Marine Drugs

22 pages, 3116 KB

Open AccessArticle

Preparation of a Thermosensitive Chitosan–Sea Cucumber Peptide Hydrogel and Its Alleviating Effect on Acute Alcohol-Induced Dual Liver and Brain Injury in Mice

by Jiaqi Guo, Songzhi Kong, Chen Chen, Guiping Lu, Zirui Li, Jinhui Chen and Meiyin Liang

Mar. Drugs 2026, 24(9), 294; https://doi.org/10.3390/md24090294 (registering DOI) - 23 Aug 2026

Abstract

Excessive short-term ethanol intake often causes acute intoxication and multi-organ damage, especially to the liver and brain. Thus, developing safe and effective preparations for hangover relief, liver protection, and brain function regulation is of great practical significance. In this study, we fabricated a [...] Read more.

Excessive short-term ethanol intake often causes acute intoxication and multi-organ damage, especially to the liver and brain. Thus, developing safe and effective preparations for hangover relief, liver protection, and brain function regulation is of great practical significance. In this study, we fabricated a thermosensitive chitosan (CS)–sea cucumber peptide (SCP) hydrogel (CS–SCP gel) loaded with SCP using NaHCO₃ as a crosslinker and characterized its properties. Kunming mouse models of anti-intoxication and acute alcohol-induced liver and brain injuries were established. The anti-intoxication and organ-protective effects of the CS–SCP gel were comprehensively evaluated through behavioral observation, liver histopathology, and biochemical assays of serum and liver, kidney, and brain tissues. The CS–SCP gel exhibited a phase transition temperature of 35.7 °C, a water absorption rate of 1015.47%, and a cumulative peptide release of 74.83% within 330 min. In mice, it prolonged the latency to drunkenness; shortened alcohol-induced sleep and sobering time; reduced blood ethanol, transaminase, and lipid levels; upregulated hepatic antioxidant enzymes; downregulated pro-inflammatory cytokines, and alleviated lipid peroxidation. It also enhanced brain antioxidant capacity, suppressed cerebral inflammatory cytokines, and maintained cholinergic neurotransmitter homeostasis. Collectively, with sustained release, CS–SCP gel is expected to prolong the pharmacological action of SCP, enhance therapeutic efficacy, and protect against alcohol-induced liver and brain injury through the regulation of oxidative stress and attenuation of inflammation. Full article

(This article belongs to the Special Issue Marine-Derived Bioactive Compounds and Materials for Advanced Biomaterials Development)

24 pages, 11375 KB

Open AccessArticle

Stigmasterol-Stabilized Nanoliposomes Enhance Oral Delivery of Collagen Peptides Through Improved Systemic Exposure of Hydroxyproline-Containing Peptides

by Zifang Zhao, Wenshuo Xing, Meichao Zhang, Chengsuo Liu, Weijie Zhang, Haohao Wu and Changhu Xue

Mar. Drugs 2026, 24(8), 293; https://doi.org/10.3390/md24080293 - 21 Aug 2026

Abstract

Collagen peptides (CPs) possess diverse biological activities, yet their oral efficacy is limited by gastrointestinal degradation and restricted systemic exposure of intact bioactive peptide species. Herein, a stable cholesterol-free nanoliposome system was developed using soybean phospholipids and stigmasterol through high-pressure microfluidization, followed by [...] Read more.

Collagen peptides (CPs) possess diverse biological activities, yet their oral efficacy is limited by gastrointestinal degradation and restricted systemic exposure of intact bioactive peptide species. Herein, a stable cholesterol-free nanoliposome system was developed using soybean phospholipids and stigmasterol through high-pressure microfluidization, followed by tangential flow filtration and spray drying to obtain a stable dry formulation. The optimized nanoliposomes exhibited a particle size below 100 nm, high peptide loading, excellent redispersibility, and remarkable physicochemical stability during refrigerated storage and under different pH and thermal conditions. During simulated gastrointestinal digestion, the stigmasterol-stabilized phospholipid bilayer effectively preserved encapsulated CPs throughout the gastric phase while facilitating peptide release under intestinal conditions. Oral administration in rats significantly enhanced collagen peptide bioavailability, increasing the plasma exposure (iAUC_{0–8 h}) of total hydroxyproline by 3.84-fold compared with free CPs. Peptide-bound hydroxyproline exposure increased 9.3-fold and accounted for approximately 94% of total absorbed hydroxyproline. UHPLC–HRMS analysis confirmed substantially enhanced systemic exposure of multiple characteristic hydroxyproline-containing dipeptides and tripeptides following nanoliposomal delivery. These findings indicate that stigmasterol-containing nanoliposomes improve the gastrointestinal stability and systemic delivery performance of collagen peptides, providing a promising strategy for enhancing the oral delivery potential of food-derived bioactive peptides. Full article

(This article belongs to the Special Issue Research on Marine-Derived Functional Foods)

► Show Figures

Graphical abstract

18 pages, 3557 KB

Open AccessArticle

Sequential Production of Sodium Alginate and Biomethane from Holopelagic Sargassum spp. to Promote a Circular Economy in the Mexican Caribbean

by Karla J. Azcorra-May, Elda I. España-Gamboa, Liliana Alzate-Gaviria, Jorge A. Domínguez-Maldonado, Tanit Toledano-Thompson, Rosa M. Leal-Bautista, José M. Cervantes-Uc and Raúl Tapia-Tussell

Mar. Drugs 2026, 24(8), 292; https://doi.org/10.3390/md24080292 - 21 Aug 2026

Abstract

This research proposes an approach based on a circular economy principle for the integral valorization of Sargassum from the Mexican Caribbean. The biomass was characterized through proximal and elemental analyses, and then an oxidative pretreatment was carried out to enhance a sequential processing [...] Read more.

This research proposes an approach based on a circular economy principle for the integral valorization of Sargassum from the Mexican Caribbean. The biomass was characterized through proximal and elemental analyses, and then an oxidative pretreatment was carried out to enhance a sequential processing scheme to extract sodium alginate and use the solid waste as a substrate for biogas production via anaerobic digestion. The oxidative pretreatment successfully reduces the recalcitrant content and the concentration of heavy metals. The sodium alginate extracted from treated biomass achieves a yield higher than 20%; the characterization of the polymer via nuclear magnetic resonance showed that the mannuronic-to-guluronic ratio was between 0.34 and 0.62, indicating the potential for its use for environmental and biomedical applications. The highest yield in methane production was 328 mL CH₄/g of volatile solids, with a purity of 90%, and was achieved using the waste from alginate extraction with an inoculum-to-substrate ratio of 1:1. The experimental data presented an excellent fit to a Gompertz model (R² > 0.99). The proposed valorization pathway improves the sustainability of Sargassum management, prioritizing the recovery of high-value compounds before energy production. This circular approach provides a framework for converting environmental challenges into opportunities in the Caribbean. Full article

(This article belongs to the Special Issue Sustainable Extraction and Valorization of Marine Bioactive Compounds)

► Show Figures

Graphical abstract

25 pages, 2197 KB

Open AccessReview

Marine-Derived Natural Products Against Flaviviruses: Mechanisms, Evidence, and Future Directions

by Hyeon Seung Park, Min Seo Heo, Hyuk Nam Kwon, Yo Han Jang, Munhyung Bae and Yun Kwon

Mar. Drugs 2026, 24(8), 291; https://doi.org/10.3390/md24080291 - 21 Aug 2026

Abstract

Although flaviviruses, including DENV, ZIKV and JEV, remain important causes of febrile, congenital, and neurological diseases, treatment options remain largely supportive, with limited availability of virus-specific antiviral therapies. Marine organisms and marine-derived microorganisms produce chemically distinct antiviral materials, including sulfated polysaccharides, terpenoids, alkaloids, [...] Read more.

Although flaviviruses, including DENV, ZIKV and JEV, remain important causes of febrile, congenital, and neurological diseases, treatment options remain largely supportive, with limited availability of virus-specific antiviral therapies. Marine organisms and marine-derived microorganisms produce chemically distinct antiviral materials, including sulfated polysaccharides, terpenoids, alkaloids, peptides, cyclodepsipeptides, and polyketides. However, their activities range from preliminary extract-level inhibition to direct biochemical target validation, making mechanistic comparison difficult. This review critically evaluates marine-derived anti-flaviviral agents using two complementary dimensions, the infection stage implicated by experimental assays and the strength of evidence supporting that assignment. DENV evidence is dominated by sulfated algal macromolecules that interfere with adsorption or internalization, whereas ZIKV studies encompass lipophilic algal metabolites, fungal alkaloids, cyclodepsipeptides, and a few target-oriented candidates. Across the field, most reports remain stage-associated rather than target-validated. Cross-study potency comparisons are constrained by differences in virus strains, cell models, assay formats, and treatment schedules. JEV-specific evidence is particularly sparse. Based on the DENV and ZIKV evidence map, we propose concise priorities for JEV-oriented discovery: early compound-level dereplication, parallel cytotoxicity testing, orthogonal confirmation of productive infection, stage-resolved assays, and biochemical or genetic validation of conserved flaviviral targets. This evidence-based framework can help distinguish promising chemical candidate scaffolds from preliminary antiviral signals and guide mechanism-informed development of marine-derived natural products against flaviviruses. Full article

(This article belongs to the Section Marine Pharmacology)

► Show Figures

Figure 1

21 pages, 6475 KB

Open AccessArticle

Structural Characterization and Biological Evaluation of a Novel GlcNAc-Bearing Exopolysaccharide from the Mangrove Endophytic Fungus Penicillium janthinellum N29

by Zhuling Shao, Luya Wang and Xin Wang

Mar. Drugs 2026, 24(8), 290; https://doi.org/10.3390/md24080290 - 21 Aug 2026

Abstract

A novel, uniform acid heteropolysaccharide with a molecular weight of 13.14 kDa was isolated from the fermented broth of the mangrove endophytic fungus Penicillium janthinellum N29, designated as PJ3-1. A structural analysis showed that PJ3-1 is a straight-chain heteropolysaccharide containing GlcN, GlcNAc, Glc [...] Read more.

A novel, uniform acid heteropolysaccharide with a molecular weight of 13.14 kDa was isolated from the fermented broth of the mangrove endophytic fungus Penicillium janthinellum N29, designated as PJ3-1. A structural analysis showed that PJ3-1 is a straight-chain heteropolysaccharide containing GlcN, GlcNAc, Glc and GlcA in the ratio of 12.23:1.79:10.93:1.00. PJ3-1 markedly inhibits α-glucosidase activity and relieves insulin resistance in HepG2 cells. It alleviates lipid peroxidation and upregulates the activities of endogenous antioxidant enzymes. In addition, it also significantly scavenges hydroxyl radicals, ferrous ions, superoxide anions, DPPH radicals and ABTS radicals and enhances reducing power in a dose-dependent manner. Collectively, these findings suggest that PJ3-1 has the potential to serve as a natural antioxidant and hypoglycemic agent for functional food or pharmaceutical applications. Full article

(This article belongs to the Special Issue Diversity of Marine Fungi as a Source of Bioactive Natural Products, 3rd Edition)

► Show Figures

Graphical abstract

24 pages, 9722 KB

Open AccessArticle

Cytotoxic Potential of Marine-Derived Fungi Isolated from Sponges and Brown Algae of Mauritius

by Jessica Mélanie Wong Chin, Annaelle Hip Kam, Rajesh Jeewon, Abdulwahed Fahad Alrefaei, Teeshan Bahorun, Daneshwar Puchooa, Neil O. Carragher and Vidushi S. Neergheen

Mar. Drugs 2026, 24(8), 289; https://doi.org/10.3390/md24080289 - 21 Aug 2026

Abstract

Marine fungi associated with sponges and brown algae are promising sources of pharmacologically active compounds. This study investigated the cytotoxic potential and metabolomic profiles of fungal strains isolated from the marine environment of Mauritius. Among the twenty extracts screened, the mycelium extracts were [...] Read more.

Marine fungi associated with sponges and brown algae are promising sources of pharmacologically active compounds. This study investigated the cytotoxic potential and metabolomic profiles of fungal strains isolated from the marine environment of Mauritius. Among the twenty extracts screened, the mycelium extracts were more cytotoxic than the broth extracts. Four extracts demonstrated the most potent activity: Aspergillus chevalieri (F2M), Aspergillus ochraceus (F25M) and Biatriospora sp. (F34M, F34B). The algal endophyte Aspergillus chevalieri (F2M) mycelium extract displayed an IC₅₀ of 14.27 ± 1.22 µg/mL after 24 h against HepG2 cells. The sponge-associated fungi Aspergillus ochraceus (F25M) showed promising cytotoxic activities against HepG2 cells (IC₅₀ of 8.775 ± 0.78 µg/mL) after 24 h of treatment, with a selectivity index of 2.27, and had the lowest IC₅₀ (2.49 ± 0.60 µg/mL after 24 h; 7.14 ± 3.14 µg/mL after 48 h) against FLO-1 cells, also reducing tumor spheroid growth and integrity during the first four hours. All four extracts increased the intracellular ROS production, but only the mycelium extract of A. chevalieri (F2M) significantly increased superoxide dismutase (SOD) and catalase (CAT) activity. Metabolomic profiling identified diverse compound classes, including alkaloids, terpenoids, amino acids, anthraquinones and coumarins. The findings revealed that the marine fungi from Mauritius are promising sources of cytotoxic metabolites that require purification and subsequent confirmation and mechanistic studies. Full article

(This article belongs to the Special Issue Chemical Diversity and Therapeutic Potentials of Marine Invertebrates)

► Show Figures

Graphical abstract

44 pages, 13088 KB

Open AccessReview

Antioxidant Compounds in Microalgae and Cyanobacteria: A Sustainable Source of Bioactive Molecules

by Patricia Gómez-Villegas, Encarnación Díaz-Santos, Rocío Rengel, Ana Molina-Márquez, José María Rodríguez-González, Javier Vigara, Rosa León and Antonio Leon-Vaz

Mar. Drugs 2026, 24(8), 288; https://doi.org/10.3390/md24080288 - 21 Aug 2026

Abstract

The search for antioxidant compounds from aquatic or marine environments to cope with the harmful effects of reactive oxygen species (ROS) is one of the major challenges in contemporary blue biotechnology. Among marine microorganisms, microalgae have emerged as promising candidates for the discovery [...] Read more.

The search for antioxidant compounds from aquatic or marine environments to cope with the harmful effects of reactive oxygen species (ROS) is one of the major challenges in contemporary blue biotechnology. Among marine microorganisms, microalgae have emerged as promising candidates for the discovery and production of natural bioactive molecules with antioxidant properties. This review highlights the potential of microalgae and cyanobacteria as a sustainable source of antioxidant compounds and examines their growing relevance in biotechnology and pharmaceutical applications. A broad range of antioxidant metabolites produced by microalgae, including carotenoids, fatty acids, vitamins, polyphenols, and flavonoids, has also been discussed, with particular emphasis on their antioxidant mechanisms and bioactive properties. This review also integrates antioxidant mechanisms with the physiological and metabolic responses, underlying antioxidant production and sustainable strategies used to enhance their accumulation. Furthermore, microalgae offer the advantage of sustainable production systems, with the potential to enhance the biosynthesis and accumulation of valuable compounds through optimized cultivation strategies. Thus, different sustainable approaches aimed at increasing antioxidant compound production or reducing operational costs in microalgae cultivation are discussed to identify efficient and economically viable processes that maximize the biotechnological potential of these microorganisms for future industrial applications. Full article

(This article belongs to the Special Issue Algae Research: From Cultivation to Drugs)

► Show Figures

Figure 1

26 pages, 5121 KB

Open AccessReview

Advances in Carrageenases: Molecular Engineering, Immobilization Techniques, and Biomedical Potential of Carrageenan Oligosaccharides

by Qiangzhuang Xie, Jiahong Lan, Yanhong Chen, Zhipeng Li, Lijun Li, Zedong Jiang, Hui Ni and Yanbing Zhu

Mar. Drugs 2026, 24(8), 287; https://doi.org/10.3390/md24080287 - 21 Aug 2026

Abstract

Carrageenan is a sulfated polysaccharide extracted from red algae, widely utilized in the food and pharmaceutical industries due to its unique gelling properties and biological activities. However, its high molecular weight and low solubility limit certain high-value applications. Carrageenases specifically degrade carrageenan to [...] Read more.

Carrageenan is a sulfated polysaccharide extracted from red algae, widely utilized in the food and pharmaceutical industries due to its unique gelling properties and biological activities. However, its high molecular weight and low solubility limit certain high-value applications. Carrageenases specifically degrade carrageenan to produce low-molecular-weight oligosaccharides with excellent bioactivities, thereby overcoming this bottleneck. This review systematically summarizes the microbial sources of carrageenases and the classification characteristics of their three types (κ, ι, and λ) within the GH16, GH82, and GH150 families. Furthermore, it highlights recent advances in molecular engineering strategies, including site-directed mutagenesis and non-catalytic domain fusion, as well as enzyme immobilization techniques utilizing carriers such as magnetic nanoparticles and metal–organic frameworks, which significantly enhance thermostability, catalytic efficiency, and reusability. Additionally, the potential applications of carrageenan oligosaccharides in biomedical fields, including antioxidant, immunomodulatory, antitumor, and anti-inflammatory activities, are thoroughly discussed. This review provides a theoretical reference for the rational design and industrial application of carrageenases, while also offering new insights for the high-value development of algal resources. Full article

(This article belongs to the Special Issue Marine Carrageenan—from Sustainable Extraction to High-Value Innovation)

► Show Figures

Figure 1

37 pages, 4249 KB

Open AccessReview

Marine Food Polysaccharides: Representative Structural Features, Immunomodulatory Effects, and Food Applications

by Yunhan Li, Xinhong Wang, Xiang Li, Nan Wei, Dawei Jiang, Ming Li, Chong Yu, Juan Guo, Keqiang Li, Haifeng Wang and Ning Li

Mar. Drugs 2026, 24(8), 286; https://doi.org/10.3390/md24080286 - 20 Aug 2026

Abstract

Marine food polysaccharides (MFPs) are structurally diverse biopolymers shaped by the marine environment, with emerging roles in immune regulation and food design. This review summarizes the representative structural features of MFPs, and evaluates their effects on innate and adaptive immune responses and associated [...] Read more.

Marine food polysaccharides (MFPs) are structurally diverse biopolymers shaped by the marine environment, with emerging roles in immune regulation and food design. This review summarizes the representative structural features of MFPs, and evaluates their effects on innate and adaptive immune responses and associated signaling pathways. The influences of molecular weight, sulfation, branching, and monosaccharide composition on biological activity are also discussed. In addition, this review discusses the applications of MFPs in food additives, packaging, delivery systems, and functional foods. Despite growing evidence, challenges remain in resolving higher-order structures, understanding bidirectional immune effects and maintaining stability in complex matrices. Advancing integrated structural and food design approaches could enable the rational use of MFPs as next-generation functional ingredients. Full article

(This article belongs to the Special Issue Advances in Marine Polysaccharides: From Structure and Function to Biomedical and Nutraceutical Applications)

► Show Figures

Figure 1

29 pages, 6235 KB

Open AccessArticle

Synergistic Application of Cytidine Monophosphate and Sodium Chloride for Enhanced Co-Production of Astaxanthin and Fatty Acids in Haematococcus lacustris Motile Cells Under High-Light Stress

by Xiaoyuan Su, Hailiang Xing, Kai Liu, Ya Zhao, Lijin Dong, Ziyan Zhou, Na Zhou, Xue Sun, Liuquan Zhang, Nianjun Xu and Chaoyang Hu

Mar. Drugs 2026, 24(8), 285; https://doi.org/10.3390/md24080285 - 19 Aug 2026

Abstract

This study evaluated the synergistic effects of sodium chloride (NaCl) and cytidine monophosphate (CMP) on enhancing the co-production of astaxanthin and fatty acids while suppressing secondary cell wall (SCW) formation in Haematococcus lacustris (synonym: H. pluvialis) under high-light stress. An orthogonal design [...] Read more.

This study evaluated the synergistic effects of sodium chloride (NaCl) and cytidine monophosphate (CMP) on enhancing the co-production of astaxanthin and fatty acids while suppressing secondary cell wall (SCW) formation in Haematococcus lacustris (synonym: H. pluvialis) under high-light stress. An orthogonal design identified the optimal combination (0.5 g/L NaCl and 0.5 mM CMP), which significantly increased astaxanthin yield by over 35.6% and total fatty acid yield by 28%, while maintaining 96.8% of cells in motile state (SCW-deficient). Physiological analyses revealed elevated reactive oxygen species levels, concomitant with higher actual photochemical efficiency (Fv′/Fm′) and relative electron transport rates II (rETR(II)) along with enhanced non-photochemical quenching (NPQ) capacity, and metabolic reprogramming characterized by the accumulation of lipids, sugars, and starch alongside decreased protein yield. Metabolomics indicated reduced carbon supply for SCW polysaccharide biosynthesis, coupled with decreased protein yield and altered amino acid profiles characteristic of nitrogen-limited metabolism, which collectively favored the reallocation of carbon resources toward nitrogen-free high-value products. Transcriptomics confirmed the downregulation of SCW component biosynthetic genes and the upregulation of the methylerythritol phosphate (MEP) pathway and astaxanthin biosynthetic pathway. Scale-up experiments validated this strategy for producing astaxanthin-rich motile cells, offering a promising approach for microalgal biorefinery. Full article

(This article belongs to the Section Marine Biotechnology Related to Drug Discovery or Production)

► Show Figures

Graphical abstract

27 pages, 2051 KB

Open AccessReview

Marine-Derived Rare Actinomycetes: Metabolites and Their Biosynthesis

by Juwan Son, Hyeon Seung Park, Sang Heon Jung, Min Seo Heo, Yun Kwon and Munhyung Bae

Mar. Drugs 2026, 24(8), 284; https://doi.org/10.3390/md24080284 - 19 Aug 2026

Abstract

Marine-derived rare actinomycetes are a chemically prolific yet underexploited source of structurally diverse secondary metabolites. In this review, rare actinomycetes are operationally defined as marine-derived non-Streptomyces actinomycetes that remain comparatively underexplored yet possess demonstrated or predicted capacity for specialized-metabolite biosynthesis. Genome sequencing [...] Read more.

Marine-derived rare actinomycetes are a chemically prolific yet underexploited source of structurally diverse secondary metabolites. In this review, rare actinomycetes are operationally defined as marine-derived non-Streptomyces actinomycetes that remain comparatively underexplored yet possess demonstrated or predicted capacity for specialized-metabolite biosynthesis. Genome sequencing has revealed that their biosynthetic potential greatly exceeds the range of metabolites recovered under standard cultivation conditions. However, many reported compounds remain only loosely associated with the gene clusters that encode them. This review provides a biosynthesis-centered perspective on marine-derived rare actinomycetes, focusing on secondary metabolites for which biosynthetic gene clusters (BGCs) or pathways have been proposed, experimentally assessed, or functionally validated. It focuses on compounds reported after 2017, along with earlier metabolites whose biosynthetic origins were resolved only later. Representative examples are organized by genus and structural class and weighed according to the level of evidence linking each metabolite to its BGC, ranging from bioinformatic prediction and metabolomic correlation to validation by gene inactivation, heterologous expression, and enzymatic characterization. The surveyed metabolites include polyketides, nonribosomal peptides, polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) hybrids, siderophores, angucyclines, anthracyclines, macrolides, diketopiperazine derivatives, and other unusual scaffolds. Collectively, these findings indicate how integrating genome mining, metabolomics, and molecular networking with targeted biosynthetic experiments can accelerate marine natural product discovery and unravel novel enzymatic functions and biosynthetic mechanisms in rare actinomycetes. Full article

(This article belongs to the Special Issue Natural Products from Marine Streptomyces)

► Show Figures

Graphical abstract

20 pages, 5155 KB

Open AccessArticle

Concentration-Dependent Effects of Salicylic Acid and Methyl Salicylate on Chlorophylls, Carotenoids, Fatty Acids, and Phenolic Compounds in the Green Microalga Planktochlorella nurekis

by Jan Cichoński, Patrycja Michalik, Wiktor Nowak, Paweł Czerniewicz, Ewelina Kuna, Magdalena Słowik-Borowiec and Grzegorz Chrzanowski

Mar. Drugs 2026, 24(8), 283; https://doi.org/10.3390/md24080283 - 17 Aug 2026

Abstract

Microalgae are a rich source of bioactive metabolites, including unsaturated fatty acids, chlorophylls, carotenoids, and phenolic compounds with antioxidant and nutraceutical potential. Salicylic acid (SA) and its volatile ester, methyl salicylate (MS), are well-known elicitors of secondary metabolism in higher plants, yet their [...] Read more.

Microalgae are a rich source of bioactive metabolites, including unsaturated fatty acids, chlorophylls, carotenoids, and phenolic compounds with antioxidant and nutraceutical potential. Salicylic acid (SA) and its volatile ester, methyl salicylate (MS), are well-known elicitors of secondary metabolism in higher plants, yet their mechanisms of action in green microalgae, particularly the effects of MS, remain poorly understood. Therefore, we evaluated how salicylates applied at concentrations of 0.1, 1, and 10 µM affect the growth and accumulation of bioactive compounds in a high-productivity clone of Planktochlorella nurekis, combining gas chromatography coupled mass spectrometry (GC-MS) fatty acid profiling with spectrophotometric determination of pigment levels, total phenols, and L-phenylalanine ammonia-lyase (PAL) activity. SA increased cell number and size, whereas 0.1 µM MS resulted in a six-fold gain in cell number. Accordingly, 10 µM MS raised chlorophyll b levels—nearly three-fold (from 76 to 211 µg per g D.W.)—and total carotenoids—roughly four-fold (129 to 520 µg per g D.W.)—while both elicitors significantly increased the monounsaturated fatty acid fraction (from 29% to about 40%). Notably, 10 µM SA lowered the levels of saturated fatty acids. Moreover, 10 µM MS doubled the PAL activity and increased the total phenols by 17% compared to the control. Thus, SA and MS act as effective elicitors of high-value metabolites in P. nurekis. Full article

(This article belongs to the Special Issue High-Value Algae Products, 2nd Edition)

► Show Figures

Graphical abstract

18 pages, 322 KB

Open AccessReview

Fucoxanthin Bioproduction from Marine Diatoms: Regulatory Strategies and Industrial Potential of Phaeodactylum tricornutum and Odontella aurita—A Review

by Man Zhang, Haoyu Li, Feichao Du, Yuhua Li and Haixing Li

Mar. Drugs 2026, 24(8), 282; https://doi.org/10.3390/md24080282 - 16 Aug 2026

Abstract

Fucoxanthin is a high-value marine xanthophyll with a unique epoxy-allene structure, predominantly produced by brown macroalgae and marine diatoms, and additionally reported in other heterokont lineages including chrysophytes and certain haptophytes. As a core light-harvesting pigment, it exhibits multiple bioactivities including lipid-lowering, antioxidant, [...] Read more.

Fucoxanthin is a high-value marine xanthophyll with a unique epoxy-allene structure, predominantly produced by brown macroalgae and marine diatoms, and additionally reported in other heterokont lineages including chrysophytes and certain haptophytes. As a core light-harvesting pigment, it exhibits multiple bioactivities including lipid-lowering, antioxidant, and anti-inflammatory effects, with broad applications in functional foods, dietary supplements, and pharmaceuticals. Currently, over 70% of commercial fucoxanthin is extracted from brown macroalgae such as Saccharina japonica and Undaria pinnatifida. However, due to low endogenous pigment content and significant extraction losses, the industrial yield is only 0.05–0.1% of dry weight, failing to meet the growing downstream demand for stable high-purity supply. Marine diatoms, characterized by short growth cycles, high pigment content, and controllable culture conditions, have emerged as a core direction for industrial upgrading. Among them, Phaeodactylum tricornutum and Odontella aurita are the two most systematically studied high-yield strains with outstanding potential. This review adopts volumetric productivity (mg/(L·d)) as the core evaluation metric, which integrates biomass concentration, pigment content, and production cycle, and reflects industrial efficiency more reliably than single intracellular content data. We summarize high-yield induction methods from the dimensions of nutrient regulation, light optimization, exogenous induction, and strain improvement, and systematically compare downstream processing, safety profiles, and regulatory status between the two diatoms. Furthermore, we evaluate multi-product co-production potential and scale-up performance from a techno-economic perspective. This review provides a side-by-side benchmark of these two marine diatoms, offering a data-driven reference for process development and industrial deployment of microalgae-derived fucoxanthin. Full article

(This article belongs to the Special Issue Algae Research: From Cultivation to Drugs)

► Show Figures

Graphical abstract

24 pages, 7494 KB

Open AccessArticle

Integrated Multi-Omics Analysis of Antarctica Krill Oil in Alleviating DSS-Induced Colitis and Modulating Gut Microbiota in Mice

by Shuyin Yang, Xinnan Zhao, Tiantian Chen, Yichen Lin, Yan Di, Zhijun Tan, Ningning He, Shangyong Li and Jixing Peng

Mar. Drugs 2026, 24(8), 281; https://doi.org/10.3390/md24080281 - 14 Aug 2026

Abstract

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with elusive etiology and limited therapeutic options, accompanied by potential side effects. In this study, to investigate the therapeutic potential of Antarctic krill oil (AKO) in a dextran sulfate sodium (DSS)-induced mouse colitis model, [...] Read more.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with elusive etiology and limited therapeutic options, accompanied by potential side effects. In this study, to investigate the therapeutic potential of Antarctic krill oil (AKO) in a dextran sulfate sodium (DSS)-induced mouse colitis model, animal experiments, molecular assays, transcriptomics, metabolomics, and 16S rRNA gene sequencing were conducted. Our results revealed that supplementation of AKO significantly alleviated colitis symptoms, such as weight loss, and inflammatory responses. Moreover, multi-omics analyses demonstrated that AKO inhibited the PI3K/Akt signaling pathway, remodeled beneficial gut microbiota, and reshaped metabolite profiles associated with glycerolphospholipid metabolism. Remarkably, AKO alleviated DSS-induced colitis, accompanied by coordinated changes in the gut microbiota, metabolites, and transcriptome, which were associated with suppression of key inflammatory pathways. These findings present experimental evidence for the potential of AKO as a marine-based nutritional intervention for UC, and offer novel perspectives on microbiota-targeted therapies for inflammatory diseases. Full article

(This article belongs to the Special Issue Marine Lipidomics and Bioactive Lipids)

► Show Figures

Graphical abstract

29 pages, 1869 KB

Open AccessArticle

Transcriptomic Responses of MRSA to Penicillin-Modulating Phlorotannins Derived from Pelvetia canaliculata

by James Blee, Peter O’Hara, Jialun Wu, Conor O’Byrne, Thomas J. P. Smyth and Owen Kenny

Mar. Drugs 2026, 24(8), 280; https://doi.org/10.3390/md24080280 - 12 Aug 2026

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) infections contribute significantly to the mortality rate associated with antimicrobial resistance, while also increasing medical complications when compared to methicillin-sensitive isolates. Consequently, increasing the efficacy of β-lactams may alleviate the burden associated with this drug–pathogen combination. Dialysed extracts, derived [...] Read more.

Methicillin-resistant Staphylococcus aureus (MRSA) infections contribute significantly to the mortality rate associated with antimicrobial resistance, while also increasing medical complications when compared to methicillin-sensitive isolates. Consequently, increasing the efficacy of β-lactams may alleviate the burden associated with this drug–pathogen combination. Dialysed extracts, derived from Pelvetia canaliculata, were further partitioned to generate phlorotannin enriched extracts (PEEs). Minimum inhibitory concentrations (MICs) of extracts were used to determine the antimicrobial and antibiotic-modulating activity against seven clinical MRSA isolates. Whole-transcriptomic sequencing was carried out to determine potential mechanisms of action on the strongest extract–antibiotic combination against an MRSA isolate, determined by the fractional inhibitory concentration index (FICI). The most pronounced β-lactam modulatory effects were seen in the >100 kDa PEE from P. canaliculata in conjunction with amoxicillin (MIC fold-reductions = 12.8–214), while >30 kDa PEE resulted in the strongest FIC index value when combined with penicillin (0.23), indicating a synergistic effect. Whole-transcriptome analysis of this treatment identified multiple differentially expressed genes (Log2FC +1/−1) of statistical significance (p adj < 0.05), namely related to accelerated autolysis, cell-envelope stability, protein synthesis, DNA replication, iron homeostasis and active transport. This study highlights preliminary transcriptomic evidence of biological processes associated with penicillin modulation by P. canaliculata > 30 kDa PEE, providing a foundation for further investigation of its antibiotic-modulating activity. Full article

(This article belongs to the Special Issue Marine Natural Products with Antibacterial and Antibiofilm Activity)

► Show Figures

Figure 1

12 pages, 6477 KB

Open AccessArticle

Two New Indole Derivatives from the Beibu Gulf Coral-Derived Fungus Pestalotiopsis microspora GXIMD 02530

by Hui Shi, Guihua Yang, Xiaolin Liu, Miaoping Lin, Humu Lu, Chenghai Gao, Yonghong Liu and Xiaowei Luo

Mar. Drugs 2026, 24(8), 279; https://doi.org/10.3390/md24080279 - 12 Aug 2026

Abstract

Two new indole derivatives (1 and 2), along with fourteen known indole and polyketide compounds, were characterized from the Beibu Gulf coral-derived fungus Pestalotiopsis microspora GXIMD 02530. Their structures and absolute configurations were determined by comprehensive spectroscopic analysis, electronic circular dichroism [...] Read more.

Two new indole derivatives (1 and 2), along with fourteen known indole and polyketide compounds, were characterized from the Beibu Gulf coral-derived fungus Pestalotiopsis microspora GXIMD 02530. Their structures and absolute configurations were determined by comprehensive spectroscopic analysis, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction. Structurally, furoindolin A (1) was obtained as a rare racemic 6/5/5 tricyclic indole derivative incorporating a dihydrofuranone ring, which was further separated into a pair of enantiomers by chiral chromatographic resolution. Compounds (±)-1, 3, 4, and 6–12 exhibited inhibition of LPS-induced NF-κB luciferase activities. Phomopsilactone (10) displayed antibacterial activities against Staphylococcus epidermidis, Bacillus subtilis, and Staphylococcus aureus, with MIC values of 15.6, 31.25, and 62.5 μg/mL, respectively. Our findings would expand the chemical variety of indole derivatives and highlight furoindolin A (+)-1 as a promising chemical template for further biosynthetic and anti-inflammatory pharmacological investigation. Full article

(This article belongs to the Special Issue Bioactive Polyketides from Marine Resources)

► Show Figures

Graphical abstract

20 pages, 8673 KB

Open AccessArticle

Pharmacokinetic Profiling Evaluation of Ruditapes philippinarum Polysaccharide

by Meng-Yue Liu, Dong-Li Yin, Jia Yu, Wei-Xia Wang, Sheng-Can Zou, Shuang Zhao, Chun-Ze Zou, Fei Li and Yu-Xi Wei

Mar. Drugs 2026, 24(8), 278; https://doi.org/10.3390/md24080278 - 11 Aug 2026

Abstract

Oral administration represents the primary route for administering polysaccharides. Pharmacokinetics serves as a critical bridge between the administration of polysaccharides and the manifestation of their bioactivities. However, the pharmacokinetic behavior of polysaccharides remains poorly understood. This study aimed to investigate the in vivo [...] Read more.

Oral administration represents the primary route for administering polysaccharides. Pharmacokinetics serves as a critical bridge between the administration of polysaccharides and the manifestation of their bioactivities. However, the pharmacokinetic behavior of polysaccharides remains poorly understood. This study aimed to investigate the in vivo pharmacokinetics of an orally administered Ruditapes philippinarum polysaccharide (ERPP), including its plasma concentration–time profile, tissue distribution, and excretion. Moreover, a sensitive quantitative method was developed using 5-DTAF as a fluorescent probe to quantify ERPP levels in rat plasma and tissues. The results revealed that ERPP was absorbed in the gut (T_max = 3 h), reaching a peak concentration (C_max) of 22.7 ± 2.7 mg/L. Subsequently, it predominantly accumulated in the kidneys, liver, and lungs. Complementarily, near-infrared fluorescence (NIR) imaging provided real-time qualitative visualization of ERPP-Cy5.5 tissue distribution, corroborating the organ-level accumulation pattern observed in the quantitative study. Excretion studies over a 24 h observation window indicated that ERPP was primarily excreted via feces, with 45.7 ± 4.4% of the recovered dose within this period; the complete excretion profile warrants further investigation at extended time points. These findings provide pharmacokinetic insights into the in vivo fate of marine polysaccharides and support further biological evaluation. Full article

(This article belongs to the Section Marine Pharmacology)

► Show Figures

Graphical abstract

48 pages, 2329 KB

Open AccessReview

Healing from the Ocean: Targeting Shared Mechanisms in Autism and Epilepsy Using Algae-Derived Compounds

by Dorit Avni, Orly Weissberg, Noam Pintel and Liat Izraelov

Mar. Drugs 2026, 24(8), 277; https://doi.org/10.3390/md24080277 - 10 Aug 2026

Abstract

Autism spectrum disorder (ASD) and epilepsy are complex, frequently co-occurring neurodevelopmental and neurological disorders that share key mechanisms, such as altered neurotransmission, oxidative stress, neuroinflammation, and gut–brain axis disruption. Despite pharmacological advances, current treatments often provide only partial relief and are associated with [...] Read more.

Autism spectrum disorder (ASD) and epilepsy are complex, frequently co-occurring neurodevelopmental and neurological disorders that share key mechanisms, such as altered neurotransmission, oxidative stress, neuroinflammation, and gut–brain axis disruption. Despite pharmacological advances, current treatments often provide only partial relief and are associated with significant side effects. The comorbidity of ASD and epilepsy, affecting millions worldwide, remains under-recognised and poorly addressed, imposing a profound burden on patients, families, and healthcare systems through reduced quality of life, increased caregiving demands, and substantial social and economic costs. This review highlights the convergent pathways shared between ASD and epilepsy, including immune dysregulation, synaptic dysfunction, and metabolic imbalance, which create opportunities for unified therapeutic strategies. Marine algae have emerged as a sustainable source of bioactive compounds offering a unique potential to address these overlapping pathologies. Algal polyunsaturated fatty acids, carotenoids, polyphenols, polysaccharides, and vitamins have antioxidant, anti-inflammatory, neuroprotective, and microbiota-modulating activities. By addressing both the biological underpinnings and clinical burden of ASD–epilepsy comorbidity, algae-based strategies represent a novel and ecologically sustainable direction for mitigating ASD–epilepsy comorbidity and advancing marine-inspired neurotherapeutics. Full article

(This article belongs to the Special Issue Effects of Marine Natural Products in Brain Health and Metabolic Diseases, 2nd Edition)

► Show Figures

Graphical abstract

26 pages, 23706 KB

Open AccessArticle

Diversity and Bioprospection of Functional Proteins from Sea Anemone Heteractis magnifica Based on Multi-Omics Approach

by Jiao Chen, Zhen Chen, Shibo Sun, Chang Lyu, Ming Li, Yun Song and Bingmiao Gao

Mar. Drugs 2026, 24(8), 276; https://doi.org/10.3390/md24080276 - 7 Aug 2026

Abstract

Sea anemone venom has attracted increasing attention in biomedical research due to its multifarious compounds with biological activities. Although the venom is predominantly made up of proteins, the diversity and complexity of these proteins remain poorly understood. In this work, the proteins derived [...] Read more.

Sea anemone venom has attracted increasing attention in biomedical research due to its multifarious compounds with biological activities. Although the venom is predominantly made up of proteins, the diversity and complexity of these proteins remain poorly understood. In this work, the proteins derived from the tentacle and column of Heteractis magnifica were investigated by integrating transcriptomic and proteomic technologies. A total of 3573 protein sequences from transcriptome databases were identified and clustered into nine functional categories. We also performed proteomic analysis on the proteins identified in H. magnifica, and 339 proteins were found to be present in both datasets. Notably, a comprehensive analysis of six typical categories was implemented, and the representative proteins were explored in depth using multiple alignments, homology modeling and molecular docking. Meanwhile, a few low-copy but functionally intriguing proteins were discovered, highlighting the presence of unconventional components in sea anemone venom. This work provides the first holistic overview of the typical protein families and novel information on functional proteins from H. magnifica, contributing to a deeper understanding of sea anemone proteins and facilitating the discovery of potential proteins for marine drugs or biotechnological tools. Full article

(This article belongs to the Special Issue Bioactive Compounds from Marine Invertebrates)

► Show Figures

Figure 1

Journal Description

Marine Drugs

Latest Articles

Journal Menu

Journal Browser

Highly Accessed Articles

Latest Books

E-Mail Alert

News

Topics

Conferences

Special Issues

Topical Collections

Further Information

Guidelines

MDPI Initiatives

Follow MDPI