserving biodiversity (Xia et al. 2024). The morphological and structural differences between ST males and females lead to physiological and biochemical differences. The prevailing bacterial phyla and genera of ST males and females are the same, while there are notable variation observed in the relative abundance of epiphytic bacteria classified at the genus level. Moreover, male and female ST have their indicator variety and unique bacteria (Wang et al. 2022, Zhao et al. 2024). ST is the most dominant dioecious seaweed in the intertidal zone, which is more susceptible to the effects of ultraviolet B (UV-B) radiation, causing light stress and exacerbating thermal stress and dry stress conditions (Chu et al. 2012). After exposure to UV-B irradiation, male ST exhibited a more stable response to UV-B interference than females by relying on metabolic processes such as photoprotection mechanisms, intracellular osmotic pressure regulation, and accumulation of stress-resistant metabolites (Sun et al. 2022). However, female macroalgae exhibit higher activity in the carbon metabolism pathway, where fixed carbon is more inclined to be allocated to lipid synthesis and the tricarboxylic acid (TCA) cycle. The excessive representation of the TCA cycle and lipid anabolism allows the female to store a large amount of energy, thus guaranteeing the completion of their reproductive stage. On the contrary, male algae were more active in nitrogen metabolism pathways such as nitrogen fixation and glutamate metabolism, which was conducive to the growth and development of algae and enhanced their resistance to the external environment (Qiu et al. 2023).
CHEMISTRY
In the past 30 years, many studies have focused on marine ecosystems, which have approximately 250,000 to 500,000 species of organisms, revealing that marine organisms also produce a variety of structurally diverse compounds (Kang et al. 2023). The intertidal zone is one of the most environmentally stressed areas on the planet, and ST is one of the most predominant dioecious seaweeds here, a transition zone between the marine and terrestrial environments (Sun et al. 2022). This also leads to ST showing strong resistance to environmental pressures such as high temperature, strong light, and dryness, contributing to its strong survival ability (Kim et al. 2024). This phenomenon indicates that ST secondary metabolites have high diversity and structural complexity. Therefore, ST has gradually become a research hotspot, and more and more scholars have conducted systematic and in-depth research on it, successfully isolating and identifying a large number of compounds with potential biological activity. To date, the chemical structures of 120 compounds, excluding polysaccharides, have been isolated or detected from ST. Based on the classification method of marine natural chemicals, the chemical composition of ST mainly includes polysaccharides, fatty acids, VOCs, alkaloids, phenolics, isoprenoids, steroids, and others. The separation or detection methods of the compound are shown in Tables 2–7.
The extraction, isolation, purification, and structure identification of polysaccharides from Sargassum thunbergii
Volatile organic compounds in Sargassum thunbergii (Wang et al. 2021)
The extraction, isolation, purification, and structure identification of alkaloids in Sargassum thunbergii
The extraction, isolation, purification, and structure identification of phenolic compounds in Sargassum thunbergii
The extraction, isolation, purification, and structure identification of isoprenoids and steroids in Sargassum thunbergii
The extraction, isolation, purification, and structure identification of other compounds in Sargassum thunbergii
Polysaccharides
Polysaccharides are high molecular weight (MW) polymeric carbohydrates composed of multiple monosaccharide units connected by glycosidic bonds. They are widely present in various organisms such as plants, microorganisms, algae, and animals (Xie et al. 2016, Yu et al. 2018). Together with polynucleotides, proteins, and lipids, polysaccharides constitute the four most important biological macromolecules in the life sciences, participating in many biological processes such as intercellular interaction, embryogenesis, microbial infection, and humoral and cellular immunity (Liu et al. 2015). Seaweed contains a large number of polysaccharides, especially in the cell wall structure. The total level of polysaccharides in seaweed varies from species to species, accounting for approximately 4% to 76% of its dry weight. Among them, brown seaweed is rich in polysaccharides, with polysaccharide content usually exceeding 50% of dry weight. The main types of polysaccharides in brown algae include fucoidan, seaweed polysaccharides, and alginates, which have important structural and physiological functions. The common methods of extraction mainly include hot water extraction and enzymatic extraction techniques, which are suitable for polysaccharide separation and functional activity maintenance under different application requirements (Senthilkumar et al. 2013, Zhou et al. 2024). Due to the unique structural characteristics of polysaccharides, such as MW, monosaccharide composition, charge properties, and glycosidic bonds, they exhibit various bioactivities, including antioxidant, anti-inflammatory, anti-viral, anti-aging, and anti-tumor effects (Nagahawatta et al. 2023). Seaweed polysaccharides have been proven to have many benefits for human health and are currently widely used in different industrial fields such as food, medicine, and cosmetics (Tanna and Mishra 2019).
Thirty-one polysaccharide fractions were isolated and purified from ST by fractional extraction, iron exchange chromatography, and gel filtration. Based on in vivo activity screening, the two components, GIV-A ([α]25D-127°, molecular weight, 19,000) and GIV-B ([α]25D-110°, molecular weight, 13,500), were found to be fucoidan or L-fucoidan based on chemical and spectroscopic analysis. Each fucose residue contained about 30% sulfate group, about 10% of uronic acid and less than 2% protein (Zhuang et al. 1995).
Under the optimized conditions of 120 mL g−1-solid-liquid ratio, a 210-min extraction time, and 97°C, the polysaccharide yield obtained from ST was 7.53%. The main component, STP-II, was obtained by fractional purification of the resulting polysaccharides by DEAE-Sepharose CL-6B column chromatography. The structure of STP-II was characterized by high-performance liquid chromatography (HPLC) and gas chromatography (GC), and the results showed that its content accounted for 63.75% of the total polysaccharides, and the relative MW was about 550 kDa, mainly composed of xylose, fucose, glucose, glucuronic acid, and galactose (Yuan et al. 2015). Then, the structure of STP-II was deconstructed by Fourier transform infrared spectroscopy (FT-IR), periodic acid oxidation (HIO4)-Smith degradation, acid partial hydrolysis, methylation analysis, and nuclear magnetic resonance spectroscopy (NMR). The results showed that the backbone was mainly composed of (1 → 3)-linked-fucose, (1 → 3)-linked-xylose and (1 → 3)-linked-galactose, with a branched content of about 17.5%. Branched chains and terminal residues mainly included (1 → 2)-linked-glucuronic acid, (1 → 4)-linked-glucose, (1 →)-linked-xylose, and (1 →)-linked-4-O-acetyl-glucose. Together, these structural features reveal the repeating unit composition of STP-II (Luo et al. 2016). A novel polysaccharide, mainly formed of entangled chain and linear (STPSP-1), was confirmed by comprehensive analysis techniques including GC, FT-IR, HIO4-smith degradation, partial acid hydrolysis, methylation coupled with GC-mass spectrometry (MS), NMR, and transmission electron microscopy. STPSP-1 was composed of fucoidan and galactose, with a molar ratio of 1.2 : 1, and a relative MW of around 373 kDa. Its main structural components → 4)-α-D-Galp-(1 → and → 3)-β-L-Fucp-(1 → (Luo et al. 2019).
The water-soluble polysaccharide (STPC2) obtained by precipitation of boiling water extract with CaCl2 and purification by DEAE-cellulose-Sephacryl S-300 column chromatography was composed of fucose, xylose, galactose, and glucuronic acid (8.1 : 3.8 : 2.1 : 1.0), with a MW of 57 kDa (Ou et al. 2017). The optimization process, utilizing a microwave-assisted extraction method with an extraction time of 23 min, microwave power of 547 W, and an extraction temperature of 80°C, coupled with a material-to-water ratio of 1 : 27 g mL−1, resulted in ST polysaccharide (STP-1) containing 2.84 ± 0.09% carbohydrate, 32.7% protein, and 15.2% sulfate content. The main MW is 190.4 kDa, consisting of arabinose, galactose, glucose, xylose, mannose, galacturonic acid, and glucuronic acid, with molar percentages of 1.94, 30.7, 4.54, 23.2, 17.6, 8.11, and 13.9%, respectively (Ren et al. 2017). The chemical composition analysis of the sulfated heteropolysaccharides separated by anion-exchange chromatography showed that the fucose content was 19.70%, the sulfate group was 14.81%, the total sugar content was 87.98%, the uric acid was 18.06%, and the relative MW was about 135 kDa. The molar ratio of monosaccharide composition was mannose : rhamnose : glucuronic acid : glucose : galactose : xylose : fucose = 0.59 : 0.08 : 0.31 : 0.04 : 0.47 : 0.08 : 1.00. After desulfurization, the desulfurized polysaccharide contains methyl glycosides of galactooligosaccharides, mono-sulfate, and galactic-disulfate oligosaccharides (Jin et al. 2018). The chemical constitution of sulfated galactose named ST-2-L was determined by DEAE Bio Gelagarose FF gel (6 cm × 40 cm), which included fucose (31.36%), sulfate (23.01%), total sugar (75.48%), uric acid (2.43%), and the molar ratio of a single one was 0.04 : 0.03 : 0.05 : 0.04 : 0.41 : 0.02 : 1.00 (mannose : rhamnose : glucuronic acid : glucose : galactose : xylose : fucose) (Jin et al. 2019).
Fatty acids
Affected by the unique marine habitat, marine organisms can synthesize many types of lipid molecules. Among them, fatty acids, as the basic structural units of triglycerides and wax esters, constitute the main components of marine-derived fats and oils (Bergé and Barnathan 2005). Although the lipid content of seaweed is significantly lower than that of marine fish, it is still considered a functional lipid source with potential for exploitation due to its widespread distribution and abundant biomass in coastal waters (Miyashita et al. 2013). Polyunsaturated fatty acids can exert antioxidant effects through mechanisms such as scavenging free radicals, and may have a protective effect on chronic diseases to a certain extent by reducing or cleaning levels of reactive oxygen species (ROS) (Richard et al. 2008). The lipid content of seaweed varies due to environmental factors such as species characteristics, geographical distribution, seasonal changes, temperature, salinity, and light intensity (Sánchez-Machado et al. 2004a, 2004b). Brown algae contain a lot of essential fatty acids and polyunsaturated fatty acids (Ganesan et al. 2019). A total of 27 fatty acids were detected by GC-MS, including octanoic acid (1), decanoic acid (2), undecanoic acid (3), dodecanoic acid (4), tridecanoic acid (5), myristic acid (6), myristoleic acid (7), pentadecanoic acid (8), palmitic acid (9), palmitoleic acid (10), heptadecanoic acid (11), cis-10-heptadecanoic acid (12), stearic acid (13), elaidic acid (14), linoleic acid (15), γ-linolenic acid (16), linolenic acid (17), arachidic acid (18), cis-11-eicosenoic acid (19), cis-11,14-eicosadienoic acid (20), eicosatrienoic acid (21), arachidonic acid (22), cis-5,8,11,14,17-eicosapentaenoic acid (23), behenic acid (24), erucic acid (25), tetracosanoic acid (26), cis-4,7,10,13,16,19-docosahexaenoic acid (27) (Kim et al. 2010b). The main fatty acid is arachidonic acid > arachidic acid > palmitic acid > elaidic acid > linoleic acid > stearic acid > cis-5,8,11,14,17-eicosanoic acid (Kim et al. 2010a).
Volatile organic compounds
VOCs mean organic molecules with low MW, varying hydrophilicity from low to moderate, and high vapor pressure that can penetrate cell membranes and be released into the atmosphere (Fink 2007, Gressler et al. 2009). The synthesis of VOCs involves the removal of the hydrophilic moiety as well as oxidation/hydroxylation, reduction, methylation, and acylation reactions (Pichersky et al. 2006). Seaweed is also an important source of naturally occurring VOCs. After harvesting, endogenous enzyme activity, chemical reactions, and microbial interactions in seaweed collectively promote the formation of a series of characteristic volatile compounds, including hydrocarbons, ketones, aldehydes, alcohols, organic acids, and halogenated compounds, which give seaweed and its derived foods unique and rich aroma and flavor characteristics (Ito and Hori 1989, Li et al. 2023).
The VOCs of seven species of seaweeds in the Yellow Sea of China were studied by multi-fiber headspace solid-phase microextraction combined with GC-MS, and the detection results showed that ST contained 19 VOCs, namely: one aromatic hydrocarbon compound (isocumene 28, 1.14%), one furan derivative (2-propyl-furan 29, 1.37%), three alkenes (ectocarpene 30, 3.40%; 1-pentadecene 31, 4.31%, 5.46%; 8-heptadecene 32, 5.97%, 14.82%), three alkanes (heptadecane 33, 1.63%, 1.59%; pentadecane 34, 9.24%, 13.87%; cyclopentadecane 35, 2.94%, 1.51%); three alcohols (2,7-dimethyl-1-octanol 36, 0.94%; (E)-2-undecen-1-ol 37, 1.48%; 2-propyl-1-pentanol (38, 0.82%); two isoprenes (β-cyclocitral 39, 1.05%; (E)-β-ionone 40, 1.22%, 0.93%); five aldehydes (tridecanal 41, 11.46%, 11.02%; tetradecanal 42, 0.62%, 0.48%; (Z)-11-pentadecenal 43, 5.49%, 5.85%; pentadecanal 44, 6.86%, 11.33%; (Z,Z,Z)-7,10,13-hexadecatrienal 45, 0.91%) (Wang et al. 2021).
Alkaloids
Alkaloids are an important class of structurally diverse compounds, referring to a class of nitrogen-containing organic compounds derived from the biological world (Sireesha et al. 2019). Due to the lone pair electrons on nitrogen in alkaloids usually accept protons (H-acceptors), while the hydrogen in primary and secondary amines acts as proton donors (H-donors) required for hydrogen bonding, which allows them to exhibit bioactivity with medicinal value by forming hydrogen bonds or charge interactions with the active sites of biomolecules such as proteins or enzymes (Kittakoop et al. 2014). There are two main types of alkaloids: heterocyclic alkaloids containing nitrogen in heterocycles (also known as typical alkaloids), and non-heterocyclic alkaloids containing nitrogen in their side chains (also known as atypical alkaloids or protoalkaloids) (Cushnie et al. 2014). With the continuous excavation of metabolic products of marine organisms, not only have typical alkaloids been obtained, but also halocyclic alkaloids that cannot be found in terrestrial plants have been discovered (Güven et al. 2010). Previous studies have suggested that marine alkaloids have antioxidant, anti-cancer, anti-inflammatory, and other effects (Zhang et al. 2024, Singh et al. 2025).
So far, 21 typical alkaloids have been isolated and identified from ST, most of which are indole alkaloids. Four new compounds (N-(4′-hydroxyprenyl)-cyclo(alanyltryptophyl) (46), isovariecolorin I (47), 29-hydroxyechinulin (48), and 30-hydroxyechinulin (49) are indole-diketopiperazine alkaloids, which are isolated from endophytes named Eurotium cristatum EN-220 of ST. In addition, nine known indole diketone piperazine alkaloid compounds, rubrumline M (50), rubrumazine B (51), neoechinulin B (52), neoechinulin C (53), alkaloid E-7 (54), didehydroechinulin (55), echinulin (56), dehydroechinulin (57), and variecolorin H (58), were obtained (Du et al. 2017). Indole-derived compounds indole-2-carboxaldehyde (59), indole-3-carboxaldehyde (60), indole-4-carboxaldehyde (61), indole-5-carboxaldehyde (62), indole-6-carboxaldehyde (63), and indole-7-carboxaldehyde (64) were isolated from the 80% methanol (MeOH) extract of ST (Kang et al. 2017). Notably, variecolorin was present in compounds (47) and (48) during the separation. In addition, halosmysin A (65) and halosmysins B (66) are new 14-membered macrodiolide isolated from the fungus Halosphaeriaceae sp., isolated from ST, with an unprecedented structure (Yamada et al. 2020, 2022).
Phenolics
Phenolic compounds are composed of one or more aromatic ring structures with hydroxyl functional groups, and their structures range from simple molecules to high MW molecules (Lomartire et al. 2021). There are two main biosynthetic pathways for the production of phenolic chemicals. One is the shikimate/phenylpropane pathway, which provides phenylpropanoids starting from phenylalanine produced by the shikimic acid pathway. The second method is the acetic acid-malonic acid pathway, which can produce polyketones (Vogt 2010, Cotas et al. 2020). These compounds not only play a vital role in the structure formation and growth governance of primary and secondary cell walls in plants but also form an important foundation for various physiologically active substances in plants (Wallace and Fry 1994).
Phenolic compounds are one of the most abundant and bioactive secondary metabolites synthesized by seaweed, especially brown seaweed. They are used to resist various biotic and abiotic stresses and have made significant contributions to the growth and development of seaweed (Aina et al. 2022). Seaweed phenols mainly include simple phenols, phenolic acids/aldehydes, flavonoids, tannins, polyphenols, etc., which have biological activities like antioxidant, anti-inflammatory, and anti-cancer (Jimenez-Lopez et al. 2021). Currently, 12 phenols and their derivatives have been isolated and detected from ST. Two new tetraprenyltoluquinols, thunbergols A (67) and thunbergols B (68), as well as three tetraprenyltoluquinol derivatives, namely sargahydroquinoic acid (69), sargaquinoic acid (70), sargachromenol (71), sargachromanol D (72), Sargathunbergol A (73), and sargachromanol E (74) (Seo et al. 2004, 2006, 2007, Kim et al. 2010b, 2016); two novel resorcinols, 1-(5-acetyl-2,4-dihydroxyphenyl)-3-methylbutan-1-one (75) and 1-(5-acetyl-2-hydroxy-4-methoxyphenyl)-3-methylbutan-1-one (76) (Cai et al. 2010); and known compounds diphlorethol (77) (Tsukamoto et al. 1994). The study found that ST produced a higher polyphenol content (34.99 mg) compared to plants Undaria pinnatifida Suringar (25.34 mg) and same genus seaweed Sargassum miyabei (23.26 mg). In addition, the presence of phloretin (78) was detected in ST through GC-MS (He et al. 2022). The optimized ST extract (the optimal extraction conditions: 12.0 min, 65.2°C, ethanol (EtOH) concentration 53.5%) had high antioxidant and whitening effects, and caffeic acid (79) was identified by liquid chromatography–tandem mass spectrometry (Gam et al. 2021).
Isoprenoids
Isoprenoids, also known as terpenes or terpenoids, are an important component of living organisms (Lohr et al. 2012). Isoprene is the basic structural unit of all isoprene-like compounds, with a typical five-carbon skeleton (Harder 2010). In eukaryotes, isoprene can be synthesized via the mevalonate pathway and/or the methylerythritol phosphate pathway. Almost all plant species can synthesize isoprene precursors utilizing these two metabolic pathways (Sohn et al. 2021). To date, eleven isoprenoids have been isolated and identified in ST, three of which are norisoprenoids: (+)-isololiolide (80), (−)-loliolide (81), and apo-9′-fucoxanthinone (82). Two drimane-type sesquiterpenoid compounds 6-hydroxy-4-(hydroxymethyl)-3,4a,8,8-tetramethyl-4a,5,6,7,8,8a-hexahydronaphthalen-1(4H)-one (83) and 4,6-dihydroxy-4-(hydroxymethyl)-3,4a,8,8-tetramethyl-4a,5,6,7,8,8a-hexahydronaphthalen-1(4H)-one (84) were isolated from the endophytic fungus Fusarium solani 2024f-xx in ST (Xu et al. 2025). In addition, loliolide acetate (85), grasshopper ketone (86), 3α-hydroxy-5,6-epoxy-7-megastigmen-9-one (87), deacetylate-apo-13′-fucoxanthinone (88), apo-13′-fucoxanthinone (89), (R)-(−)-3-hydroxy-β-ionone (90), and Sargassumketone (91) were also isolated. Among them, compound (86) is a new compound; compounds (82), loliolide acetate (85), 3α-hydroxy-5,6-epoxy-7-megastigmen-9-one (87), apo-13′-fucoxanthinone (89), and (R)-(−)-3-hydroxy-β-ionone (90) were isolated from ST for the first time; Although (80) had been isolated from terrestrial plants, it was the first time that it had been isolated from marine organisms (Park et al. 2004, Jiang 2012).
Steroids
Steroidal compounds (derived from the Greek word stereos, meaning “solid”) are a class of solid alcohol that are widely found in plants and animals, and their basic skeleton is composed of 17 carbon atoms, arranged in the form of cyclopentanoperhydrophenanthrene (Bhatti and Khera 2012). Natural steroids are instrumental in a variety of physiological processes, comprising immune regulation, stress response, protein catabolism, carbohydrate metabolism, blood electrolyte balance, as well as inflammation and behavior regulation (Rasheed and Qasim 2013). Marine macroalgae are a good source of steroidal compounds (Ghaliaoui et al. 2024). To date, eight steroidal compounds have been isolated from ST. Thunberol (92), a new sterol, was derived from the East China Sea. Four known analogues, 24-ethylcholesta4,24(28)-dien-3-one (93), stigmasta-5,28-dien-3b-ol (94), cholesta-5,14-dien-3β-ol (95), and cholesta-5,23-dien-3β,25-diol (96) were also isolated (He et al. 2014). In addition, fucosterol (97) was isolated from ST 95% EtOH extract (Jiang 2012). HPLC analysis showed that the content of fucosterol in Haeundae-gu extract was relatively high (~10.23 ± 0.17 mg g−1 extract) (Lee and Kang 2025). Isofucosterol (98) and saringosterol (99) were isolated from ST chloroform (CHCl3) extracts (Kim et al. 2014).
Others
In addition to the above components, ST also contains hydrocarbons, esters, glycolipids and other compounds. Two types of exo-methylenic alkapolyene compounds (6Z,9Z,12Z,15Z)-1,6,9,12,15-henicosa pentaene (HEP, 100) and (6Z,9Z,12Z,15Z,18Z)-1,6,9,12,15-henicosa hexaene (HEH, 101) were isolated from ST (Kurihara et al. 2014). The 95% EtOH extract was separated and separated from normal phase and reverse phase silica gel column chromatography (silica gel CC), Sephadex LH-20 gel column chromatography, and semi-preparative HPLC to obtain cyclic ester named 2-hexenoicacid-4,4-dihydroxy-2,3-dimethyl-γ-lactone (102), chain ester named hexadecanoic acid 2′,3′-dihydroxypropyl ester (103), amide compound named (R)-2-hydroxy-3-phenylpropanamide (104), and thymidine (105) (Jiang 2012). Chlorophyll a (106) was isolated from ST CHCl3 extract (Kim et al. 2014). Isolation of cyclic ester compounds colletodiol (107) and halosmysins C (108) from the fungus Halosphaeria sp. isolated from ST (Yamada et al. 2020, 2022). Two new polyhydroxy compounds fusasolpolyol A (109) and (4E,8E,12E)-2,3,7,11-tetrahydroxy-2,4,6,8,10,12-hexamethylt etradeca-4,8,12-trienoic acid (110) were isolated from another endophytic fungus Fusarium solani 2024f-xx isolated from ST (Xu et al. 2025). Separation of ST MeOH extract by silica gel CC and reverse phase HPLC to obtain a mixture of sulfolipids, sulfoquinovosyl diacylglycerol (111) (Tsukamoto et al. 1994). Two new monogalactosyl diacylglycerols (2S)-1-O-(5Z,8Z, 11Z,14Z,17Z-eicosapentaenoyl)-2-O-(9Z,12Z,15Z-octadecatrienoyl)-3-O-β-D-galactopyranosyl-sn-glycerol (112) and (2S)-1-O-(9Z,12Z,15Z-octadecatrienoyl)-2-O-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-3-O-β-D-galactopyranosyl-sn-glycerol (113), as well as two known glycolipids, (S)-2-(((6Z,9Z,12Z,15Z)-octadeca-6,9,12,15-tetraenoyl)oxy)-3-(((2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl) tetrahydro-2H-pyran-2-yl)oxy)propyl (5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaenoate (114) and (S)-3-(((2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl) tetrahydro-2H-pyran-2-yl)oxy)propane-1,2-diyl (9Z,9′Z,12Z,12′Z,15Z,15′Z)-bis(octadeca-9,12,15-trienoate) (115) were isolated from the moderately polarcomponents of the ST MeOH extract by reversed-phase silicon flash chromatography (Kim et al. 2007). Monogalactosyl glycerol named (2R)-1′-O-glyceryl β-D-galactopyranoside (116), galactolipid named (2S)-1,2-O-diacylglyceryl β-D-galactopyranoside (117), 96 : 4 mixture of the sodium salts of 1-O-palmitoyl-and 1-O-oleoyl-3-O-(6′-sulfo-α-D-quinovopyranosyl) glycerol (118), and sodium ((2S,3S,4S,5R,6S)-6-((R)-2,3-dihydroxypropoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl) methanesulfonate (119) were separated and identified by silica gel CC and TSK gel chromatography (Son et al. 1992). A new Arseno-sugar named 3-{[5-Deoxy-5-(trimethylarsonio) pentofuranosyl]oxy}-2-hydroxypropyl sulfate (120) was isolated from ST, in which the dimethylarsinyl group was substituted, and it had a trimethylarsonium group carried by arsenic betaine (Shibata and Morita 1988).
BIOACTIVITY
Because of ST growing in the unique environment of the intertidal zone, which enables it to have the adaptability to a variety of environmental challenges in terms of morphological structure, physiological characteristics, and molecular mechanisms. These environmental factors are prone to induce oxidative stress response in STs, making their anti-inflammatory and antioxidant properties a research hotspot. Based on its special growth environment, relevant research has delved into the biological activities of ST in various facets such as anti-inflammatory, anti-tumor, antioxidant, anti-obesity, and antibacterial (Table 8).
Study on the bioactivity of Sargassum thunbergii
Anti-inflammatory effect
Inflammation is an adaptive defense reaction of the body to noxious stimuli or pathological conditions such as infection and tissue damage (Medzhitov 2008). Chronic inflammation contributes to a significant portion of the global disease burden. It is recognized by persistent diffusion of immune cells such as monocytes, dendritic cells, and macrophages, and underlies diseases including atherosclerosis, obesity, and certain cancers (Nathan and Ding 2010). Natural products have a strong anti-inflammatory effect, with high activity and low toxicity and side effects, and show great potential in the field of anti-inflammatory properties (Azab et al. 2016). Many unique bioactive compounds have been extracted from oceanic organisms with anti-inflammatory effects, mainly by inhibiting the production of pro-inflammatory factors, negatively regulating inflammatory signaling pathways, regulating immune cell responses, and inhibiting enzymes such as lipoxygenase (LOX) or promoting the resolution of inflammation through mediators such as regressin (Gressler et al. 2009, Sugimoto et al. 2016, Serhan and Levy 2018).
Multiple studies have demonstrated that ST has anti-inflammatory activity. Researchers mainly studied the anti-inflammatory, anti-hepatitis, anti-atherosclerotic, and immune-enhancing effects of ST based on mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways, and primarily applied lipopolysaccharide (LPS)-induced RAW264.7 cells and BV-2 cells in vitro, as well as mouse and zebrafish larvae models in vivo. The pyretolytic agent, anodyne, and anti-inflammatory activities of ST’s dichloromethane (CH2Cl2), EtOH, and boiling water extracts were tested in mice. The activity of yeast-induced fever, tail-flick test, and phorbol-induced acetic acid inflammation (erythema, edema, and blood flow) was evaluated. ST EtOH extract (STE; 0.4 mg ear−1) suppressed edema by 72.1%, while the anti-edema rate of indomethacin (0.3 mg ear−1) as a standard drug was 83.7%. After oral delivery of the extract (5 g kg−1 bw), no acute toxic reactions were observed, indicating that ST had significant anti-edema activity and no obvious toxic side effects, demonstrating its potential application value in the treatment of inflammation-related symptoms (Kang et al. 2008). ST ethyl acetate (EtOAc) extract inhibited pro-inflammatory mediators production, including nitric oxide (NO) (IC50 = 20.2 μg mL−1), prostaglandin E2 (IC50 = 14.9 μg mL−1), interleukin (IL)-6, and tumor necrosis factor-alpha (TNF-α) in RAW264.7 cells induced by LPS in a dose-dependent manner, which may be due to the high content of phlorotannin in the extract (44.8%) (Yang et al. 2010). STE significantly diminished NO production in LPS-stimulated BV-2 microglia in a dose-dependent manner (p < 0.001 at 20, 40, 80, and 100 μg mL−1) with inhibition rates ranging from 13 to 65%. In addition, STE downregulated the inducible nitric oxide synthase (iNOS) expression and reduced TNF-α soluble protein by 16–47%, thereby weakening the inflammatory response initiation (Lee and Kang 2015). Use a pickle-derived bacterium (Lactobacillus sp., SH-1) fermented ST, which significantly inhibited the NO production in RAW264.7 cells stimulated by LPS at 1,000 μg mL−1 (inhibition rate of 93%) and the expression of iNOS, cyclooxygenase-2 (COX-2), TNF-α, IL-1β, and IL-6. The fermentation process mainly blocks MAPKs activation in macrophages induced by LPS, especially c-Jun N-terminal kinase (JNK) signaling levels, to enhance anti-inflammatory effects. In a comparative analysis, the 85% MeOH and n-hexane fractions significantly inhibited the production and expression of these factors in a dose-dependent manner. The fermentation process of Lactobacillus sp. SH-1 might have an advantageous effect on the biological activity and molecule content in the extract, thereby promoting the development and application of fermented algae as potential anti-inflammatory nutritional supplements (Mun et al. 2017).
At the dose of 75 and 150 μg mL−1 linear polysaccharides (STPSP-1), had a favorable inhibitory effect on the mRNA expression of IL-6, TNF-α, and COX-2 in LPS-induced RAW 264.7 cells, and the inhibition effect was 99.5, 95.5, and 93.2% at 150 μg mL−1, respectively (Luo et al. 2019). ST sulfated galactofucan inhibited inflammation through the Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88)/NF-κB signaling pathway, thereby attenuating atherosclerosis. It decreased IL-1, IL-6, and TNF-α levels in the serum of male ApoE-KO mice induced by a high-fat diet, but didn’t reduce blood lipids. It can downregulate the mRNA and protein expressions of TLR4 and MyD88, reduce phosphorylated p65 (p-p65) levels, and alleviate atherosclerosis in ApoE-KO mice. The sulfated galactofucan inhibited the pro-inflammatory cytokines production and TLR4, MyD88, and p65 mRNAs and protein expressions in RAW 264.7 cells stimulated by LPS. These studies supported that sulfated galactofucan may have anti-inflammatory effects on ApoE-KO atherosclerosis mice by inhibiting the macrophage TLR4/MyD88/NF-κB signaling pathway, and may be a potential drug for resisting atherosclerosis (Zhu et al. 2024). Fucoidan was optimized to increase NO production in both RAW 264.7 cells and zebrafish and activated the immune response by motivating NF-κB pathway-related proteins, including COX-2, iNOS, p-p65, and phosphorylated inhibitor of kappa B alpha (p-IκB-α). In vitro, it enhanced the phagocytic activity of macrophages and dose-dependently upregulated the TNF-α, IL-6, IL-1β, and IL-10 secretion, which can be used as an immune enhancer in functional foods and nutraceuticals (Yang et al. 2023). In addition, the compound indole-4-carboxaldehyde (ST-I4C) (100 μM) attenuated methylglyoxal (MGO) by activating NF-κB, induced the expression of inflammation-related genes, TNF-α, and interferon-γ, in HepG2 cells. Exposure to MGO induced translocation of NF-κB into the nucleus, while ST-I4C treatment before exposure to MGO prevented its translocation. ST-I4C decreased MGO-induced AGE formation and AGE receptor (AGE) expression. Glyoxalase-1 (Glo-1) mRNA and protein expression levels increased after ST-I4C treatment (Cha et al. 2019). Indole-6-carboxaldehyde (I6CA), also obtained from ST indole derivatives, had immunomodulatory effects, which can significantly enhance the phagocytic ability of RAW 264.7 cells, and significantly increase cytokine secretion and related gene expression. I6CA significantly stimulated the expression of TLR4 and its aptamer MyD88, and enhanced the complexation between TLR4 and MyD88, by increasing the degradation of NF-κB-α inhibitors to promote NF-κB (Park et al. 2020a).
Antioxidant effect
Oxidative stress is a state caused by the increased production of ROS or reactive nitrogen species (RNS) or the impairment of the body’s antioxidant defense system, distinguished by the failure of endogenous antioxidants to function properly to neutralize these species effectively, resulting in oxidative damage to biological targets (Sies 1985). ROS/RNS can induce cell death through nonphysiological (e.g., necrosis) or programmed regulatory mechanisms (e.g., apoptosis), typically involving receptor activation, activation of caspases, regulation of B-cell lymphoma 2 (Bcl-2) family proteins, and disruption of mitochondrial function (Ryter et al. 2007). At present, various in vitro chemical assays have been applied to evaluate the antioxidant activity of marine-derived compounds, including the oxygen radical absorbance capacity assay, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, and iron-reducing antioxidant capacity (FRAP), etc. (López-Alarcón and Denicola 2013). Seaweed contains a large amount of highly active derivative compounds, which have great potential for application in development and production due to their strong stability and increasing demand from consumers for antioxidant-rich products such as functional foods, drugs, and cosmetics (Lee et al. 2025). As a species of Sargassum, ST not only has high nutritional value, but also is one of the important sources of natural antioxidant compounds that have attracted much attention (Catarino et al. 2023).
The potential of ST to scavenge authentic peroxynitrite anion (ONOO−) and 3-morpholinoaniline (SIN-1)-derived ONOO− of different components was compared with the antioxidant order of MeOH-H2O > n-butanol > n-hexane > H2O (Seo et al. 2004). Enzymatic hydrolysis of ST was performed using carbohydrases (Celluclast, AMG, Ultraflo, Termamyl, and Viscozyme) and proteases (Flavorzyme, Alcalase, Neutrase, Kojizyme, and Protamex) to prepare water-soluble extracts and compare their antioxidant activities. The results showed that alcalase hydrolysis products exhibited the most outstanding performance in scavenging DPPH, alkyl, and hydroxyl, with IC50 values of 1.35, 3.82, and 7.15 μg mL−1, respectively. In addition, the removal rates of hydrogen peroxide by Alcalase and Ultraflo extracts reached 93 and 91%, respectively, and both exhibited good thermal stability at 100°C (Park et al. 2005). STE inhibited the ability of DPPH free radical production in a concentration-dependent manner, with the greatest effect at a concentration of 1 mg mL−1 (Lee and Kang 2015). The antioxidant activity of ST subcritical water extract was detected by in vitro antioxidant assay. 2,2’-Azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), DPPH, and FRAP were 88.62 ± 2.35 (Trolox equivalent), 45.56 ± 0.23, and 34.47 ± 0.49 mg TE g−1 in dry samples, respectively. Compared with Undaria pinnatifida and Saccharina japonica, ST hydrolysate showed the highest FRAP activity (Park et al. 2023). ST has nutritive efficacy in preventing ROS-induced tissue damage and potential natural antioxidants associated with oxidative stress due to its presence of various unsaturated fatty acids. Various cell lines (mouse macrophages RAW264.7, human leukemia cells HL60, and U937) were utilized to examine the antioxidant efficacy of ST. ST extract (>50 μg mL−1) was concentration-dependent on eliminating intracellular ROS, inhibiting protein oxidation, and reducing lipid hydroperoxides in RAW264.7. It exhibited a significant dose-dependent inhibitory effect on DNA damage induced by H2O2 in U937 cells, restoring the expression levels of superoxide dismutase (SOD-1) and glutathione reductase. Concentration-dependent reduction of myeloperoxidase activity in HL60 cells showed significant inhibitory effects (approximately 75%) at high concentrations (100 μg mL−1) (Kim et al. 2010a). ST MeOH extract provided concentration-dependent inhibition of DPPH free radical generation, with inhibition rates exceeding 87% at concentrations better than 50 μg mL−1; it also inhibited ROS generation and membrane protein oxidation in HT1080 cells in a dose-dependent manner, with inhibition rates of 97 and 41%, respectively at 100 μg mL−1; at concentrations greater than 50 μg mL−1, the fluorescence intensity of diphenyl-1-pyrenylphosphine oxide was similar to that of the blank group, indicating that the extract can inhibit cell membrane lipid peroxidation (Kim et al. 2010b).
Compounds of sargahydroquinoic acid, sangaquinoid acid, and sargachromenol show peroxynitrite scavenging activity comparable to L-ascorbic acid and penicillamine (Seo et al. 2004). Thunbergols A and thunbergols B isolated from ST MeOH extract had obvious DPPH removing activity, with EC50 of 30 and 31 μg mL−1, respectively. They also potently inhibited the production of ONOO− by morpholinosydnonimine (SIN-1) at a concentration of 98.6 and 90.6%, at a dose of 5 μg mL−1, respectively (Seo et al. 2006). Thirteen compounds isolated from the ST endophytic bacterium Eurotium cristatum EN-220 were evaluated for their antioxidant effect against DPPH and superoxide anion radicals, with dehydroechinulin exhibiting potent scavenging activity against DPPH radicals (IC50 = 6.4 μg mL−1), comparable to ascorbic acid (IC50 = 2.0 μg mL−1) (Du et al. 2017). I6CA (300 or 400 μM) blocked H2O2-induced ROS production in mouse V79-4 fibroblasts and C2C12 skeletal muscle cells, prevented DNA damage, protected mitochondrial function, inhibited mitochondrial membrane potential loss and cytochrome C release, and reduced the Bcl-2-associated X protein (Bax)/Bcl-2 expression ratio and the activity of caspase. By suppressing apoptosis in C2C12 cells, I6CA restored intracellular ATP levels and decreased acetyl-CoA carboxylase (ACC), thereby inhibiting AMP-activated protein kinase (AMPK) activation. In V79-4 cells, I6CA alleviated G2/M phase arrest, downregulated the cyclin-dependent kinase inhibitor p21WAF1/CIP1, increased cyclins A and B1 expression, and activated the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway to protect cells from hydrogen peroxide (H2O2)-induced oxidative stress and apoptosis (Kim and Choi 2020, Park et al. 2020b). ST polysaccharides, STP-1 and STP-2, had free radical eliminating ability, and the cleaning rates of DPPH free radicals were 95.23 and 90.80%, respectively, at a concentration of 0.4 mg mL−1. The neutralizing activity of hydroxyl radicals was concentration-dependent, and the free radical quenching rates of STP-1 and STP-2 were 72.4 and 68.7% at a concentration of 0.8 mg mL−1, respectively (Ren et al. 2017). ST linear polysaccharides STPSP-1 scavenged superoxide radicals (EC50 = 0.22 mg mL−1) and hydroxyl radicals (EC50 = 0.88 mg mL−1) with comparable effects to vitamin C (VC) and may have potential antioxidant effects (Luo et al. 2019). ST polysaccharide was effective in scavenging hydroxyl radicals, superoxide radicals, with higher scavenging activity against hydroxyl radicals (76.72% at 0.7 mg mL−1) and superoxide anions (95.17% at 2 mg mL−1) than VC. STP-II also exhibited antiproliferative capacity in human colon cancer Caco-2 cells (IC50 = 4.07 mg mL−1). STP-II exhibits excellent antioxidant capacity and inhibitory effects on Caco-2 cells in vitro (Yuan et al. 2015).
Anti-obesity effect
Obesity has become a rapidly growing public health issue worldwide, showing an epidemiological trend, and is closely linked with an accelerated risk of premature death (Van Gaal et al. 2006). As a chronic and recurring disease, obesity can lead to a series of serious metabolic disorders, particularly diabetes, cardiovascular disease, hypertension, and non-alcoholic fatty liver disease (Endalifer and Diress 2020). The main mechanism involves the overexpansion of white adipose tissue (WAT), where adipocytes release large amounts of free fatty acids (FFAs) through enhanced lipolysis, resulting in elevated serum fatty acid levels and further aggravating metabolic disorders (Cao 2014, Thakuri et al. 2023). Peroxisome proliferator-activated receptors (PPARs) belong to a class of ligand-dependent transcription factors in the nuclear hormone receptor superfamily, in which PPARγ is a key regulator of adipogenesis. PPARγ can be activated by various endogenous fatty acids and regulated by fatty acid synthesis factors like sterol regulatory element binding proteins 1 (SREBP1), further inducing another key adipogenic transcription factor named CCAAT/enhancer-binding protein-α (C/EBPα), thereby jointly initiating the differentiation and adipogenesis process of adipocytes (Fajas et al. 1999, Kubota et al. 1999, Rosen et al. 2002).
Seaweed consumption has shown potential therapeutic value in weight control and obesity management. In vitro and in vivo studies have provided most of the currently existing data. Up to now, various extracts or monomeric compounds from ST have been proven to have anti-obesity properties. STE had been shown to have good anti-obesity effect in vitro and in vivo. In vitro, 20 mg mL−1 significantly inhibited lipid accumulation in 3T3-L1 cells, reduced adipogenesis genes (C/epba and Pparg), and enhanced metabolic sensors, including Ampk and sirtuin 1 (Sirt1), thermogenic genes, including peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc-1α) and uncoupling protein 1 (Ucp1), and proteins such as p-AMPK/AMPK and UCP1. In vivo, 100 and 300 mg kg−1 significantly reduced body weight and fat accumulation in high-fat diet (HFD)-induced C57BL/6 mice, while reducing serum levels of insulin (0.96 ± 0.21, 1.13 ± 0.42 mg kg−1), leptin (2,859.6 ± 1.35 and 2,299.6 ± 0.3 mg kg−1), triglycerides (22.5 ± 2.54, 23.28 ± 1.87 mg kg−1), and total cholesterol (74.59 ± 5.65 and 73.76 ± 1.61 mg kg−1), which are similar to Garcinia cambogia (sample concentration: 165 mg kg−1; levels in serum: 1.76 ± 0.71 mg kg−1, 2,218 ± 0.01 mg kg−1, 21.55 ± 3.33 mg kg−1, 67.24 ± 7.3 mg kg−1) and orlistat (sample concentration: 10 mg kg−1; levels in serum: 1.05 ± 0.28 mg kg−1, 3,638 ± 0.09 mg kg−1, 25.40 ± 3.63 mg kg−1, 79.13 ± 5.55 mg kg−1). ST inhibited fat accumulation by improving glucose intolerance, downregulating PPARγ in WAT, upregulating the expression of the mesothermogenic genes UCP-1 and UCP-3 in brown adipose tissues, and increasing Bacteroides vulgatus and Faecalibacterium prausnitzii abundance in the gut microbiota (Kang et al. 2020, Kim et al. 2022). The CHCl3 fraction derived from the ST MeOH extract (IC50 = 1.98 mg mL−1) exhibited higher anti-obesity activity, and the isolated compounds—isofucosterol, chlorophyll a, and saringosterol—had 2 to 4 times lower lipase inhibitory activity than that of the CHCl3 : MeOH (100 : 1) fraction (FI, 83.78% at 1 mg mL−1), suggesting that the strong lipase inhibitory activity of F1 was not due to a single compound but rather the synergistic effect of these three compounds (Kim et al. 2014). Thunberol (IC50 = 2.24 mg mL−1) exhibited notable inhibitory activity against the protein tyrosine phosphatase 1B, a key therapeutic target for type II diabetes and obesity treatment, indicating that thunberol and its analogs may serve as promising candidates for the development of treatments targeting these metabolic conditions (He et al. 2014). Among the six indole derivatives isolated from 80% MeOH extract, both I2CA and I6CA significantly reduced lipid buildup in 3T3-L1 cells, inhibited PPARγ, CCATAT/C/EBPα, and sterol regulatory element-binding protein 1c (SREBP-1c) expression, and activated AMPK phosphorylation in a dose-dependent manner (Kang et al. 2017). Fucoidan fractions (STAF3, 50, 100, and 200 μg mL−1) purified from ST starch glucosidase-assisted hydrolysate significantly downregulated the expression of adipogenic PPARγ and fatty acid binding protein 4 proteins, as well as lipogenic SREBP-1 protein to inhibit lipid accumulation in 3T3-L1 adipocytes. In vivo, oral administration of STAF3 (250 mg kg−1) effectively reduced the body weight and fat mass of HFD-induced mice, significantly reduced serum Triglycerides (27.47 ± 2.36 nmol μL−1) and total cholesterol (65.43 ± 3.89 μg L−1), and was comparable to the positive control groups Garcinia cambogia (sample concentration: 165 mg kg−1, 23.37 ± 5.42 nmol μL−1, 69.17 ± 8.83 μg μL−1) and orlistat (sample concentration: 10 mg kg−1, 26.08 ± 3.88 nmol μL−1, 77.33 ± 5.07 μg μL−1). STAF3 significantly improved lipid accumulation in liver fat and white adipose tissue, and reduced the expression of lipid-producing PPAR-γ and SREBP-1 genes in white adipose tissue, effectively reducing adipogenesis and lipogenesis (Lee et al. 2024a).
However, the mechanisms of anti-obesity are different in different cell lines. ST low molecular weight polysaccharide (LMPST) effectively reduced lipid accumulation and intracellular accumulation of FFAs and triglycerides by palmitic acid (PA)-induced 3T3-L1 and HepG2 cells. The levels and trends of LMPST were not significantly different from those of the positive control quercetin (12.5, 25, and 50 μg mL−1). LMPST inhibited the overexpression of PPARγ and C/EBP-β in 3T3-L1 cells and restrained the blocking effect of PA on p-AMPK. However, in HepG2 cells, PA inhibited the expression of PPARγ and p-AMPK, while the expression levels increased after LMPST treatment, and the levels of carnitine palmitoyltransferase 1 and phosphorylated ACC (p-ACC) were also increased, which means that LMPST inhibited intracellular lipid accumulation by regulating the fatty acid oxidation pathway in hepatocytes (Lee et al. 2024b).
Anti-tumor effect
Cancer is a complex of related diseases in which cells continue to proliferate abnormally and spread to surrounding tissues, eventually forming tumors. The pathogenesis is multifactorial, which may be related to drug abuse, infectious pathogens, poor dietary habits, environmental carcinogens, genetic mutations, hormonal imbalances, and abnormal immune function. These factors may synergize with each other or act sequentially to promote the occurrence and development of carcinogenesis (Gutiérrez-Rodríguez et al. 2018). Many plant-derived natural products have shown powerful anti-tumor properties. Previous research has shown that ST exhibits significant anti-tumor potential, mainly manifested in anti-leukemia, anti-lung cancer, and anti-angiogenic activity.
As a preliminary screening for anti-tumor activity, the cancer cell proliferation inhibition properties of halosmysin A, halosmysins B, and halosmysins C were estimated using mouse P388 and L1210, human HL-60 leukemia cell lines. Halosmysins A exhibited good inhibitory activity against all these cells with IC50 values from 2.2 ± 3.1 to 11.7 ± 2.8 μM (Yamada et al. 2020, 2022). The structure-activity relationship of ST polysaccharides affects their anti-tumor potency against human lung cancer A549 cells. Based on the strength of anti-tumor activity, the activity of ST polysaccharides was investigated from the aspects of extraction method, growth location, molecular weight, sulfate and urea acid content, and fraction. The results showed that the high MW hot water extract from Qingdao, China had the strongest anti-tumor activity, with higher MW indicating stronger activity, and uronic acid had an impact on anti-tumor activity (Jin et al. 2017). The sulfated galactofucan in ST had a significant growth inhibitory effect on A549 lung cancer cells, with irregular cell morphology, increased cell volume, and large nuclei, exhibiting aging-like changes, which can induce cell senescence and death, increased expression of p53, p21, and p16, and reduce phosphorylated Rb (p-Rb) in the high dose (3 mg mL−1). Transferring cells into BALB/c-nu mice, sulfated galactofucan was capable of reducing the volume of tumors without affecting the body weight of the mice (Jin et al. 2019, Bao et al. 2020). In addition, water-soluble polysaccharides significantly inhibited the migration and proliferation of lung cancer cell line A549, restrained the expression of the matrix metalloproteinase (MMP)-2 gene at the transcription level and enzyme activity, and decreased the mRNA and protein vascular endothelial growth factor-A and hypoxia-inducible factor-1α expression in endothelial cells (Ou et al. 2017). ST sulfated galactoidan also had antiangiogenic activity versus human umbilical vein endothelial cells (Jin et al. 2019). In human dermal fibroblasts, ST enhanced activation of MMP-2, whereas in human fibrosarcoma cells (HT1080 cells), the presence of ST reduced MMP-9 activation (Park et al. 2011). I6CA markedly attenuated the secretion and protein expression of MMP-9 in HT1080 cells stimulated by phorbol 12-myristate 13-acetate, which had been identified as mediated by inhibition of JNK and extracellular signal-regulated kinase phosphorylation and activation, NF-κB p65 nuclear translocation, and IκBα phosphorylation and degradation (Kim et al. 2019).
Antimicrobial effect
Seaweed produces metabolites that help protect resist different environmental stressors. These compounds have antiviral, protozoan, antifungal, and antimicrobial properties (Pérez et al. 2016). The antibacterial research on ST is relatively limited, and existing studies mainly focus on the antibacterial activity of its extracts. It mainly inhibited five kinds of bacteria, namely Gram-negative bacteria Escherichia coli, Enterobacteriaceae, Vibrio parahaemolyticus, as well as Gram-positive bacteria Bacillus cereus and Staphylococcus aureus.
V. parahaemolyticus is a facultative anaerobic bacterium widely present in marine and coastal environments and is one of the important pathogens causing bacterial foodborne gastroenteritis in humans (Su and Liu 2007). ST low MW polyphenols (900 μg mL−1) suppressed the propagation of V. parahaemolyticus in the logarithmic phase, damaged the cell membrane and cell wall of the tested bacteria, altered the bacterial morphology, led to cytoplasmic leakage and membrane permeability deconstruction, ultimately resulting in hemolysis and death (Wei et al. 2016). ST subcritical water extracts (50 mg mL−1) had a highly effective scavenging effect on E. coli and B. cereus, and the minimum inhibitory concentration (0.625 mg mL−1) and minimum bactericidal concentration (1.25 mg mL−1) of E. coli were higher than those of B. cereus, which may result from the high levels of phenolic compounds (Park et al. 2022). Compared to other brown algae (Undaria pinnatifida, Saccharina japonica), ST had the strongest antimicrobial activity. At high concentrations (50 mg mL−1), the ST hydrolysate inhibited B. cereus and S. aureus with 18 mm and 22 mm, respectively, and Gram-negative bacteria (E. coli and Enterobacteriaceae) with 14 mm (Park et al. 2023).
Other effects
In addition to the activities mentioned above, other biological effects of ST have also been investigated, confirming its excellent skincare potential and promoting skin health (Lee et al. 2022). Overexpression of MMP-1, MMP-9, and tyrosinase-related protein 1 (TRP-1) is a major cause of skin pigmentation and elasticity loss (Wen et al. 2013, Van Pham et al. 2014). The optimized STE of 2 mg mL−1 (time 12.0 min, temperature 65.2°C, EtOH concentration 53.5%) effectively inhibited the mRNA expression of TRP-1, MMP-1 (inhibition rate 58.6%), and MMP-9 (inhibition rate 78.8%) in B16F10 cells (Gam et al. 2021). In addition, STE enhanced the viability of L929 cells stimulated by H2O2 stimulation and UV-B irradiation, elevated the functions of SOD, glutathione peroxidase, and total antioxidant capacity, decreased the malondialdehyde level, decreased the production of intracellular ROS. STE inhibited H2O2-induced inflammatory response by downregulating the expression of TNF-α, IL-6, COX-2, and iNOS, and inhibited collagenase and elastase activities and MMP-2 expression. STE on EpiSkin exposed to 5% sodium dodecyl sulfate for 15 min and latent for 42 h exceeds 50%, indicating that STE is non-corrosive to human skin. In addition, ST phenolic-rich extract can reduce ROS yields by 71, 71, and 85%, respectively (0.8, 1.2, and 1.6 μg mL−1) after irradiation of zebrafish embryos with UV-B (Chen et al. 2022, Cui et al. 2023).
Osteoblasts and osteoclasts are the two main functional cells in bone tissue that play a key role in bone formation and resorption, respectively (Chen et al. 2018). In the process of bone remodeling, they regulate each other through complex signaling pathways to maintain the homeostasis of bone tissue (Kim et al. 2020). Research has found that ST MeOH extract (100 μg mL−1) enhanced the differentiation of MC3T3-E1 osteoblasts by increasing osteocalcin, bone morphogenetic protein-2, and type I collagen amount, thereby increasing alkaline phosphatase activity (Kim et al. 2016). ST oligosaccharides effectively inhibited the formation of RAW264.7 osteoclasts and actin loops induced by receptor activator of NF-κB ligand (RANKL), effectively suppressed the upregulation of related genes (ATP60, c-Fos, DC-Stamp, NFATc1, and Trap) induced by RANKL in a time-dependent manner, and inhibited the formation of osteoclasts by inhibiting the IRF-8 degradation and disrupting NF-κB pathway initiation (Jin et al. 2023). It could be seen that ST has potential medicinal value for managing osteoporosis.
LOX is a key enzyme in lipid metabolism and plays an essential role in arachidonic acid metabolism by generating biologically active lipid mediators (Haeggstrom and Funk 2011). High levels of LOX can have several adverse health effects, increasing the risk of inflammation and cardiovascular-related diseases (Zhao and Funk 2004). Compounds HEP and HEH inhibited LOX in a dose-dependent manner with IC50 values of 40 and 5.0 μM, respectively, and both exhibit higher LOX suppressive effects than the known inhibitor nordihydroguaiaretic acid (IC50 = 400 μM) (Kurihara et al. 2014). Alzheimer’s disease (AD) is a highly age-related neurodegenerative disease, characterized by deposition of amyloid beta, abnormal phosphorylation of tau protein/neurofibrillary tangles, and decreased acetylcholine signaling. ST hot-water extract has a protective effect on D-galactose-induced aging rats in terms of memory and cognitive impairment, AD-related lesions, oxidative stress, and microglial activation. ST hot-water extract delayed the progression of AD by inhibiting glycogen synthase 3β activity, reducing the expression of hyperphosphorylated tau protein in the brain (Promyo et al. 2025). In addition, ST sulfated heteropolysaccharides showed neuroprotective activity against 6-hydroxydopamine-induced SH-SY5Y cells, which means that ST might be a good potential for the therapy of neurodegenerative diseases (Jin et al. 2018). Compounds isovariecolorin I, alkaloid E-7, and dihydroechinnulin exhibited strong mortality activity counter to brine shrimp (Artemia salina) and slight nematode killing activity oppose Panagrellus redivivus (Du et al. 2017). ST polysaccharides had strong inhibitory activity against glucosidase, and could enhance glucose uptake efficiency of HepG2 insulin-resistant cells in a concentration-dependent manner, and glucose consumption increased by 198.4% when the polysaccharide concentration was 1.0 mg mL−1 (Ren et al. 2017).
DEVELOPMENT AND APPLICATION
Over recent years, marine resources have gradually become an important area of concern for the research and development of new drugs and health foods due to their potential in the screening of bioactive compounds. Among them, seaweed, as food, feed, soil amendment, and medicinal raw materials, shows high commercial value and application prospects (Souza et al. 2012, Yang et al. 2021). Due to its rich bioactive ingredients and high nutritional value, ST has a wide array of application potential in the food, pharmaceutical, and nutraceutical industries (Liu et al. 2021). ST has been used in folk applications for centuries and is recognized in the capacity of a traditional Chinese medicine, having a long history of treating diseases dating back nearly 2,000 years (Liu et al. 2012, Rushdi et al. 2020). In China, ST was listed as a medium grade in the Shennong Ben Cao Jing, and was also recorded in ancient medical books such as Ming yi Bie lu and Ben cao Gang mu. ST can be used as one of the sources of traditional Chinese medicine Haicao/Haiqian, salty in flavor, cold in nature and attributive to the liver, stomach, and kidney meridians, which softens hardness and disperse the stagnated mass, clears away heat to resolve phlegm and induce diuresis, mainly treating goiter, sore throat, hypertension, hyperlipidemia, and other diseases (Jiang and Zhang 1993, Hu et al. 1998, Liu et al. 2012). According to the information in Donguibogam, a Korean textbook of Oriental Medicine, ST has been used for generations to treat edema and scrotal pain (Saraswati et al. 2019). In addition, this seaweed has long been used as an anthelmintic in Korean folk remedies (ji-chungie means this usage in Korean) (Yang et al. 2016). ST contains a large amount of protein, vitamins, and essential minerals and trace elements, and coastal residents have a tradition of eating ST, which have a long culinary history in China, Korea, and Japan (Ping et al. 2001). Under specific process conditions, ST can also be used as a new dietary fiber supplement source and an effective additive in nutritional health foods or cosmetics (Kang et al. 2019). ST leaves are fresh, tender, and soft, which have good functions and are recognized as a high-quality natural bait. ST is a refuge for crabs, mollusks, and silkworms to spawn and bait in the intertidal zone and subtidal zone. It is also an important economic resource and industrialized bait extraction for sea cucumber and abalone farming (Seo et al. 2011, Liu and Tan 2014, Li et al. 2022). Because of the high nutritional value of ST, the addition of 5% ST powder can significantly improve the non-specific immunity of turbot juveniles (Qiao et al. 2019).
ST exhibits rapid thallus growth and serves as a major component of seaweed beds, which is essential for maintaining the ecological balance of coastal ecosystems. ST has strong tolerance to abiotic stresses and can survive and grow in intertidal full-immersion artificial habitats, making it an ideal species for the construction of seaweed beds (Chu et al. 2012, Yu et al. 2012). ST has shown promise for bioremediation of marine pollution due to its capacity of adsorb heavy metal ions and alleviate eutrophication (Wu et al. 2010, Liu et al. 2014). The unsaturated fatty acids in ST have a strong algal killing effect on microalgae, with the lowest effective concentration below 5 mg L−1. The algal killing inhibition effect increases with the increase of unsaturated fatty acid concentration. ST can be used as an allelopathic substance to prevent and control various harmful microalgae (Wang et al. 2012). In addition, compounds phlorotannins and sulfoquinovosyl diacylglycerols were able to act as promoters of larval metamorphosis, and brown algae may play a vital role in the settlement/metamorphosis of marine animal larvae (Tsukamoto et al. 1994).
CONCLUSION AND PROSPECT
This article summarizes published papers on the physiology, chemistry, biological activity, and applications of Sargassum thunbergii. ST is a macroalgae in the northwest Pacific Ocean and plays an essential role in maintaining marine ecosystems, mainly found in the coastal waters of China, Korea, and Japan. So far, a variety of compounds have been isolated or identified from ST, with alkaloids and fatty acids accounting for the largest proportion. Studies have shown that ST is mainly reflected in anti-inflammatory, antioxidant, and anti-obesity effects. The biological activities of 15 compounds were reported, and it is worth noting that indole derivatives have strong and extensive biological activities against inflammation, antioxidation, and obesity.
Although current studies have shown the biological activity of ST, most studies are limited to the effect of the extract, and its intrinsic true bioactive ingredients and their toxicology and bioavailability in vivo are not yet clear. In addition, although it has been shown to have a high multi-faceted application value, its development and utilization are still under continuous research and development, and no related products have appeared on the market at present.
The main reason for this problem is due to the different growth regions, seasons, and organizational structure of ST, which leads to the uncontrollability of the harvest season and tissue part, yield, and effective ingredient content of raw materials. In the latest version of the Pharmacopoeia of the People’s Republic of China (2025), regulations containing Sargassum pallidum (Turn.) C. Ag. or Sargassum fusiforme (Harv.) Setch. as medicines of the same genus stipulate that the moisture content of the dried algae of both should not exceed 19.0%. Regulations on heavy metals and harmful elements: lead shall not exceed 5 mg kg−1, cadmium should not exceed 4 mg kg−1, mercury shall not exceed 0.1 mg kg−1, and copper shall not exceed 20 mg kg−1; Ethanol is used as solvent, and the extract shall not be less than 6.5%. In addition, the standard for active ingredients is measured in fucose (C6H12O5), which must be less than 1.70%. It also stipulates the preparation, characteristics, taste and meridians, functional indications, and dosage of both as medicinal decoction pieces (Chinese Pharmacopoeia Commission 2025). ST can use this as a reference to establish corresponding quality standards, standardize the operation of raw materials from harvesting to processing, ensure the safety, effectiveness, and consistency of ST, and enable ST to become a raw material for functional foods, drugs, cosmetics, etc.
In addition, the impact of ST on obesity deserves special attention. Changes in the environment and lifestyle, imbalance between energy intake and consumption, medications, and psychology in modern society may cause weight gain. Although ST has demonstrated strong anti-obesity activity, existing studies are still mainly limited to the cellular level and animal models, and there is a lack of clinical validation in populations. Therefore, it is necessary to carry out more systematic and in-depth research to evaluate its efficacy and safety in the human body, so as to provide solid theoretical support for the development of related new drugs or functional foods.
Notes
ACKNOWLEDGEMENTS
This research was supported by the Regional Innovation System & Education (RISE) program through the Jeju RISE Center, funded by the Ministry of Education (MOE) and the Jeju Special-Governing Province, Republic of Korea (2025-RISE-17-001).
CONFLICTS OF INTEREST
The authors declare that they have no potential conflicts of interest.