Macroalgal-Derived Bioactive Compounds as Anti-Inflammatory and Antioxidant Ingredients for Food and Nutraceutical Industry: Mechanisms, Functional Applications, and Challenges

Abstract

Marine-derived bioactive compounds have attracted considerable attention as functional ingredients for food and nutraceutical applications due to their various biological activities. Among marine resources, macroalgae represent a sustainable and abundant source of structurally diverse bioactive compounds, including polyphenols, pigments, and polysaccharides. This review provides a comprehensive overview of macroalgal bioactive compounds, with particular emphasis on their sources, the environmental and seasonal factors influencing their composition, chemical classification and characteristics, extraction technologies, biological properties and food and nutraceutical applications. Particularly, attention is given to the molecular mechanisms underlying their antioxidant and anti-inflammatory effects, including radical scavenging, metal chelation, modulation of endogenous antioxidant defense systems, and regulation of key signaling pathways involved in inflammation. Green extraction techniques and encapsulation strategies for improving the stability, bioavailability, and functionality of macroalgal bioactives are critically discussed. Current applications in foods and nutraceutical products are reviewed alongside the major challenges related to biomass variability, large-scale production, standardization, and regulatory compliance. Overall, macroalgal bioactive compounds represent a promising class of sustainable health-promoting ingredients, and continued advances in cultivation, processing, extraction technologies, formulation, and regulatory frameworks will be essential to support their broader industrial utilization.

1. Introduction

1.1. Background

In recent decades, marine environments have emerged as a promising source of structurally unique and biologically potent natural products with significant potential for use in the food, pharmaceutical, cosmetic, and nutraceutical industries. Among marine resources, macroalgae or seaweeds have attracted particular attention due to their abundance, sustainability, and rich content of bioactive compounds (BACs). In addition, macroalgae play important ecological roles in primary production, nutrient cycling, and habitat formation in coastal environments [1]. Adaptation to highly variable environmental conditions, such as fluctuations in salinity, temperature, light availability, nutrient concentrations, and pressure gradients, has driven the evolution of specialized metabolic pathways that enable macroalgae to survive under environmental stress. Consequently, macroalgae produce various BACs, including polyphenols, pigments, polysaccharides, and other metabolites that contribute to ecological adaptation and stress tolerance.

1.2. Research Significance

Many of these compounds exhibit potent antioxidant and anti-inflammatory properties. Numerous studies have shown that they can modulate oxidative stress and inflammatory processes through multiple mechanisms, including scavenging free radicals and other reactive species, regulating endogenous antioxidant defense systems, and influencing key cellular signaling pathways associated with inflammation [2,3]. Moreover, the composition of pigments, cell wall structure, and polysaccharide storage vary according to the taxonomic group of macroalgae (brown, red, or green algae) [4,5]. As the biochemical composition of macroalgae is highly dynamic and influenced by environmental and seasonal factors [6], the quantity and quality of BACs may vary considerably among species and harvesting conditions. Understanding these factors is essential for optimizing biomass cultivation and harvesting strategies, and for ensuring reproducible bioactive profiles suitable for industrial applications. Once biomass has been obtained, efficient extraction and purification of BACs become critical steps in their valorization and industrial use. Conventional solvent-based extraction (CE) methods are increasingly being combined with or replaced by advanced, environmentally friendly extraction technologies, e.g., microwave-assisted extraction (MAE), ultrasound-assisted extraction (UAE), and supercritical fluid extraction (SFE), which offer advantages in extraction efficiency, selectivity, reduced solvent consumption, shorter processing times, and improved sustainability [7,8]. Efficient extraction strategies are closely related to the chemical diversity and structural complexity of macroalgal BACs. These bioactives range from low- to high-molecular-weight compounds and often have unique structural features, such as halogen substitutions, specific sulfation patterns, and complex stereochemistry, which are associated with distinct mechanisms of action and enhanced antioxidant and anti-inflammatory properties [3,9,10]. Their chemical characterization is crucial for understanding structure–activity relationships and health-promoting effects. Given the central role of oxidative stress and chronic inflammation in the development of many non-communicable diseases, the pleiotropic mechanisms of action of macroalgal BACs have attracted considerable interest for their use as multifunctional ingredients in preventive nutrition and therapeutic applications [11,12]. However, despite their promising bioactivity, the practical application of many macroalgal bioactives is often limited by chemical instability and low bioavailability due to poor solubility, susceptibility to oxidation, or degradation during processing and storage. Encapsulation technologies have therefore emerged as valuable tools for protecting sensitive compounds from environmental stress, improving stability and bioavailability, and facilitating the incorporation of marine BACs into complex food and nutraceutical matrices. Various encapsulation approaches, including ionic gelation, chitosan-based nanoparticles, nanoemulsions, liposomes, freeze-dried microcapsules, and electrosprayed microcapsules, are being investigated to maximize the functional performance of macroalgal bioactives [13,14,15]. The choice of encapsulation technique depends on the chemical nature of the BAC and the intended application.

1.3. Aim and Scope of Review

Nevertheless, several challenges remain, including variability in raw materials, production costs, large-scale processing, regulatory compliance, and the need for further validation of biological efficacy and safety [13]. In this context, the present review offers a comprehensive overview of macroalgal-derived BACs, including polyphenols, pigments, and polysaccharides, emphasizing their sources, chemical classification, extraction techniques, and mechanisms of antioxidant and anti-inflammatory activity. It also addresses encapsulation strategies to enhance stability and functionality, explores functional applications in the food and nutraceutical industries, and discusses current challenges, regulatory aspects, and future perspectives. This review integrates recent scientific advances and technological developments to provide a comprehensive, up-to-date assessment of macroalgal-derived health-promoting compounds, evaluate their opportunities and limitations for sustainable use, and identify key challenges and future research directions for industrial applications.

1.4. Literature Search Strategy

The literature search was conducted using the Web of Science, Scopus, Google Scholar, and PubMed databases by applying various combinations of relevant keywords and Boolean operators to maximize the retrieval of pertinent studies. The identified records were screened for relevance to the scope of this review, with priority given to original research articles reporting experimental data on macroalgal composition and bioactive compounds, their chemical classification, extraction technologies, antioxidant and anti-inflammatory activities, encapsulation strategies, functional applications, and regulatory aspects. This review primarily focuses on studies published between January 2016 and June 2026. However, earlier seminal publications were also included where necessary to provide historical context and foundational knowledge. The selection process involved an initial screening of titles and abstracts, followed by a full-text evaluation of potentially relevant articles to ensure the inclusion of scientifically rigorous, high-quality, and relevant studies.

2. Marine Macroalgae as Sources of Bioactive Compounds

Macroalgae are a diverse group of multicellular marine organisms classified into three major phyla based on pigmentation: Phaeophyceae (brown); Chlorophyta (green); and Rhodophyta (red), each exhibiting distinct bioactive profiles [16]. According to AlgaeBase [17] red algae are the most diverse macroalgal group, comprising approximately 6000–7000 species, followed by brown algae with 2000–2200 species and green macroalgae with 900–1500 species. These groups are predominantly marine and include several ecologically and economically important orders: Gigartinales, Gracilariales, and Ceramiales in red algae; Fucales, Laminariales, and Dictyotales in brown algae; and Ulvales and Bryopsidales in green algae. Across these phyla, macroalgae are abundant sources of diverse BACs, including polyphenols, pigments, polysaccharides, lipids, proteins, and minerals [18]. Their sessile adaptation to dynamic marine conditions promotes the synthesis of secondary metabolites with pronounced antioxidant and anti-inflammatory properties, making them valuable ingredients for food and nutraceutical applications [19]. In addition, the increasing global production of cultivated algae and the approval of several macroalgal species as novel foods in the EU highlight their growing commercial relevance [20]. Nevertheless, the composition and concentration of BACs vary considerably among species and environmental conditions, highlighting the need to understand these factors to ensure biomass quality and support industrial utilization.

2.1. Environmental Factors Influencing Biochemical Composition of Marine Macroalgae

The bioactive composition of macroalgae shows substantial variability due to abiotic and biotic factors, species-specific traits, and post-harvest processing conditions (Figure 1). Abiotic factors such as geographical origin, seasonality, nutrient availability, temperature, light, UV radiation, and salinity strongly influence metabolic profiles, while biotic interactions, including grazing pressure and microbial associations, further modulate the synthesis of BACs [21]. In addition, inherent differences in metabolism and physiology among species also contribute to considerable variation in compound composition, even under similar environmental conditions. Furthermore, extraction conditions can significantly affect the yield and profile of detected compounds, as discussed in Section 4. Taken together, these environmental and biological factors drive the dynamic regulation of macroalgal metabolism. These natural fluctuations arise because macroalgae, as sessile organisms, activate sophisticated defense mechanisms in response to environmental stressors, producing secondary metabolites, such as polyphenols, pigments, and polysaccharides, when antioxidant protection or structural reinforcement is required [22]. This variability presents both challenges and opportunities for industrial applications, as understanding these patterns enables targeted harvest strategies, strain selection, and cultivation optimization to achieve consistent yields of nutraceutical-grade compounds.

2.1.1. Geographical Location

The geographical location of macroalgae influences their biochemical profiles due to differences in environmental conditions such as water temperature, salinity, and nutrient regimes. Studies have shown that the same species collected from different regions can exhibit significant variation in phenolic, pigment and polysaccharide content. For example, brown algae from higher latitudes, characterized by colder and nutrient-rich waters, often contain higher levels of phlorotannin polyphenols compared to those from warmer regions [23]. In a study of nine Antarctic brown and red seaweed species along a latitudinal gradient from the South Shetland Islands (~62° S) to Yalour Island (~65° S), chlorophyll concentration tended to increase with latitude [24]. Furthermore, significant differences in the yield of the sulfated polysaccharide fucoidan have been observed in Sargassum ilicifolium collected from five regions within the same sea area of Taiwan [25].

2.1.2. Seasonal Variation

Besides geographical location, seasonal variation is a major factor influencing macroalgal biochemical composition, reflecting the integrated effects of changes in temperature, irradiance, and nutrient availability throughout the year. In brown algae, phlorotannins typically reach their highest concentrations during summer. For example, in Ascophyllum nodosum levels increased from 0.6% in February to 2.2% in July [26], and in Fucus spiralis total phenolic content (TPC) increased from 49.170 mg GAE/g in spring to 308.634 mg GAE/g in summer [27]. Interestingly, a recent study showed that phlorotannin content in storm-cast Ascophyllum nodosum exceeded by 10% during July–August, displaying less pronounced seasonal fluctuations than in freshly harvested algae and highlighting the potential of both fresh and storm-cast biomass as sustainable sources of phlorotannins for food, cosmetic, and pharmaceutical application [28]. Similarly, in green algae such as Ulva lacinulata and Codium tomentosum, chlorophyll and carotenoid contents increase from winter to summer, reaching peak levels under enhanced light and nutrient availability, with chlorophyll content increasing by 33% in U. lacinulata and 57% in C. tomentosum [29]. In contrast, the carotenoid pigment fucoxanthin in the brown algae Sargassum horneri and Cystoseira hakodatensis reached its maximum concentration during winter [30]. Some red algae, such as Palmaria palmata, show increased phycobiliprotein accumulation (pigment–protein complexes) in autumn (September–November), while carotenoids and chlorophylls reach their maximum concentration in winter and minimum in summer, reflecting adaptation to reduced light conditions [31]. In four brown algae (Alaria esculenta, Fucus distichus, Laminaria digitata, and Saccharina latissima) and one red alga (Palmaria palmata), chlorophyll and the concentrations of the carotenoids fucoxanthin and violaxanthin were higher in August, whereas lutein and zeaxanthin levels were higher in June [32]. Seasonal effects are also evident in polysaccharide composition, as fucoidan content in brown algae Fucus serratus, Fucus vesiculosus, Ascophyllum nodosum, Cystoseira barbata, Cystoseira compressa, and Sargassum vulgare increases during autumn growth periods and declines in spring and winter [33,34] while the highest carrageenan content in red algae Mastocarpus stellatus was identified in August [35].

2.1.3. Nutrient Availability

Macroalgal growth and metabolic activity depend on the availability of macronutrients (e.g., nitrogen, phosphorus), micronutrients (e.g., iron, zinc,), and essential vitamins (e.g., vitamin B12) [36]. In Fucus vesiculosus collected from two sites differing in nitrogen availability, polyphenolic concentrations were consistently higher in algae from the low-nitrogen site compared to those from the high-nitrogen site [37]. Similarly, nitrogen enrichment resulted in reduced concentrations of phlorotannins in F. vesiculosus [38]. In the red alga Chondrus crispus, phosphorus availability does not significantly influence the content of photosynthetic pigments, whereas nitrogen plays a key regulatory role, with increased nitrogen availability enhancing pigment concentrations (chlorophyll a and phycobiliproteins) and nitrogen limitation leading to their reduction [39]. In the same study, the so-called “Neish effect” describes an inverse relationship between nutrient availability and carrageenan content, whereby increasing nitrogen availability decreases carrageenan content, while nitrogen limitation promotes its accumulation. A similar pattern was observed for phosphorus, where low phosphorus availability led to higher carrageenan content, whereas phosphorus enrichment reduced it [39].

2.1.4. Temperature

Besides nutrient availability, other environmental stressors, particularly temperature, strongly influence macroalgal metabolism and the production of BACs. Rising sea surface temperatures associated with global climate change, increasing by more than 0.1 °C per decade since the mid-20th century, have become a major driver of changes in macroalgal physiology, distribution, and biochemical composition [21]. High water temperature triggers white rot disease in Saccharina japonica, causing progressive pigment loss and frond whitening [40]. In Cystoseira crinita, TPC decreased at 30 °C compared to 25 °C, indicating that higher temperatures suppress phenolic accumulation [41]. In contrast, no direct effect of temperature on phlorotannin levels was observed in Sargassum patens [42]. In the brown alga Laminaria digitata, elevated temperature accelerated the depletion of the storage polysaccharide laminarin, with reductions of ~90% at 5 °C compared to ~40% at 0 °C over three months, indicating increased metabolic consumption under warmer conditions [43]. Similarly, in red algae Kappaphycus alvarezii, increasing temperatures from 28 °C to 40 °C reduced carrageenan and pigment yields [44].

2.1.5. Light Availability

Alongside temperature, light availability (intensity, quality, and UV radiation) strongly influences macroalgal growth and biochemical composition by regulating photosynthesis. Due to spatial and temporal variations in light conditions, macroalgae undergo photoadaptation by adjusting pigment composition, growth, respiration, and metabolism, which affects BAC synthesis [21]. Prolonged exposure to different light wavelengths reduced phlorotannin content in several brown algae species (Pelvetia canaliculata, Fucus vesiculosus, Ascophyllum nodosum, and Himanthalia elongate) [45]. Higher photon flux densities inhibited growth and reduced pigment content in red algae Bostrychia montagnei and B calliptera [46]. Higher irradiance reduced chlorophyll content and changed composition of oxygenated carotenoids in green algae Codium tomentosum and Bryopsis plumosa.

2.1.6. Salinity

Salinity affects algal osmotic balance and physiology, although tolerance varies among species. Most macroalgae thrive at salinities between 33 and 35 psu [21]. Among Arctic brown algae, some species remained stable across a wide salinity range, some exhibited pigment loss or high mortality under hyposaline conditions and some survived both low and high salinities but showed reduced photosynthetic activity [47]. In brown algae Ascophyllum nodosum and Fucus vesiculosus, reduced salinity led to a decrease in TPC and altered phenolic composition, with an increased proportion of cell wall-bound phenolics [48]. In Sargassum muticum, reduced salinity increased alginate polysaccharide content, while phlorotannin levels slightly increased at moderate salinity (20 ppt). Lower salinities (10–15 ppt) significantly reduced fucoxanthin, whereas only minor changes in chlorophyll a and carotenoids were observed [49].

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Pedisić, S.; Dukić, J.; Cegledi, E.; Dobrinčić, A.; Zorić, Z.; Pelaić, Z.; Garofulić, I.E.; Repajić, M.; Dragović-Uzelac, V. Macroalgal-Derived Bioactive Compounds as Anti-Inflammatory and Antioxidant Ingredients for Food and Nutraceutical Industry: Mechanisms, Functional Applications, and Challenges. Mar. Drugs 2026, 24, 254. https://doi.org/10.3390/md24070254