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A special issue of Marine Drugs (ISSN 1660-3397). This special issue belongs to the section "Marine-Derived Ingredients for Drugs, Cosmeceuticals and Nutraceuticals".

Deadline for manuscript submissions: closed (15 March 2025) | Viewed by 27865

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Special Issue Editors

Dr. Xiaxia Di

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Guest Editor

Norwegian Institute for Water Research, Oslo, Norway
Interests: algae; biomass; marine natural products; anti-inflammatory; bioactivity; biotechnology
Special Issues, Collections and Topics in MDPI journals

Dr. Margarida Costa

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Guest Editor

NIVA—Norsk Institutt for Vannforskning/Norwegian Institute for Water Research, Oslo, Norway
Interests: microalgae; high-value biomass; secondary metabolites; bioactivity; biomass applications

Special Issue Information

Dear Colleagues,

Microalgae and macroalgae have drawn increasing research interest over the last few decades due to their abilities to produce high-value products such as carotenoids, lipids, carbohydrates, vitamins, and proteins. They have become popular from both application and fundamental points of view as high-value compounds that can be applied in the formulation of numerous bioproducts such as nutraceuticals, animal feed, agriculture biofertilizers, cosmetics, biomedicine, and textile products. However, only a minute fraction of algae has been investigated and developed into applications. Given the vast taxonomic diversity of algae, most have not yet been explored, and therefore, we do not currently have full understanding of the associated chemical diversity. Hence, it is essential to expand upon the current paradigm in research to assess the potential of algae.

Therefore, we have organized this Special Issue “High-Value Algal Products” with the aim of collecting original research articles and review papers which focus on high-value products derived from microalgae and macroalgae. We welcome work on strain identification, culture optimization, and the extraction, isolation, structure elucidation, and potential application of high-value products.

Dr. Xiaxia Di
Dr. Margarida Costa
Guest Editors

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Keywords

seaweed
microalgae
biochemical composition
cultivation
industrial application
biotechnology
biomass
biological activity

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Published Papers (11 papers)

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Research

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11 pages, 4104 KiB

Open AccessArticle

Lithium Coupled with C6-Carboxyl Improves the Efficacy of Oligoguluronate in DSS-Induced Ulcerative Colitis in C57BL/6J Mice

by Jiayi Li, Meng Shao, Hao Liu, Peng Guo, Fei Liu, Mingfeng Ma and Quancai Li

Mar. Drugs 2024, 22(12), 573; https://doi.org/10.3390/md22120573 - 21 Dec 2024

Viewed by 973

Abstract

Oligoguluronate lithium (OGLi) was prepared for the purpose of enhancing the anti-ulcerative colitis (UC) activities of OG, in which lithium (Li⁺) is coupled with the C6-carboxyl of G residue. The therapeutic effects of OGLi on dextran sulfate (DSS)-induced UC mice were investigated, and oligoguluronate sodium (OGNa) and lithium carbonate (LC) were used as contrasts. The effects of OGLi, OGNa and LC on the treatment of UC mice were studied by monitoring body weight change and evaluating colon length, the disease activity index (DAI), histopathological examination and gut microbiota regulation. The results showed that compared with OGNa and LC, OGLi significantly reduced the clinical symptoms and histopathological changes associated with UC in the acute model. It was worth noting that OGLi significantly changed the gut microbiota characteristics of the DSS-treated mice and corrected the typical dysbacteriosis of DSS-induced UC. This intervention resulted in increasing the abundance of norank_f_Muribaculaceae and Ileibacterium spp. while reducing the levels of Escherichia-Shigella spp. and Romboutsia spp. The OGLi could significantly increase the diversity of intestinal microorganisms in the short term. All of these discoveries demonstrate that lithium collaboratively enhances the anti-UC efficacy of OG, which will help to create OG-based drugs for the treatment of UC. Full article

(This article belongs to the Special Issue High-Value Algae Products)

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15 pages, 2194 KiB

Open AccessArticle

Comparative Analysis of the Biochemical and Molecular Responses of Nannochloropsis gaditana to Nitrogen and Phosphorus Limitation: Phosphorus Limitation Enhances Carotenogenesis

by Sun Young Kim, Hanbi Moon, Yong Min Kwon, Kyung Woo Kim and Jaoon Young Hwan Kim

Mar. Drugs 2024, 22(12), 567; https://doi.org/10.3390/md22120567 - 18 Dec 2024

Cited by 1 | Viewed by 1418

Abstract

Nannochloropsis gaditana is well known for its potential for biofuel production due to its high lipid content. Numerous omics and biochemical studies have explored the overall molecular mechanisms underlying the responses of Nannochloropsis sp. to nutrient availability, primarily focusing on lipid metabolism. However, N. gaditana is able to synthesize other valuable products such as carotenoids, including violaxanthin, which has various biological functions and applications. In this study, we comparatively investigated the physiological, biochemical, and molecular responses of N. gaditana to nitrogen and phosphorus limitation, examining biomass production, photosynthetic activity, lipid, chlorophyll, and carotenoids content, and RNA-seq data. Nitrogen limitation decreased photosynthetic activity, chlorophyll content, and biomass production but increased lipid content. Phosphorus limitation substantially increased carotenoids content, with violaxanthin productivity of 10.24 mg/L, 3.38-fold greater than under the control condition, with little effect on biomass production or photosynthetic function. These results were generally consistent with the gene expression pattern observed in transcriptomic analysis. This integrated analysis shows that phosphorus limitation can be an economically competitive solution by enhancing valuable carotenoids while maintaining lipid and biomass production in N. gaditana. Full article

(This article belongs to the Special Issue High-Value Algae Products)

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19 pages, 2361 KiB

Open AccessArticle

Nannochloropsis oceanica as a Source of Bioactive Compounds: Mapping the Effects of Cultivation Conditions on Biomass Productivity and Composition Using Response Surface Methodology

by Emil Gundersen, Jette Jakobsen, Susan Løvstad Holdt and Charlotte Jacobsen

Mar. Drugs 2024, 22(11), 505; https://doi.org/10.3390/md22110505 - 6 Nov 2024

Cited by 2 | Viewed by 3181

Abstract

Microalga Nannochloropsis oceanica presents a promising source of high-value food ingredients such as protein, omega-3 fatty acids, and vitamins. To fully unlock its potential, a thorough understanding of how cultivation conditions affect both growth and the nutritional composition is required. Hence, this study aimed to test and model the effects of temperature, light intensity, and salinity on biomass productivity and the final contents of protein, eicosapentaenoic acid (EPA), and vitamin K₂ using response surface methodology (RSM). The RSM experiment revealed that the highest temperature and light intensity tested favored biomass productivity and protein content. According to the generated models, the two responses peaked with 0.135 g DM·L⁻¹·day⁻¹ and 0.559 g·g⁻¹ DM, respectively, at 27 °C and 300–350 µmol·m⁻²·s⁻¹. In contrast, the contents of both EPA and menaquinone-4 (MK-4), the only detected K vitamer, were stimulated at the lowest tested temperature. Based on the generated models, the two responses peaked with 0.037 g·g⁻¹ DM and 89.3 µg·g⁻¹ DM, respectively, at 19 °C combined with 3.0% salinity (EPA) or 120 µmol·m⁻²·s⁻¹ (MK-4). Although additional optima may exist beyond the tested conditions, these findings provide valuable information on N. oceanica’s cellular response to changes in key cultivation conditions. Furthermore, it shows that two-stage cultivation may be needed to fully unlock the potential of this microalga as a future source of valuable lipid ingredients. Full article

(This article belongs to the Special Issue High-Value Algae Products)

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15 pages, 4007 KiB

Open AccessArticle

Effect of Reactive Oxygen Species Photoproduced in Different Water Matrices on the Photostability of Gadusolate and Mycosporine-Serinol

by Martin George Thomas, Sylvie Blanc, Mickael Le Bechec, Thierry Pigot and Susana C. M. Fernandes

Mar. Drugs 2024, 22(10), 473; https://doi.org/10.3390/md22100473 - 16 Oct 2024

Viewed by 1435

Abstract

In the past few years, there has been an increasing interest in mycosporines—UV-absorbing molecules—bringing important insights into their intrinsic properties as natural sunscreens. Herein, mycosporine-serinol and gadusol (enolate form)/gadusolate were exposed to UV radiation via a solar simulator and the photostability was assessed in pure water and different natural matrices like river, estuary and ocean water. In general, this study revealed that the photodegradation of gadusolate and mycosporine-serinol was higher in natural matrices than in pure water due to the generation of singlet oxygen on UV irradiation. In pure water, in terms of photostability, both gadusolate and mycosporine-serinol were found to offer good protection and high performance in terms of photodegradation quantum yield ((0.8 ± 0.2) × 10⁻⁴ and (1.1 ± 0.6) × 10⁻⁴, respectively). Nonetheless, the photostability of mycosporine-serinol was found to be superior to that of gadusolate in natural water, namely, ocean, estuary and river. The present work highlights how mycosporine-serinol and gadusolate resist photodegradation, and supports their role as effective and stable UV-B sunscreens. Full article

(This article belongs to the Special Issue High-Value Algae Products)

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25 pages, 3187 KiB

Open AccessArticle

Characterization of Unfractionated Polysaccharides in Brown Seaweed by Methylation-GC-MS-Based Linkage Analysis

by Barinder Bajwa, Xiaohui Xing, Spencer C. Serin, Maria Hayes, Stephanie A. Terry, Robert J. Gruninger and D. Wade Abbott

Mar. Drugs 2024, 22(10), 464; https://doi.org/10.3390/md22100464 - 9 Oct 2024

Cited by 3 | Viewed by 4210

Abstract

This study introduces a novel approach to analyze glycosidic linkages in unfractionated polysaccharides from alcohol-insoluble residues (AIRs) of five brown seaweed species. GC-MS analysis of partially methylated alditol acetates (PMAAs) enables monitoring and comparison of structural variations across different species, harvest years, and tissues with and without blanching treatments. The method detects a wide array of fucose linkages, highlighting the structural diversity in glycosidic linkages and sulfation position in fucose-containing sulfated polysaccharides. Additionally, this technique enhances cellulose quantitation, overcoming the limitations of traditional monosaccharide composition analysis that typically underestimates cellulose abundance due to incomplete hydrolysis of crystalline cellulose. The introduction of a weak methanolysis-sodium borodeuteride reduction pretreatment allows for the detection and quantitation of uronic acid linkages in alginates. Full article

(This article belongs to the Special Issue High-Value Algae Products)

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16 pages, 3297 KiB

Open AccessArticle

Brown Algae Ecklonia cava Extract Modulates Adipogenesis and Browning in 3T3-L1 Preadipocytes through HO-1/Nrf2 Signaling

by Indyaswan T. Suryaningtyas, Dae-Sung Lee and Jae-Young Je

Mar. Drugs 2024, 22(8), 330; https://doi.org/10.3390/md22080330 - 23 Jul 2024

Cited by 2 | Viewed by 1956

Abstract

This study explores the anti-obesity effects of the ethyl acetate extract of Ecklonia cava (EC-ETAC) on 3T3-L1 preadipocytes, focusing on its impact on adipogenesis, lipolysis, and adipose browning via the HO-1/Nrf2 pathway. Western blot analysis revealed that EC-ETAC significantly inhibited adipogenic transcription factors (PPARγ, C/EBPα, SREBP-1) and lipogenesis-related proteins (FAS, LPL). Concurrently, EC-ETAC enhanced lipolytic markers (p-AMPK, p-HSL) and adipose browning-related proteins (UCP-1, PGC-1α), indicating its role in promoting lipolysis and adipose browning. The inhibition of HO-1 by zinc protoporphyrin (ZnPP) significantly reversed these effects, underscoring the critical role of HO-1 in mediating the anti-obesity properties of EC-ETAC. Additionally, fluorescence measurements and Oil Red O staining confirmed the reduction of lipid accumulation and oxidative stress upon EC-ETAC treatment. These findings suggest that EC-ETAC exerts its anti-obesity effects by modulating the HO-1/Nrf2 pathway, which is crucial for regulating adipogenesis, lipolysis, and adipose browning. This study highlights the potential of EC-ETAC as a natural therapeutic agent for obesity management and supports further research into its clinical applications. By targeting the HO-1/Nrf2 pathway, EC-ETAC could offer a novel approach to enhancing energy expenditure and reducing fat mass, thereby improving metabolic health. Full article

(This article belongs to the Special Issue High-Value Algae Products)

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15 pages, 1335 KiB

Open AccessArticle

Chemical and Antioxidant Properties of Solvent and Enzyme-Assisted Extracts of Fucus vesiculosus and Porphyra dioica

by Paulo Nova, Sara A. Cunha, Ana R. Costa-Pinto and Ana Maria Gomes

Mar. Drugs 2024, 22(7), 319; https://doi.org/10.3390/md22070319 - 18 Jul 2024

Cited by 2 | Viewed by 1773

Abstract

Extraction strategies impact the efficiency and nature of extracted compounds. This work assessed the chemical composition and antioxidant capacity of ethanolic, hydroethanolic, and aqueous versus enzyme-assisted extracts (isolated or with the sequential use of alcalase^®, cellulase^®, and viscozyme^®) of the macroalgae Fucus vesiculosus (brown, Phaeophyceae) and Porphyra dioica (red, Rhodophyta. For both macroalgae, enzyme-assisted extraction (EAE) was the most efficient process compared to solvent-assisted extraction (SAE), independent of solvent. Fucus vesiculosus extraction yields were higher for EAE than for SAE (27.4% to 32.2% and 8.2% to 30.0%, respectively). Total phenolics content (TPC) was at least 10-fold higher in EAE extracts (229.2 to 311.3 GAE/g_extract) than in SAE (4.34 to 19.6 GAE/g_extract) counterparts and correlated well with antioxidant capacity (ABTS and ORAC methods), with EAE achieving values up to 8- and 2.6-fold higher than those achieved by SAE, respectively. Porphyra dioica followed F. vesiculosus’s trend for extraction yields (37.5% to 51.6% for EAE and 5.7% to 35.1% for SAE), TPC, although of a lower magnitude, (0.77 to 8.95 GAE/g_extract for SE and 9.37 to 14.73 GAE/g_extract for EAE), and antioxidant capacity. Aqueous extracts registered the highest DPPH values for both macroalgae, with 2.3 µmol TE/g_extract and 13.3 µmol TE/g_extract for F. vesiculosus and P. dioica, respectively. EAE was a more efficient process in the extraction of soluble protein and reducing sugars in comparison to SAE. Furthermore, an improved effect of enzyme-assisted combinations was observed for almost all analyzed parameters. This study shows the promising application of enzyme-assisted extraction for the extraction of valuable compounds from F. vesiculosus and P.dioica, making them excellent functional ingredients for a wide range of health and food industrial applications. Full article

(This article belongs to the Special Issue High-Value Algae Products)

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19 pages, 2677 KiB

Open AccessArticle

Optimizing the Extraction of Bioactive Compounds from Porphyra linearis (Rhodophyta): Evaluating Alkaline and Enzymatic Hydrolysis for Nutraceutical Applications

by Débora Tomazi Pereira, Paz García-García, Nathalie Korbee, Julia Vega, Francisco J. Señoráns and Félix L. Figueroa

Mar. Drugs 2024, 22(6), 284; https://doi.org/10.3390/md22060284 - 18 Jun 2024

Cited by 2 | Viewed by 4338

Abstract

Porphyra sensu lato is one of the most economically significant and widely cultured and consumed algae in the world. Porphyra species present excellent nutraceutic properties due to their bioactive compounds (BACs). This research aimed to find the most efficient aqueous extraction method for BACs by examining alkaline and enzymatic hydrolysis. Alkaline hydrolysis with 2.5% sodium carbonate (SC) and at 80 °C proved optimal for extracting all BACs (phycobiliproteins, soluble proteins, polyphenols, and carbohydrates) except mycosporine-like amino acids (MAAs), which were best extracted with water only, and at 80 °C. Enzymatic hydrolysis, particularly with the ‘Miura’ enzymatic cocktail (cellulase, xylanase, glycoside hydrolase, and β-glucanase), showed superior results in extracting phycoerythrin (PE), phycocyanin (PC), soluble proteins, and carbohydrates, with increases of approximately 195%, 510%, 890%, and 65%, respectively, compared to the best alkaline hydrolysis extraction (2.5% SC and 80 °C). Phenolic content analysis showed no significant difference between the ‘Miura’ cocktail and 2.5% SC treatments. Antioxidant activity was higher in samples from alkaline hydrolysis, while extraction of MAAs showed no significant difference between water-only and ‘Miura’ treatments. The study concludes that enzymatic hydrolysis improves the efficiency of BACs extraction in P. linearis, highlighting its potential for the nutraceutical industry, and especially with respect to MAAs for topical and oral UV-photoprotectors. Full article

(This article belongs to the Special Issue High-Value Algae Products)

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Review

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34 pages, 1495 KiB

Open AccessReview

Nannochloropsis Lipids and Polyunsaturated Fatty Acids: Potential Applications and Strain Improvement

by Sofia Navalho, Narcis Ferrer-Ledo, Maria J. Barbosa and João Varela

Mar. Drugs 2025, 23(3), 128; https://doi.org/10.3390/md23030128 - 15 Mar 2025

Cited by 1 | Viewed by 1126

Abstract

The genus Nannochloropsis comprises a group of oleaginous microalgae that accumulate polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid (EPA). These molecules are essential for the correct development and health of humans and animals. Thanks to their attractive lipid profile, Nannochloropsis is mainly marketed as a feed ingredient in aquaculture. In microalgae of this genus, contents and cellular location of PUFAs are affected by the growth conditions and gene expression. Strain improvement through non-recombinant approaches can generate more productive strains and efficient bioprocesses for PUFA production. Nevertheless, the lack of specific markers, detection methods, and selective pressure for isolating such mutants remains a bottleneck in classical mutagenesis approaches or lipid quality assessment during cultivation. This review encompasses the importance of PUFAs and lipid classes from Nannochloropsis species and their potential applications. Additionally, a revision of the different ways to increase PUFA content in Nannochloropsis sp. by using classical mutagenesis and adaptive laboratory evolution is also presented, as well as various methods to label and quantify lipids and PUFAs from Nannochloropsis microalgae. Full article

(This article belongs to the Special Issue High-Value Algae Products)

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59 pages, 4856 KiB

Open AccessReview

Extraction and Analytical Methods for the Characterization of Polyphenols in Marine Microalgae: A Review

by Gabriela Bermudez, Cristina Terenzi, Francesca Medri, Vincenza Andrisano and Serena Montanari

Mar. Drugs 2024, 22(12), 538; https://doi.org/10.3390/md22120538 - 30 Nov 2024

Cited by 2 | Viewed by 2036

Abstract

Marine microalgae are emerging as promising sources of polyphenols, renowned for their health-promoting benefits. Recovering polyphenols from microalgae requires suitable treatment and extraction techniques to ensure their release from the biomass and analytical methodologies to assess their efficiency. This review provides a comprehensive comparison of traditional and cutting-edge extraction and analytical procedures applied for polyphenolic characterization in marine microalgae over the past 26 years, with a unique perspective on optimizing their recovery and identification. It addresses (I) cell disruption techniques, including bead milling, high-speed homogenization, pulsed electric field, ultrasonication, microwave, freeze-thawing, and enzymatic/chemical hydrolysis; (II) extraction techniques, such as solid–liquid extraction, ultrasound and microwave-assisted extraction, pressurized-liquid extraction, and supercritical CO₂; (III) analytical methods, including total phenolic and flavonoid content assays and advanced chromatographic techniques like GC-MS, HPLC-DAD, and HPLC-MS. Key findings showed bead milling and chemical hydrolysis as effective cell disruption techniques, pressurized-liquid extraction and microwave-assisted extraction as promising efficient extraction methods, and HPLC-MS as the finest alternative for precise phenolic characterization. Unlike previous reviews, this study uniquely integrates both extractive and analytical approaches in one work, focusing exclusively on marine microalgae, a relatively underexplored area compared to freshwater species, offering actionable insights to guide future research and industrial applications. Full article

(This article belongs to the Special Issue High-Value Algae Products)

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24 pages, 2371 KiB

Open AccessReview

Microalgal Phenolics: Systematic Review with a Focus on Methodological Assessment and Meta-Analysis

by Vasilis Andriopoulos and Michael Kornaros

Mar. Drugs 2024, 22(10), 460; https://doi.org/10.3390/md22100460 - 7 Oct 2024

Cited by 2 | Viewed by 4366

Abstract

A critical review and analysis of the literature relevant to the phenolic content of eucaryotic microalgae was performed. Several issues were identified and discussed. In summary, the main problems with the reporting on the phenolic content of microalgae are the following: (1) despite its usefulness in the determination of phenolic content in plant samples, the Folin–Ciocalteu assay is non-suitable for microalgal research due to the high presence of interfering compounds in microalgal extracts such as chlorophyll and its derivatives in organic extracts and free aromatic amino acids or nucleotides in aqueous extracts; (2) while there is chromatographic evidence for the presence of simple phenolic acids in most microalgal clades, the lack of critical enzymes of phenolic biosynthesis in most microalgae, as well as the high variability of phenolic profiles even in the same genus, require more extensive research before conclusions are drawn; (3) the accumulation and metabolism of external phenolics by microalgae has been almost universally neglected in studies focusing on the phenolic content of microalgae, even when natural seawater or complex organic media are used in the cultivation process. Despite these issues, the literature focusing on the bioremediation of waste streams rich in phenolics through microalgae demonstrates the ability of those organisms to adsorb, internalize, and in many cases oxidize or transform a wide range of phenolic compounds, even at very high concentrations. Simple phenolics found in waste streams, such as olive mill waste, have been shown to enhance the antioxidant activity and various bioactivities of microalgal extracts, while complex biotransformation products of phenolics have also been characterized. In conclusion, the de novo biosynthesis of phenolic compounds via eucaryotic microalgae requires further investigation with better designed experiments and suitable analytical methods, while the response of microalgae to phenolic compounds in their growth medium is of great practical interest, both in terms of waste treatment and for the production of functional foods, cosmetics, and pharmaceuticals. Full article

(This article belongs to the Special Issue High-Value Algae Products)

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