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Special Issue "Bioactive Compounds Derived from Marine Microalgae"

A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: closed (20 December 2019) | Viewed by 51705

Special Issue Editors

Dr. Giovanna Romano
E-Mail Website
Guest Editor
Marine Biotechnology Department, Stazione Zoologica Anton Dohrn, Naples, Italy
Interests: bioactive metabolites from marine organisms for pharmaceutical; nutraceutical and cosmeceutical applications; novel strategies to identify marine-derived compounds; including -omic approaches
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Marine microalgae are an excellent source of carotenoids, lipids and ω-3 fatty acids, polysaccharides and vitamins, as well as being known producers of potent neurotoxins.

Many of these microalgal compounds already find applications as nutraceuticals and food supplements, although increasing reports attest to the discovery of anti-cancer, immunomodulatory and antimicrobial compounds from lab-cultured species.

Drug discovery from cultivable microorganisms represents a more environmentally-friendly approach allowing us to overcome the exploitation of marine resources by means of destructive collection practices; for this reason the search for bioactive compounds from marine microalgae is  attracting a great deal of attention.

Following our previous Special Issue on ‘Marine Microalgae’, we encourage the submission of research papers and reviews focused on bioactive compounds isolated from marine microalgae or inspired by natural compounds and produced by synthesis, highlighting novel structural features and bioactivities, from in vitro studies to biotechnological applications.

Dr. Adele Cutignano
Dr. Giovanna Romano
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Marine Drugs is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Bioactive molecules
  • Drug discovery
  • Structural characterization
  • Secondary metabolites
  • Biological activity
  • Microalgae

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Published Papers (12 papers)

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Research

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Article
Ectoine from Bacterial and Algal Origin Is a Compatible Solute in Microalgae
Mar. Drugs 2020, 18(1), 42; https://doi.org/10.3390/md18010042 - 06 Jan 2020
Cited by 27 | Viewed by 3453
Abstract
Osmoregulation in phytoplankton is attributed to several highly polar low-molecular-weight metabolites. A widely accepted model considers dimethylsulfoniopropionate (DMSP) as the most important and abundant osmotically active metabolite. Using an optimized procedure for the extraction and detection of highly polar metabolites, we expand the [...] Read more.
Osmoregulation in phytoplankton is attributed to several highly polar low-molecular-weight metabolites. A widely accepted model considers dimethylsulfoniopropionate (DMSP) as the most important and abundant osmotically active metabolite. Using an optimized procedure for the extraction and detection of highly polar metabolites, we expand the group of phytoplankton osmolytes by identifying ectoine in several microalgae. Ectoine is known as a bacterial compatible solute, but, to the best of our knowledge, was never considered as a phytoplankton-derived product. Given the ability of microalgae to take up zwitterions, such as DMSP, we tested the hypothesis that the algal ectoine is derived from associated bacteria. We therefore analyzed methanol extracts of xenic and axenic cultures of two different species of microalgae and could detect elevated concentrations of ectoine in those that harbor associated bacteria. However, also microalgae without an associated microbiome contain ectoine in smaller amounts, pointing towards a dual origin of this metabolite in the algae from their own biosynthesis as well as from uptake. We also tested the role of ectoine in the osmoadaptation of microalgae. In the model diatoms Thalassiosira weissflogii and Phaeodactylum tricornutum, elevated amounts of ectoine were found when cultivated in seawater with salinities of 50 PSU compared to the standard culture conditions of 35 PSU. Therefore, we add ectoine to the family of osmoadaptive metabolites in phytoplankton and prove a new, potentially synergistic metabolic interplay of bacteria and algae. Full article
(This article belongs to the Special Issue Bioactive Compounds Derived from Marine Microalgae)
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Article
Protective Action of Ostreococcus Tauri and Phaeodactylum Tricornutum Extracts towards Benzo[a]Pyrene-Induced Cytotoxicity in Endothelial Cells
Mar. Drugs 2020, 18(1), 3; https://doi.org/10.3390/md18010003 - 18 Dec 2019
Cited by 4 | Viewed by 2159
Abstract
Marine microalgae are known to be a source of bioactive molecules of interest to human health, such as n-3 polyunsaturated fatty acids (n-3 PUFAs) and carotenoids. The fact that some of these natural compounds are known to exhibit anti-inflammatory, antioxidant, [...] Read more.
Marine microalgae are known to be a source of bioactive molecules of interest to human health, such as n-3 polyunsaturated fatty acids (n-3 PUFAs) and carotenoids. The fact that some of these natural compounds are known to exhibit anti-inflammatory, antioxidant, anti-proliferative, and apoptosis-inducing effects, demonstrates their potential use in preventing cancers and cardiovascular diseases (CVDs). Benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon (PAH), is an ubiquitous environmental pollutant known to contribute to the development or aggravation of human diseases, such as cancer, CVDs, and immune dysfunction. Most of these deleterious effects are related to the activation of the polycyclic aromatic hydrocarbon receptor (AhR). In this context, two ethanolic microalgal extracts with concentrations of 0.1 to 5 µg/mL are tested, Ostreoccoccus tauri (OT) and Phaeodactylum tricornutum (PT), in order to evaluate and compare their potential effects towards B[a]P-induced toxicity in endothelial HMEC-1 cells. Our results indicate that the OT extract can influence the toxicity of B[a]P. Indeed, apoptosis and the production of extracellular vesicles were decreased, likely through the reduction of the expression of CYP1A1, a B[a]P bioactivation enzyme. Furthermore, the B[a]P-induced expression of the inflammatory cytokines IL-8 and IL1-β was reduced. The PT extract only inhibited the expression of the B[a]P-induced cytokine IL-8 expression. The OT extract therefore seems to be a good candidate for counteracting the B[a]P toxicity. Full article
(This article belongs to the Special Issue Bioactive Compounds Derived from Marine Microalgae)
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Article
Monoacylglycerides from the Diatom Skeletonema marinoi Induce Selective Cell Death in Cancer Cells
Mar. Drugs 2019, 17(11), 625; https://doi.org/10.3390/md17110625 - 01 Nov 2019
Cited by 9 | Viewed by 2350
Abstract
Microalgae are an excellent source of valuable compounds for nutraceutical and cosmeceutical applications. These photosynthesizing microorganisms are amenable for large-scale production, thus overcoming the bottleneck of biomass supply for chemical and activity characterization of bioactive compounds. This characteristic has recently also prompted the [...] Read more.
Microalgae are an excellent source of valuable compounds for nutraceutical and cosmeceutical applications. These photosynthesizing microorganisms are amenable for large-scale production, thus overcoming the bottleneck of biomass supply for chemical and activity characterization of bioactive compounds. This characteristic has recently also prompted the screening of microalgae for potential pharmaceutical applications. Here, we show that monoacylglycerides (MAGs) purified from the marine diatom Skeletonema marinoi have selective cytotoxic activity against the haematological cancer cell line U-937 and colon cancer cell line HCT-116 compared to normal MePR-2B cells. LC-MS analysis of the raw extract revealed that in their natural form, MAGs occur as 2-monoacyl derivatives and include mainly C16 and C20 analogues, but they are converted into the corresponding 1-isomers during purification processes. Pure compounds along with the synthetic 1-monoarachidonoylglycerol tested on HCT-116 and U-937 tumor cell lines induced cell death via apoptosis. The mechanism of action was investigated, and we show that it involves the induction of apoptosis through caspase 3/7 activation. These findings pave the way for the possible use of these molecules as potential anticancer agents or as precursors for the generation of new and more potent and selective compounds against tumor cells. Full article
(This article belongs to the Special Issue Bioactive Compounds Derived from Marine Microalgae)
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Article
Effects of Temperature, Growth Media, and Photoperiod on Growth and Toxin Production of Azadinium spinosum
Mar. Drugs 2019, 17(9), 489; https://doi.org/10.3390/md17090489 - 22 Aug 2019
Cited by 11 | Viewed by 2272
Abstract
Azaspiracids (AZAs) are microalgal toxins that can accumulate in shellfish and lead to human intoxications. To facilitate their study and subsequent biomonitoring, purification from microalgae rather than shellfish is preferable; however, challenges remain with respect to maximizing toxin yields. The impacts of temperature, [...] Read more.
Azaspiracids (AZAs) are microalgal toxins that can accumulate in shellfish and lead to human intoxications. To facilitate their study and subsequent biomonitoring, purification from microalgae rather than shellfish is preferable; however, challenges remain with respect to maximizing toxin yields. The impacts of temperature, growth media, and photoperiod on cell densities and toxin production in Azadinium spinosum were investigated. Final cell densities were similar at 10 and 18 °C, while toxin cell quotas were higher (~3.5-fold) at 10 °C. A comparison of culture media showed higher cell densities and AZA cell quotas (2.5–5-fold) in f10k compared to f/2 and L1 media. Photoperiod also showed differences, with lower cell densities in the 8:16 L:D treatment, while toxin cell quotas were similar for 12:12 and 8:16 L:D treatments but slightly lower for the 16:8 L:D treatment. AZA1, -2, and -33 were detected during the exponential phase, while some known and new AZAs were only detected once the stationary phase was reached. These compounds were additionally detected in field water samples during an AZA event. Full article
(This article belongs to the Special Issue Bioactive Compounds Derived from Marine Microalgae)
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Article
Light Intensity and Nitrogen Concentration Impact on the Biomass and Phycoerythrin Production by Porphyridium purpureum
Mar. Drugs 2019, 17(8), 460; https://doi.org/10.3390/md17080460 - 07 Aug 2019
Cited by 20 | Viewed by 3900
Abstract
Several factors have the potential to influence microalgae growth. In the present study, nitrogen concentration and light intensity were evaluated in order to obtain high biomass production and high phycoerythrin accumulation from Porphyridium purpureum. The range of nitrogen concentrations evaluated in the [...] Read more.
Several factors have the potential to influence microalgae growth. In the present study, nitrogen concentration and light intensity were evaluated in order to obtain high biomass production and high phycoerythrin accumulation from Porphyridium purpureum. The range of nitrogen concentrations evaluated in the culture medium was 0.075–0.450 g L−1 and light intensities ranged between 30 and 100 μmol m−2 s−1. Surprisingly, low nitrogen concentration and high light intensity resulted in high biomass yield and phycoerythrin accumulation. Thus, the best biomass productivity (0.386 g L−1 d−1) and biomass yield (5.403 g L−1) were achieved with NaNO3 at 0.075 g L−1 and 100 μmol m−2 s−1. In addition, phycoerythrin production was improved to obtain a concentration of 14.66 mg L−1 (2.71 mg g−1 of phycoerythrin over dry weight). The results of the present study indicate that it is possible to significantly improve biomass and pigment production in Porphyridium purpureum by limiting nitrogen concentration and light intensity. Full article
(This article belongs to the Special Issue Bioactive Compounds Derived from Marine Microalgae)
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Article
Biorefining and the Functional Properties of Proteins from Lipid and Pigment Extract Residue of Chlorella pyrenoidosa
Mar. Drugs 2019, 17(8), 454; https://doi.org/10.3390/md17080454 - 01 Aug 2019
Cited by 10 | Viewed by 2437
Abstract
Microalgae are considered as excellent candidates for bioactive compounds, yet microalgal residues remaining after the extraction of one or two compounds are usually discarded, which is not economical. This study demonstrates the alkaline extraction of proteins from Chlorella pyrenoidosa residue after lipid and [...] Read more.
Microalgae are considered as excellent candidates for bioactive compounds, yet microalgal residues remaining after the extraction of one or two compounds are usually discarded, which is not economical. This study demonstrates the alkaline extraction of proteins from Chlorella pyrenoidosa residue after lipid and pigment extractions, and their functional properties. Single-factor experiments and response surface methodology were used to obtain the optimal conditions for protein extraction. Based on our results, a maximum protein yield of 722.70 mg/g, was obtained under the following extraction conditions: sodium hydroxide concentration 7.90%, extraction temperature 70.00 °C, extraction time 34.80 min, and microalgal residue concentration 8.20 mg/mL. The molecular weight of microalgal residue protein isolate (MRPI) was mainly distributed at the regions of 0.18–0.50 kDa, 0.50–1.50 kDa, and 1.50–5.00 kDa. The essential amino acid content was greater than the values recommended by FAO/WHO standards; a high essential amino acid index value (1.49) was another good indication that MRPI is suitable for human consumption. Moreover, MRPI exhibited excellent emulsifying properties and antioxidant activity, which suggests it may be useful as an emulsifying agent and antioxidant. These findings could improve the extraction methods of functional protein from microalgal residue and add value to microalgae-based bioactive compound production processes. Full article
(This article belongs to the Special Issue Bioactive Compounds Derived from Marine Microalgae)
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Article
Spirulina Crude Protein Promotes the Migration and Proliferation in IEC-6 Cells by Activating EGFR/MAPK Signaling Pathway
Mar. Drugs 2019, 17(4), 205; https://doi.org/10.3390/md17040205 - 01 Apr 2019
Cited by 7 | Viewed by 2608
Abstract
Spirulina is a type of filamentous blue-green microalgae known to be rich in nutrients and to have pharmacological effects, but the effect of spirulina on the small intestine epithelium is not well understood. Therefore, this study aims to investigate the proliferative effects of [...] Read more.
Spirulina is a type of filamentous blue-green microalgae known to be rich in nutrients and to have pharmacological effects, but the effect of spirulina on the small intestine epithelium is not well understood. Therefore, this study aims to investigate the proliferative effects of spirulina crude protein (SPCP) on a rat intestinal epithelial cells IEC-6 to elucidate the mechanisms underlying its effect. First, the results of wound-healing and cell viability assays demonstrated that SPCP promoted migration and proliferation in a dose-dependent manner. Subsequently, when the mechanisms of migration and proliferation promotion by SPCP were confirmed, we found that the epidermal growth factor receptor (EGFR) and mitogen-activated protein (MAPK) signaling pathways were activated by phosphorylation. Cell cycle progression from G0/G1 to S phase was also promoted by SPCP through upregulation of the expression levels of cyclins and cyclin-dependent kinases (Cdks), which regulate cell cycle progression to the S phase. Meanwhile, the expression of cyclin-dependent kinase inhibitors (CKIs), such as p21 and p27, decreased with SPCP. In conclusion, our results indicate that activation of EGFR and its downstream signaling pathway by SPCP treatment regulates cell cycle progression. Therefore, these results contribute to the research on the molecular mechanism for SPCP promoting the migration and proliferation of rat intestinal epithelial cells. Full article
(This article belongs to the Special Issue Bioactive Compounds Derived from Marine Microalgae)
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Article
Eicosapentaenoic Acid Extraction from Nannochloropsis gaditana Using Carbon Dioxide at Supercritical Conditions
Mar. Drugs 2019, 17(2), 132; https://doi.org/10.3390/md17020132 - 22 Feb 2019
Cited by 29 | Viewed by 3646
Abstract
This research shows that carbon dioxide supercritical fluid (CO2-SF) is an emerging technology for the extraction of high interest compounds for applications in the manufacturing of pharmaceuticals, nutraceuticals, and cosmetics from microalgae. The purpose of this study is to recover fatty [...] Read more.
This research shows that carbon dioxide supercritical fluid (CO2-SF) is an emerging technology for the extraction of high interest compounds for applications in the manufacturing of pharmaceuticals, nutraceuticals, and cosmetics from microalgae. The purpose of this study is to recover fatty acids (FAs) and, more precisely, eicosapentaenoic acid (EPA) from Nannochloropsis gaditana biomass by CO2-SF extraction. In the paper, the effect of mechanical pre-treatment was evaluated with the aim of increasing FAs recovery. Extraction was performed at a pressure range of 250–550 bars and a CO2 flow rate of 7.24 and 14.48 g/min, while temperature was fixed at 50 or 65 °C. The effect of these parameters on the extraction yield was assessed at each extraction cycle, 20 min each, for a total extraction time of 100 min. Furthermore, the effect of biomass loading on EPA recovery was evaluated. The highest EPA extraction yield, i.e., 11.50 mg/g, corresponding to 27.4% EPA recovery, was obtained at 65 °C and 250 bars with a CO2 flow rate of 7.24 g/min and 1.0 g biomass loading. The increased CO2 flow rate from 7.24 to 14.48 g/min enhanced the cumulative EPA recovery at 250 bars. The purity of EPA could be improved by biomass loading of 2.01 g, even if recovery was reduced. Full article
(This article belongs to the Special Issue Bioactive Compounds Derived from Marine Microalgae)
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Article
Growth and Biochemical Composition of Porphyridium purpureum SCS-02 under Different Nitrogen Concentrations
Mar. Drugs 2019, 17(2), 124; https://doi.org/10.3390/md17020124 - 20 Feb 2019
Cited by 44 | Viewed by 3286
Abstract
Microalgae of the genus Porphyridium show great potential for large-scale commercial cultivation, as they accumulate large quantities of B-phycoerythrin (B-PE), long chain polyunsaturated fatty acids (LC-PUFAs) and exopolysaccharide (EPS). The present study aimed to adjust culture nitrogen concentrations to produce Porphyridium biomass rich [...] Read more.
Microalgae of the genus Porphyridium show great potential for large-scale commercial cultivation, as they accumulate large quantities of B-phycoerythrin (B-PE), long chain polyunsaturated fatty acids (LC-PUFAs) and exopolysaccharide (EPS). The present study aimed to adjust culture nitrogen concentrations to produce Porphyridium biomass rich in B-PE, LC-PUFAs and EPS. Porphyridium purpureum SCS-02 was cultured in ASW culture medium with low nitrogen supply (LN, 3.5 mM), medium nitrogen supply (MN, 5.9 mM) or high nitrogen supply (HN, 17.6 mM). HN significantly enhanced the accumulation of biomass, intracellular protein, B-PE and eicosapentaenoic acid. LN increased the intracellular carbohydrate and arachidonic acid content, and promoted the secretion of EPS. The total lipids content was almost unaffected by nitrogen concentration. Based on these results, a semi-continuous two-step process was proposed, which included the production of biomass rich in B-PE and LC-PUFAs with sufficient nitrogen, and induced EPS excretion with limited nitrogen and strong light. Full article
(This article belongs to the Special Issue Bioactive Compounds Derived from Marine Microalgae)
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Article
Immunostimulatory Phosphatidylmonogalactosyldiacylglycerols (PGDG) from the Marine Diatom Thalassiosira weissflogii: Inspiration for a Novel Synthetic Toll-Like Receptor 4 Agonist
Mar. Drugs 2019, 17(2), 103; https://doi.org/10.3390/md17020103 - 09 Feb 2019
Cited by 8 | Viewed by 2367
Abstract
An unprecedented phosphatidylmonogalactosyldiacylglycerol pool (PGDG, 1) rich in polyunsaturated fatty acids was isolated from the marine diatoms Thalassiosira weissflogii. Here we report for the first time the NMR characterization of this rare lipid from marine organisms along with a synthetic strategy [...] Read more.
An unprecedented phosphatidylmonogalactosyldiacylglycerol pool (PGDG, 1) rich in polyunsaturated fatty acids was isolated from the marine diatoms Thalassiosira weissflogii. Here we report for the first time the NMR characterization of this rare lipid from marine organisms along with a synthetic strategy for the preparation of a PGDG analog (2). PGDG 1 exhibited immunostimulatory activity in human dendritic cells (DCs) and the synthetic PGDG 2 was prepared to explore its mechanism of action. A Toll-like receptor-4 (TLR-4) agonistic activity was evidenced in human and murine DCs underlying the antigen-specific T-cell activation of this class of molecules. Full article
(This article belongs to the Special Issue Bioactive Compounds Derived from Marine Microalgae)
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Review

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Review
Potential Industrial Applications and Commercialization of Microalgae in the Functional Food and Feed Industries: A Short Review
Mar. Drugs 2019, 17(6), 312; https://doi.org/10.3390/md17060312 - 28 May 2019
Cited by 134 | Viewed by 10762
Abstract
Bioactive compounds, e.g., protein, polyunsaturated fatty acids, carotenoids, vitamins and minerals, found in commercial form of microalgal biomass (e.g., powder, flour, liquid, oil, tablet, or capsule forms) may play important roles in functional food (e.g., dairy products, desserts, pastas, oil-derivatives, or supplements) or [...] Read more.
Bioactive compounds, e.g., protein, polyunsaturated fatty acids, carotenoids, vitamins and minerals, found in commercial form of microalgal biomass (e.g., powder, flour, liquid, oil, tablet, or capsule forms) may play important roles in functional food (e.g., dairy products, desserts, pastas, oil-derivatives, or supplements) or feed (for cattle, poultry, shellfish, and fish) with favorable outcomes upon human health, including antioxidant, anti-inflammatory, antimicrobial, and antiviral effects, as well as prevention of gastric ulcers, constipation, anemia, diabetes, and hypertension. However, scale up remains a major challenge before commercial competitiveness is attained. Notwithstanding the odds, a few companies have already overcome market constraints, and are successfully selling extracts of microalgae as colorant, or supplement for food and feed industries. Strong scientific evidence of probiotic roles of microalgae in humans is still lacking, while scarce studies have concluded on probiotic activity in marine animals upon ingestion. Limitations in culture harvesting and shelf life extension have indeed constrained commercial viability. There are, however, scattered pieces of evidence that microalgae play prebiotic roles, owing to their richness in oligosaccharides—hardly fermented by other members of the intestinal microbiota, or digested throughout the gastrointestinal tract of humans/animals for that matter. However, consistent applications exist only in the dairy industry and aquaculture. Despite the underlying potential in formulation of functional food/feed, extensive research and development efforts are still required before microalgae at large become a commercial reality in food and feed formulation. Full article
(This article belongs to the Special Issue Bioactive Compounds Derived from Marine Microalgae)
Review
Microalgae for High-Value Products Towards Human Health and Nutrition
Mar. Drugs 2019, 17(5), 304; https://doi.org/10.3390/md17050304 - 24 May 2019
Cited by 212 | Viewed by 11779
Abstract
Microalgae represent a potential source of renewable nutrition and there is growing interest in algae-based dietary supplements in the form of whole biomass, e.g., Chlorella and Arthrospira, or purified extracts containing omega-3 fatty acids and carotenoids. The commercial production of bioactive compounds [...] Read more.
Microalgae represent a potential source of renewable nutrition and there is growing interest in algae-based dietary supplements in the form of whole biomass, e.g., Chlorella and Arthrospira, or purified extracts containing omega-3 fatty acids and carotenoids. The commercial production of bioactive compounds from microalgae is currently challenged by the biorefinery process. This review focuses on the biochemical composition of microalgae, the complexities of mass cultivation, as well as potential therapeutic applications. The advantages of open and closed growth systems are discussed, including common problems encountered with large-scale growth systems. Several methods are used for the purification and isolation of bioactive compounds, and many products from microalgae have shown potential as antioxidants and treatments for hypertension, among other health conditions. However, there are many unknown algal metabolites and potential impurities that could cause harm, so more research is needed to characterize strains of interest, improve overall operation, and generate safe, functional products. Full article
(This article belongs to the Special Issue Bioactive Compounds Derived from Marine Microalgae)
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