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Algae-Derived Bioactives: Key Molecular Interactions Govern High-Value Applications

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: 31 August 2026 | Viewed by 2551

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Special Issue Editors

Dr. Evan Stephens

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Guest Editor

School of Agriculture and Food Sustainability, The University of Queensland, Brisbane, QLD 4072, Australia
Interests: biotechnology; advanced nutrition science; research translation and commercialisation; bioeconomy and circular economy; sustainability sciences; AgTech
Special Issues, Collections and Topics in MDPI journals

Dr. Kirsten Heimann

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Guest Editor

Faculty of Science and Engineering, Southern Cross University, Lismore, NSW 2480, Australia
Interests: algal production; health and nutrition; biorefining of bioactive compounds; circular economy; environmental sustainability; soil and plant health product development
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The loss of arable land and effects of climate change challenge the sustainable agricultural production of agri-food for the rapidly growing human population. Balanced nutrition, however, plays a large role in the management of health and diseases. Based on the extent of global malnutrition provided by the World Health Organisation and the impact of climate change on agricultural production, traditional food production through agriculture and aquaculture alone is unlikely to be able to alleviate the increase in the global disease burden brought on or escalated by malnutrition. Algae, that is macro- and micro-algae, including cyanobacteria, are rich sources of essential nutrients, such as lipids, omega-3 fatty acids, protein, complex polysaccharides, antioxidants, vitamins, and minerals, yet global commercial algal production is still an emerging industry. This Special Issue aims to provide a fruitful synthesis of information on the key components of algal biomass, their molecular mode of action, the amounts required to alleviate nutritional shortcomings, and their market potential. This synthesis of information is targeted to be used by commercial producers and international research groups to harness the investment required for increasing global production volumes of algal species to supply the market with high-value bioactive products.

Malnutrition and inflammation are recognised as significantly contributing to the non-communicable chronic disease burden globally, affecting more than 2.5 billion people. Lifestyle choices and inadequate diets are recognised drivers for global declines in cardiovascular health, and inadequately formulated diets exacerbate proneness to muscle and weight loss, escalate the progression of physical and mental dysfunction, and negatively affect the quality of life and clinical outcomes of older people. Considering the growing human population, climate change, and loss of arable land, a key question is how can diets be fortified economically and sustainably with essential nutrients to kerb the impact malnutrition has on the global disease burden?

Many algae species are rich in nutrients such as lipids and omega-3 fatty acids, protein, beneficial complex polysaccharides, and other health-promoting bioactives, minerals, vitamins, and antioxidants and have been used in Asian diets for thousands of years. The health benefits of many algal bioactive molecules have also been recognised. Despite this, the general inclusion of algae or algae-derived molecules is currently not realised due to knowledge gaps concerning dietary guidelines, the underpinning molecular mechanisms of algal bioactive compounds in health and disease management, and the comparatively low volumes produced commercially. Specifically, this Special Issue aims to elucidate the molecular interactions that govern the efficacy of vast and diverse algae-derived bioactive molecules in the management of health and disease. Thus, this Special Issue aims to provide a molecular foundation for the health benefit claims of key components of algal biomass through the elucidation of their molecular interactions. This information will in turn be used to analyse market potential. This comprehensive algal species-integrated information will aid the global expansion of algal production through the manufacturing of high-value products and applications.

Dr. Evan Stephens
Dr. Kirsten Heimann
Guest Editors

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Keywords

microalgae
macroalgae
cyanobacteria
bioactive compounds
health and nutrition
algal food products
market analysis

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Published Papers (4 papers)

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Research

27 pages, 7255 KB

Open AccessArticle

Cytotoxic and Immunomodulatory Effects of Phormidesmis molle Extract on Human Cells In Vitro

by Ivanka Teneva, Krum Bardarov, Tsvetelina Batsalova, Dzhemal Moten and Balik Dzhambazov

Int. J. Mol. Sci. 2026, 27(5), 2236; https://doi.org/10.3390/ijms27052236 - 27 Feb 2026

Viewed by 423

Abstract

Cyanobacteria of the genus Phormidesmis are recognized as a promising source of biologically active secondary metabolites with anticancer and immunomodulatory properties. In the present study, we investigated both the cytotoxic and immunological effects of an extract obtained from Phormidesmis molle PACC (Plovdiv Algal Culture Collection) 8140 as well as its chemical composition. The extract was profiled by LC-ESI-MS/MS (Liquid chromatography—electrospray ionization—tandem mass spectrometry), and selected compounds were evaluated with in silico ADMET (Absorption, distribution, metabolism, excretion and toxicity) modeling. The cytotoxic potential of the extract was evaluated in vitro using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay on human colorectal adenocarcinoma cell lines (Caco-2, HT-29, and LS-180). The immunological impact of the extract was assessed on human peripheral blood mononuclear cells (PBMCs) isolated from healthy donors. PBMCs were treated with 100 µg/mL extract for 48 h, followed by flow cytometric immunophenotyping and ELISA (Enzyme-linked immunosorbent assay)-based cytokine quantification. The extract induced a concentration- and time-dependent decrease in cancer cell viability after 24, 48, and 72 h of exposure. At 72 h, treatment with the highest concentration (200 µg/mL) reduced cell viability to 74% in Caco-2 cells, 69–70% in HT-29 cells, and 59–61% in LS-180 cells. Morphological changes observed after treatment with Phormidesmis extract showed pronounced cytotoxic and apoptosis-related effects in the colorectal cancer cell lines tested. Immunophenotyping revealed a pronounced expansion of natural killer (NK) cells (CD56⁺ and/or CD16⁺). CD3⁻CD56⁻CD16⁺ NK population was markedly increased (from 67.7 ± 0.95% in non-treated PBMCs to 94.66 ± 0.90% in extract-treated PBMCs, p < 0.001). In contrast, the proportions of CD8⁺ T cells, CD19⁺ B cells, and CD11b⁺ monocytes were significantly reduced (from 21.5 ± 4.50% to 7.22 ± 0.41%, from 11.9 ± 1.70% to 6.06 ± 0.42%, and from 66.4 ± 0.60% to 34.4 ± 0.87%, respectively). Cytokine analysis demonstrated strong suppression of Th1-associated cytokines, with significantly reduced interferon gamma (IFN-γ, 461 ng/mL in controls vs. 84 ng/mL in extract-treated cultures) and tumor necrosis factor alpha (TNF-α) levels (169 ng/mL in controls vs. 32 ng/mL in extract-treated cultures), whereas nterleukin-6 (IL-6) was moderately elevated (from 158 ng/mL in controls to 234 ng/mL in extract-treated cultures) and IL-10 remained low. These findings demonstrate that P. molle extract combines cytotoxic activity against cancer cells with potent immunomodulatory effects, highlighting its potential as a source of bioactive compounds for immune-based therapeutic strategies. Full article

(This article belongs to the Special Issue Algae-Derived Bioactives: Key Molecular Interactions Govern High-Value Applications)

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21 pages, 4297 KB

Open AccessArticle

Changes in Metabolism and Lipid Composition with Nitrogen Starvation and Recovery in a New Productive Strain of Neochlorella semenenkoi Using N¹⁵-Isotopic Labeling and HRMS

by Anna Vishnevskaya, Anton Bashilov, Dmitry Senko, Sergey Osipenko, Maria Sinetova, Nikita Malyshev, Philipp Khaitovich, Eugene Nikolaev and Yury Kostyukevich

Int. J. Mol. Sci. 2026, 27(5), 2128; https://doi.org/10.3390/ijms27052128 - 25 Feb 2026

Viewed by 418

Abstract

Microscopic green algae are active producers of beneficial compounds, particularly those containing nitrogen. However, the metabolism of nitrogen-containing compounds is diverse and depends on the conditions of the nitrogen source. As a result, the approach to studying the metabolism of nitrogen-containing compounds becomes more complicated. This work demonstrates the metabolic changes in the high-productive green algae Neochlorella semenenkoi IPPAS C-1210 under conditions of nitrogen starvation and subsequent reintake, using high-performance liquid chromatography–mass spectrometry (HPLC–MS) with ¹⁵N isotopic labeling. The presented results include semi-quantitative chromatography–mass spectrometric analysis for 17 amino acids, a metabolomic profile of over 40 isotopically labeled compounds, an assessment of metabolic flux via isotopic incorporation, and an analysis of cellular lipid composition under varying growth conditions. The findings indicate that this strain can utilize ammonium acetate as a nitrogen source, consuming nitrogen in the ammonium form. The degree of isotopic labeling in compounds often diverged significantly from their quantitative changes (concentrations and chromatographic peak areas), suggesting that isotopic analysis may offer advantages over purely quantitative analysis for biological systems. Furthermore, in vivo biological isotopic labeling is shown to assist in identifying compounds absent from standard mass spectrometric databases. Full article

(This article belongs to the Special Issue Algae-Derived Bioactives: Key Molecular Interactions Govern High-Value Applications)

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18 pages, 1656 KB

Open AccessArticle

Arthrospira platensis Preserves Uterine Function by Modulating Electromechanical Coupling and Redox Pathways During Resistance Training in Female Rats

by Bárbara Cavalcanti Barros, Anderson Fellyp Avelino Diniz, Francisco Fernandes Lacerda-Júnior, Petruska Pessoa da Silva Souza, Adriano Francisco Alves, Paula Benvindo Ferreira, Fabiana de Andrade Cavalcante and Bagnólia Araújo da Silva

Int. J. Mol. Sci. 2025, 26(23), 11440; https://doi.org/10.3390/ijms262311440 - 26 Nov 2025

Cited by 1 | Viewed by 503

Abstract

Algae-derived bioactives have emerged as promising nutraceuticals due to their ability to modulate key molecular pathways under physiological stress. Arthrospira platensis (Spirulina), a cyanobacterium widely recognized for its antioxidant and anti-inflammatory properties, is proposed as a functional supplement to preserve smooth muscle physiology. Progressive strength training (PST) can induce oxidative stress and disrupt electromechanical coupling in the uterus, potentially impairing female reproductive function. This study investigated whether supplementation with A. platensis prevents PST-induced uterine dysfunction and elucidated the molecular mechanisms involved. Virgin Wistar rats were divided into five groups: sedentary with saline (GS), sedentary with A. platensis (GAP100), adapted control (GC), PST-trained (GT), and PST-trained with A. platensis (GTAP100). An eight-week water-jump PST protocol was applied. Uterine contractile responses were recorded in isolated organ baths after cumulative KCl stimulation, in the absence or presence of pathway-specific inhibitors targeting nitric oxide synthase, cyclooxygenase, NADPH oxidase, or superoxide dismutase. Histological evaluations of uterine and ovarian tissues were also performed. PST increased contractile efficacy and myometrial thickness, associated with oxidative stress and activation of NO, COX, and NADPH oxidase pathways. Supplementation with A. platensis attenuated these alterations by enhancing NO signaling, stimulating relaxant prostanoids, and reducing superoxide production. These protective effects were abolished by inhibitors, confirming mechanistic involvement. Overall, our findings provide molecular evidence that A. platensis supplementation preserves uterine smooth muscle physiology under high-intensity resistance training, supporting its potential as a nutraceutical strategy for female reproductive health. Full article

(This article belongs to the Special Issue Algae-Derived Bioactives: Key Molecular Interactions Govern High-Value Applications)

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16 pages, 2035 KB

Open AccessArticle

Algae-Derived C-Phycocyanin Mitigates AGE–RAGE-Induced ER Stress and Mitochondrial Apoptosis: Implications for Diabetes-Associated Neurodegeneration

by Mei Chou Lai, Wayne Young Liu, Yu-Cheng Tzeng and I-Min Liu

Int. J. Mol. Sci. 2025, 26(22), 11077; https://doi.org/10.3390/ijms262211077 - 16 Nov 2025

Cited by 3 | Viewed by 751

Abstract

Impaired glucose metabolism elevates the risk of neurodegenerative diseases by activating the receptor for advanced glycation end products (RAGE), thereby promoting oxidative and endoplasmic reticulum (ER) stress that leads to neuronal apoptosis. C-phycocyanin (C-PC), a natural pigment–protein complex derived from algae, possesses potent antioxidant and antiglycation properties; however, its capacity to modulate RAGE-mediated neurotoxicity remains to be fully elucidated. In this study, we established a RAGE-driven neuronal injury model by exposing differentiated SH-SY5Y cells to advanced glycation end products (AGEs; 300 μg/mL). Pretreatment with C-PC (15–50 μmol/L) improved cell viability, preserved neuronal morphology, and attenuated AGEs-induced oxidative stress, as indicated by reduced intracellular reactive oxygen species and mitochondrial superoxide levels. Furthermore, C-PC inhibited activation of the PERK-CHOP pathway, and upregulated Bcl-2 while downregulating Bax, thereby preventing cytochrome c release and reducing caspase-9/3 activation as well as apoptotic DNA fragmentation. These neuroprotective effects of C-PC were comparable to those observed with the selective RAGE antagonist FPS-ZM1. In conclusion, our findings demonstrate that C-PC confers robust protection against AGEs-induced neuronal injury by suppressing oxidative and ER stress pathways downstream of RAGE activation, highlighting its potential as a natural modulator of the AGE–RAGE axis for the prevention or treatment of diabetes-associated neurodegeneration. Full article

(This article belongs to the Special Issue Algae-Derived Bioactives: Key Molecular Interactions Govern High-Value Applications)

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