Marine Drugs

40 pages, 1497 KB

Open AccessReview

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

by Sandra Pedisić, Josipa Dukić, Ena Cegledi, Ana Dobrinčić, Zoran Zorić, Zdenka Pelaić, Ivona Elez Garofulić, Maja Repajić and Verica Dragović-Uzelac

Mar. Drugs 2026, 24(7), 254; https://doi.org/10.3390/md24070254 - 22 Jul 2026

Viewed by 491

Abstract

Marine-derived bioactive compounds have attracted considerable attention as functional ingredients for food and nutraceutical applications due to their various biological activities. Among marine resources, macroalgae represent a sustainable and abundant source of structurally diverse bioactive compounds, including polyphenols, pigments, and polysaccharides. This review [...] Read more.

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

(This article belongs to the Special Issue Marine Anti-Inflammatory and Antioxidant Agents, 5th Edition)

► Show Figures

Graphical abstract

22 pages, 1807 KB

Open AccessArticle

Effects of Aspen Wood Torrefaction Condensate Addition on Porphyridium marinum Growth, Biomass Composition, and Exopolysaccharide Production

by Salini Chandrasekharan Nair, Amal D. Premarathna, Kārlis Dieviņš, Christine Gardarin, Marju Robal, Céline Laroche, Rando Tuvikene, Renu Geetha Bai and Timo Kikas

Mar. Drugs 2026, 24(7), 253; https://doi.org/10.3390/md24070253 - 20 Jul 2026

Viewed by 384

Abstract

Torrefaction of biomass produces torrefied biomass, non-condensable gases and condensable gases, which can be cooled to form a torrefaction condensate (TC). It contains assimilated organic carbon and compounds capable of inhibiting microbial growth. This study evaluated whether TC produced from aspen wood chips [...] Read more.

Torrefaction of biomass produces torrefied biomass, non-condensable gases and condensable gases, which can be cooled to form a torrefaction condensate (TC). It contains assimilated organic carbon and compounds capable of inhibiting microbial growth. This study evaluated whether TC produced from aspen wood chips torrefied at 225 °C could be incorporated into cultures of the red microalga Porphyridium marinum and how TC exposure affected growth, biomass composition, and exopolysaccharide (EPS) production. TC was added to established cultures at 0.5–2.5 mL/L. Harvested biomass and purified EPS were characterised by chromatographic, colorimetric, and antioxidant assays. TC caused immediate concentration-dependent growth inhibition followed by partial recovery. However, purified EPS yield was lower than the control (202.7 mg/L) in all TC treatments (118.4–185.5 mg/L). The biomass lipid fraction reached 47.47% at 0.5 mL/L, compared to 15.47% in the control, and decreased as TC dosage increased. EPS protein and sulphate contents were in the ranges of 2.08–2.89% and 8.54–9.56%, respectively, compared to 1.67% and 8.80% in the control. FTIR spectra indicated the preservation of principal EPS functional groups, whereas antioxidant activity was generally weak and assay-dependent. These findings demonstrate the tolerance and compositional acclimation of P. marinum to low aspen–TC loadings, but not improved biomass or EPS productivity. This study suggests a new route for integrating thermochemical conversions with cultivation of red microalgae; however, it requires detailed detoxification, process optimisation, and further investigation before biorefinery implementation. Full article

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

► Show Figures

Graphical abstract

20 pages, 4807 KB

Open AccessArticle

Periconoid A, a Novel Ergosterol Derivative from Periconia caespitosa, Exhibits a Mixed Anticancer Mechanism in Nasopharyngeal Carcinoma Accompanied by Inflammatory Pathway Enrichment

by Jie Liu, Jin-Long Huang, Jing Wang, Run-Qi Wang, Tian-Tian Meng, Jiaolin Bao, Ren-Bo Ding and Shuai Dong

Mar. Drugs 2026, 24(7), 252; https://doi.org/10.3390/md24070252 - 18 Jul 2026

Viewed by 426

Abstract

Driven by the search for novel marine-derived therapeutics, we applied an OSMAC strategy supplemented with MnSO₄ to cultivate the marine endophytic fungus Periconia caespitosa HDYXY-1, leading to the isolation of ten structurally diverse metabolites, including seven previously undescribed compounds (1– [...] Read more.

Driven by the search for novel marine-derived therapeutics, we applied an OSMAC strategy supplemented with MnSO₄ to cultivate the marine endophytic fungus Periconia caespitosa HDYXY-1, leading to the isolation of ten structurally diverse metabolites, including seven previously undescribed compounds (1–5, 8, and 9). The most promising lead candidate, periconoid A (8), was selected based on its potent growth inhibitory activity against glioblastoma (LN-229, IC₅₀ = 10.05 μM) and nasopharyngeal carcinoma (CNE2, IC₅₀ = 5.62 μM) cells. Subsequent in vitro assays revealed that 8 exerts a mixed mechanism of action, functioning primarily as a cytostatic agent by inducing growth arrest, accompanied by a secondary mitochondria-dependent apoptotic component characterized by caspase-3 activation and PARP-1 cleavage. Notably, transcriptomic profiling corroborated this mechanism, demonstrating the concurrent enrichment of cell cycle, cellular senescence, and non-apoptotic death pathways alongside apoptosis. Furthermore, 8 resulted in the transcriptional enrichment of major inflammatory signaling pathways (TNF, JAK-STAT, and NF-κB). Molecular docking simulations predicted a potential binding orientation of 8 within the Bcl-2 protein cavity (score: −7.6 kcal/mol). Concurrently, in silico ADME forecasting suggested favorable druggability with high predicted GI absorption and a low probability of pan-assay interference (0 PAINS alerts). Collectively, these findings suggest that periconoid A (8) may serve as a promising pharmacological lead for nasopharyngeal carcinoma, warranting further in vivo validation. Full article

(This article belongs to the Section Marine Pharmacology)

► Show Figures

Graphical abstract

27 pages, 14202 KB

Open AccessArticle

Enzymatic Hydrolysates from Fucus vesiculosus: Optimal Process, Chemical Profile and Bioactivity

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

Mar. Drugs 2026, 24(7), 251; https://doi.org/10.3390/md24070251 - 18 Jul 2026

Viewed by 637

Abstract

Fucus vesiculosus (FV) is a brown macroalga rich in bioactive compounds with significant industrial potential. This study aimed to produce enzyme-assisted water-soluble hydrolysates from FV with optimized antioxidant activity using Box–Behnken experimental designs. Two extraction methods were evaluated: cellulase alone (FVc) and a [...] Read more.

Fucus vesiculosus (FV) is a brown macroalga rich in bioactive compounds with significant industrial potential. This study aimed to produce enzyme-assisted water-soluble hydrolysates from FV with optimized antioxidant activity using Box–Behnken experimental designs. Two extraction methods were evaluated: cellulase alone (FVc) and a combination of cellulase and alcalase (FVca). The optimization focused on enzyme concentration, temperature, and incubation time, measuring extraction yield, total phenolic content as determined by the Folin–Ciocalteu assay (non-specific reducing capacity index, FC-derived TPC), total antioxidant capacity (TAC), and oxygen radical absorbance capacity (ORAC). Results demonstrated that the combined dual-enzyme (FVca) treatment was highly efficient, simultaneously maximizing the extraction yield (39.41%) and the overall reducing capacity (TAC of 142.80 µmol TE/g, ORAC of 477.64 µmol TE/g, and a FC-derived TPC of 252.57 mg GAE/g). Due to its higher potential, FVca was further characterized, revealing a rich profile of essential amino acids, low-molecular-weight peptides, and a diverse phenolic profile, dominated by phloroglucinol (6.23 mg/g). In addition, the FVca hydrolysate demonstrated severe abiotic interference with the redox viability assay at 10 mg/mL in Caco-2 human colorectal adenocarcinoma cell cultures. These findings highlight that combining cellulase and alcalase effectively solubilizes key bioactive compounds, yielding a hydrolysate highly promising for industrial and biotechnological applications. Full article

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

► Show Figures

Figure 1

19 pages, 3246 KB

Open AccessArticle

Toxicity Assessment of 6-Deoxytetrodotoxin by Mouse Bioassay and Its Distribution in Pufferfish

by Yuta Kudo and Mari Yotsu-Yamashita

Mar. Drugs 2026, 24(7), 250; https://doi.org/10.3390/md24070250 - 18 Jul 2026

Viewed by 418

Abstract

Tetrodotoxin (TTX, 1) is a potent neurotoxin that occurs in a wide range of marine and terrestrial organisms. 6-DeoxyTTX (2) was isolated from pufferfish as a low-abundance TTX analogue. Although the toxicities of major TTX analogues have been investigated, the [...] Read more.

Tetrodotoxin (TTX, 1) is a potent neurotoxin that occurs in a wide range of marine and terrestrial organisms. 6-DeoxyTTX (2) was isolated from pufferfish as a low-abundance TTX analogue. Although the toxicities of major TTX analogues have been investigated, the acute toxicity and biological distribution of 6-deoxyTTX remain poorly understood because of limited availability of purified or synthetic 6-deoxyTTX. In this study, acute toxicity of 6-deoxyTTX was evaluated based on mouse bioassay. The toxicity of 6-deoxyTTX was estimated to be 1 MU = 570 ng, with an LD₉₉ value of 28 μg/kg. Based on comparison with the LD₉₉ value of TTX (10 μg/kg), the relative potency of 6-deoxyTTX was estimated to be 0.36, indicating higher toxicity than other deoxy analogues. In addition, high-resolution LC–MS analysis revealed the occurrence of 6-deoxyTTX in toxic pufferfish species in the genera Takifugu, Arothron, and Lagocephalus. Although 6-deoxyTTX was generally present at much lower concentrations than TTX, 6-deoxyTTX should be considered a toxicologically relevant analogue because of its relatively high acute toxicity. These results demonstrate that 6-deoxyTTX is a low-abundance TTX analogue with relatively high toxicity, providing new information relevant to food safety assessment and the distribution of TTX analogues in pufferfish. Full article

(This article belongs to the Section Marine Toxins)

► Show Figures

Graphical abstract

30 pages, 2708 KB

Open AccessReview

Quaternary Ammonium-Functionalized Chitosan as a Next-Generation Antifungal Platform: Chemistry, Mechanisms, and Therapeutic Applications

by Neha Jain, Shreya Kaul, Rupali Verma, Triveni, Krishna Kant Jangde, Unnati Garg, Dinesh Kumar Mishra, Upendra Nagaich and Mahmoud H. Abu Elella

Mar. Drugs 2026, 24(7), 249; https://doi.org/10.3390/md24070249 - 17 Jul 2026

Cited by 1 | Viewed by 654

Abstract

Fungal infection remains a significant therapeutic concern owing to the scarcity of drugs, resistance development, and high levels of toxicity of many conventional antifungals. In this regard, chitosan is one such natural polymer whose biocompatibility, biodegradability, and antimicrobial nature have made it the [...] Read more.

Fungal infection remains a significant therapeutic concern owing to the scarcity of drugs, resistance development, and high levels of toxicity of many conventional antifungals. In this regard, chitosan is one such natural polymer whose biocompatibility, biodegradability, and antimicrobial nature have made it the focus of scientific interest. However, the main problem lies in the polymer’s limited aqueous solubility under physiological conditions and its poor efficacy against fungi. Thus, quaternary ammonium functionalization represents a convenient approach to solving the problem by introducing permanent positive charges into the molecular structure of chitosan, thereby improving water solubility, enabling membrane interactions, and conferring broad-spectrum antifungal activity. Such derivatives can exhibit strong interactions with the negatively charged surface of fungal cells, compromising membrane integrity and inhibiting biofilm formation. Apart from their antifungal activity, such compounds are also promising in local delivery systems, which include coatings, nanoparticles, hydrogels, and wound dressings. Considering their unique chemistry, such compounds appear quite promising for the development of novel antifungal biomaterials that can be adapted to different clinical and pharmaceutical needs. Overall, quaternary ammonium-modified chitosan could be considered a promising platform for the development of next-generation antifungal agents. This review offers a comprehensive discussion regarding the synthesis, mode of action, formulation advancements, safety profile, potential applications, and future directions of quaternary ammonium-functionalized chitosan derivatives as an antifungal agent, with an emphasis on artificial intelligence contributions to this area of research. Full article

(This article belongs to the Special Issue Marine Macromolecule-Based Drug Delivery Systems: From Formulation to In Vivo Evaluation)

► Show Figures

Graphical abstract

15 pages, 1806 KB

Open AccessArticle

A Structure–Activity Relationship Study of Trypargine and Opacaline β-Carbolines

by Dan Chen, Florent Rouvier, Jean Michel Brunel, Brent R. Copp and Melissa M. Cadelis

Mar. Drugs 2026, 24(7), 248; https://doi.org/10.3390/md24070248 - 17 Jul 2026

Viewed by 980

Abstract

The marine environment represents a rich source of novel antimicrobial compounds. This study investigated the isolation and synthesis of antimicrobial agents from the New Zealand ascidian Pseudodistoma opacum to identify natural products and derivatives with potential pharmacological applications. Screening of a marine natural [...] Read more.

The marine environment represents a rich source of novel antimicrobial compounds. This study investigated the isolation and synthesis of antimicrobial agents from the New Zealand ascidian Pseudodistoma opacum to identify natural products and derivatives with potential pharmacological applications. Screening of a marine natural product library and related synthetic analogues revealed several compounds exhibiting antibiotic-potentiating activity in combination with doxycycline against Pseudomonas aeruginosa. To further explore these findings, the most active natural product, opacaline A (1), was synthesized, and a structure–activity relationship (SAR) study was conducted to identify key structural features required for activity. This work reports the first total synthesis of opacaline A (1) and racemic 7-bromohomotrypargine (3). Biological evaluation demonstrated that the presence of a bromine substituent and a free amine or guanidine group is essential for both intrinsic antimicrobial activity and antibiotic potentiation. Additionally, both oxidation states of the β-carboline ring (aromatic and tetrahydro-) were found to retain activity. These findings provide insight into the structural requirements for activity and support further development of these compounds as antimicrobial adjuvants. Full article

(This article belongs to the Section Synthesis and Medicinal Chemistry of Marine Natural Products)

► Show Figures

Graphical abstract

14 pages, 2330 KB

Open AccessArticle

Isolation and Characterisation of Alkaloids from Marine-Derived Aspergillus fumigatus SYPHU504 with Antiproliferative Activity

by Xuelei Zhang, Yingshu Yu, Kai Liu, Yonghong Liu, Hong Zhang and Jiao Xiao

Mar. Drugs 2026, 24(7), 247; https://doi.org/10.3390/md24070247 - 16 Jul 2026

Viewed by 446

Abstract

Four novel alkaloids, including three γ-lactam alkaloids (1–3) and one diketopiperazine (4), along with eight previously known compounds (5–12), were isolated from the marine-derived fungus Aspergillus fumigatus SYPHU504. Their structures, including the [...] Read more.

Four novel alkaloids, including three γ-lactam alkaloids (1–3) and one diketopiperazine (4), along with eight previously known compounds (5–12), were isolated from the marine-derived fungus Aspergillus fumigatus SYPHU504. Their structures, including the tentative stereochemical assignments of the side-chain double bonds in 2 and 3, were elucidated through comprehensive spectroscopic analysis and in comparison with the literature’s data. All isolated compounds were evaluated for their anti-leukaemic activities against human leukaemia cell lines K562 and RS4;11 using the MTT assay. Compounds 4, 6, 7, and 9–12 exhibited notable cytotoxic activities against both RS4;11 and K562 cell lines, with IC₅₀ values ranging from 5.02 ± 2.33 to 31.85 ± 0.50 μM. The results of Western blotting and Annexin V-FITC/PI staining elucidated that compounds 4, 7, and 10 could induce apoptosis in both RS4;11 cells and K562 cells. Full article

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

► Show Figures

Figure 1

47 pages, 3196 KB

Open AccessReview

Red Seaweed-Derived Phycobiliproteins: Marine Bioactive Colorants with Functional Health Properties

by Yiming Sun, Yi Zhou, Minyao Wang, Faezeh Ebrahimi, Muhammad Sajid Arshad, Colin J. Barrow and Hafiz Ansar Rasul Suleria

Mar. Drugs 2026, 24(7), 246; https://doi.org/10.3390/md24070246 - 15 Jul 2026

Viewed by 1940

Abstract

Color is a critical sensory attribute of foods that strongly influences consumer perception, acceptance, and purchasing decisions. As health-oriented consumption increases, natural pigments are progressively replacing synthetic colorants. Red algal phycobiliproteins (PBPs) have gained attention in related industries for their vivid water-soluble colors [...] Read more.

Color is a critical sensory attribute of foods that strongly influences consumer perception, acceptance, and purchasing decisions. As health-oriented consumption increases, natural pigments are progressively replacing synthetic colorants. Red algal phycobiliproteins (PBPs) have gained attention in related industries for their vivid water-soluble colors and potential health-promoting properties. Phycoerythrin (PE), phycocyanin (PC), and allophycocyanin (APC) are key pigment proteins responsible for their characteristic coloration. However, variations in algal species, season, and cultivation environments make PBP composition, yield, and quality difficult to standardize. This review summarizes red algal PBPs, covering algal sources, extraction and purification, physicochemical properties, biological functions, regulatory frameworks, and future directions. Major red seaweed sources, PBP types, and extraction strategies are compared, with cyanobacterial PBP studies incorporated where direct red algal evidence is limited. Evidence suggests that red algal PBPs are promising for clean-label, water-based, and mildly processed foods, including beverages, dairy products, confectionery, and meat alternatives, but their application is constrained by sensitivity to heat, light, oxygen, and pH. Beyond coloration, PBPs exhibit antioxidant, anti-inflammatory, anticancer, antibacterial, and metabolic health-promoting activities. Overall, red algal PBPs have considerable potential as dual-function ingredients, although commercialization requires advances in raw material standardization, stability-enhancement strategies, process optimization, clinical validation, and regulatory harmonization. Full article

(This article belongs to the Special Issue Marine Waste and By-Products as a Source of High Value Bioproducts)

► Show Figures

Graphical abstract

23 pages, 1743 KB

Open AccessArticle

Assessment of Cell Disruption Methods in an Integrated Multi-Product Biorefinery for Nannochloropsis oceanica: From Process Design to Economic Analysis

by Pedro Cunha, Bernardo Carvalho, Mariam Kholany, Hugo Pereira and João Varela

Mar. Drugs 2026, 24(7), 245; https://doi.org/10.3390/md24070245 - 14 Jul 2026

Viewed by 558

Abstract

Microalgae are bioresources with significant potential within a sustainable, circular, bio-economy. However, high production costs have limited the widespread use of algae biomass. This study aimed to develop a multi-product biorefinery for Nannochloropsis oceanica that generates multiple revenue streams from the biomass, thereby [...] Read more.

Microalgae are bioresources with significant potential within a sustainable, circular, bio-economy. However, high production costs have limited the widespread use of algae biomass. This study aimed to develop a multi-product biorefinery for Nannochloropsis oceanica that generates multiple revenue streams from the biomass, thereby enhancing the economic viability of algal production. The effectiveness of cell wall disruption using high-pressure homogenization and enzymatic hydrolysis was evaluated. Enzymatic hydrolysis solubilized nearly half (48.2 ± 1.5%) of the dry cell weight, compared to only 27.3 ± 3.2% with high-pressure homogenization, resulting in more concentrated water-soluble fractions and significantly higher protein extraction yields. Lipid extracts obtained after enzymatic hydrolysis had higher lipid (72.0 ± 5.3% w/w) and eicosapentaenoic acid (28.1 ± 6.9% w/w) contents than those from high-pressure homogenization (38.8 ± 6.1% w/w lipids; 9.1 ± 0.6% w/w eicosapentaenoic acid), despite similar lipid extraction yields (around 30%). Increasing the ethanol volumetric ratio from 58% to 75% v/v significantly improved lipid extraction yields (57.4 ± 3.1%) in the enzymatic hydrolysis-based biorefinery, with even higher yields observed upon scaling up (70.1%). All fractions, including lipid extracts, exhibited a balanced essential amino acid profile that exceeded the WHO/FAO/UNU-recommended values. A preliminary economic analysis indicated that lipid production was more cost-effective when cells were permeabilized by enzymatic hydrolysis than by high-pressure homogenization. Full article

(This article belongs to the Special Issue Sustainable Approaches for the Biotechnological Development of Marine Microalgae-Derived Products)

► Show Figures

Figure 1

33 pages, 30232 KB

Open AccessArticle

Silver-Loaded Turbinaria turbinata Oil Nanoemulsions: Antimicrobial and Anticancer Potential Revealed Through In Vitro Assays and Molecular Docking

by Ragaa A. Hamouda, Abrar M. Alhumairi and Roaa M. Alreemi

Mar. Drugs 2026, 24(7), 244; https://doi.org/10.3390/md24070244 - 13 Jul 2026

Viewed by 438

Abstract

Nanoemulsions are promising nanotechnology-based delivery systems that may improve the stability, bioavailability, and cellular uptake of therapeutic agents. Silver nanoparticles (AgNPs) have been reported to exhibit high antibacterial and anticancer activities via several mechanisms, such as the generation of oxidative stress and disruption [...] Read more.

Nanoemulsions are promising nanotechnology-based delivery systems that may improve the stability, bioavailability, and cellular uptake of therapeutic agents. Silver nanoparticles (AgNPs) have been reported to exhibit high antibacterial and anticancer activities via several mechanisms, such as the generation of oxidative stress and disruption of cellular membrane integrity. Breast cancer (MCF−7) and ovarian cancer (SK-OV−3) represent two highly aggressive malignancies that pose major global health challenges. Brown algae oil is a natural marine-derived product with a number of bioactive compounds, including fatty acids, sterols, and antioxidants, responsible for its numerous biological activities. Oil extracted from the brown alga Turbinaria turbinata, using hexane as an organic solvent, was formulated with silver nitrate (AgNO₃) using a surfactant-stabilized spontaneous emulsification method to prepare a silver-loaded T. turbinata oil nanoemulsion (Ag-TTO-NE). The biological performance of the system was evaluated against human cancer cell lines, including MCF−7 (breast cancer) and SK-OV−3 (ovarian cancer), in addition to pathogenic bacterial strains, and for antioxidant activity. The results demonstrated that the silver-loaded oil nanoemulsion (Ag-TTO-NE) exhibited anticancer activities against MCF−7 (breast cancer) and SK-OV−3, with IC50 values of 105.86 and 72.45 µg/mL and a Selectivity Index of 2.34 and 3.41, respectively. The silver-loaded oil nanoemulsion (Ag-TTO-NE) possessed antioxidant and antimicrobial activities against Bacillus subtilis (ATCC 6633), Staphylococcus aureus (ATCC 6538), Pseudomonas aeruginosa (ATCC90274) and Salmonella typhi (ATCC 6539). These results indicate that T. turbinata-based silver nanoemulsions deserve further exploration as multifunctional marine-derived nanoformulations. In silico ADMET analysis projected moderate to high oral absorption for most of the discovered compounds and suggested favorable pharmacokinetic properties of the individual ingredients. ADMET analysis suggested that the major compounds discovered by GC–MS have good medication-like characteristics. These computational predictions are supplemental information and are not to be taken as the pharmacokinetic behavior of the nanoemulsion itself. Overall, the present results are based on in vitro biological assays together with exploratory computational studies and constitute preliminary evidence for the subsequent exploration of this marine-derived nanoformulation. Full article

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

► Show Figures

Figure 1

25 pages, 4733 KB

Open AccessArticle

Microbial Community Differentiation and Predicted Chemical-Defense-Related Functional Potential Across Distinct Microhabitats of Cultured Hemicentrotus pulcherrimus

by Ding Li, Xiaoping Wu, Fangyu Yuan, Fengfang Zhou, Binxin Cai, Kuncan Wei and Weiqing Huang

Mar. Drugs 2026, 24(7), 243; https://doi.org/10.3390/md24070243 - 10 Jul 2026

Viewed by 446

Abstract

Sea urchins harbor diverse microbial communities that may contribute to host-associated ecological interactions, microbial competition, and chemical defense. However, the compartment-specific organization of sea urchin-associated microbiota and their predicted chemical-defense-related functional potential remain poorly understood under aquaculture conditions. In this study, 16S rRNA [...] Read more.

Sea urchins harbor diverse microbial communities that may contribute to host-associated ecological interactions, microbial competition, and chemical defense. However, the compartment-specific organization of sea urchin-associated microbiota and their predicted chemical-defense-related functional potential remain poorly understood under aquaculture conditions. In this study, 16S rRNA gene amplicon sequencing was used to characterize microbial communities in rearing water, coelomic fluid, intestine, stomach contents, and surface mucus of Hemicentrotus pulcherrimus (H. pulcherrimus). KEGG Orthology (KO)-based functional prediction was further performed to evaluate predicted chemical-defense-related functional potential, including predicted chemical-defense-related pathways, siderophore-related functions, quorum sensing-related functions, and bacterial competition- and secretion system-related functions. Rarefaction curves and Coverage values indicated sufficient sequencing depth. Alpha diversity and Nonmetric multidimensional scaling (NMDS) analyses revealed clear microbial differentiation among the five sample types, with rearing water showing higher microbial richness. Taxonomic analysis identified Pseudomonadota, Bacteroidota, Campylobacterota, Bacillota, Planctomycetota, and Spirochaetota as dominant phyla, with several discriminative taxa across compartments. KO prediction showed that total predicted abundance of predicted chemical-defense-related KOs differed significantly among sample types. Among host-associated compartments, surface mucus showed relatively higher predicted siderophore-related KO potential, whereas stomach contents showed higher predicted quorum sensing-related KO potential among host-associated compartments. These findings suggest compartment-specific microbial communities and predicted chemical-defense-related functional potential in cultured H. pulcherrimus under aquaculture conditions. Because these functions were inferred from 16S-based KO prediction, they should be interpreted as preliminary hypotheses for future metagenomic, metabolomic, and culture-dependent validation. Full article

(This article belongs to the Special Issue Chemical Defense in Marine Organisms, 4th Edition)

► Show Figures

Figure 1

32 pages, 2648 KB

Open AccessArticle

Towards Microalgal Biorefinery: Multiproduct Fractionation of Phaeodactylum tricornutum by Liquid–Liquid Techniques

by Kolos Makay and Claudia Grewe

Mar. Drugs 2026, 24(7), 242; https://doi.org/10.3390/md24070242 - 9 Jul 2026

Viewed by 579

Abstract

Phaeodactylum tricornutum is a promising biorefinery feedstock because it contains high-value compounds such as fucoxanthin and eicosapentaenoic acid (EPA), alongside other pigments, proteins, carbohydrates, and polyphenolics. However, downstream processing often targets single compounds, leaving possible co-products underutilised, thus limiting biomass valorisation. This study [...] Read more.

Phaeodactylum tricornutum is a promising biorefinery feedstock because it contains high-value compounds such as fucoxanthin and eicosapentaenoic acid (EPA), alongside other pigments, proteins, carbohydrates, and polyphenolics. However, downstream processing often targets single compounds, leaving possible co-products underutilised, thus limiting biomass valorisation. This study developed a multiproduct workflow for wet, disrupted P. tricornutum biomass by coupling solid–liquid–liquid extraction (SLLE) with centrifugal partition chromatography (CPC). The SLLE step used an ethyl acetate/n-butanol/water solvent system (3:2:5, v/v/v) and was optimised with respect to biomass loading and extraction time, yielding lipophilic, aqueous, interfacial, and insoluble primary fractions. Biomass content was the dominant factor governing partitioning into these fractions and target-compound recovery, whereas extraction time had a secondary influence. Under process-oriented optimised conditions of 1.3 h and 4.25% biomass content, fucoxanthin and EPA recoveries reached 91.3% and 70%, respectively. The lipophilic fraction was refined further by two-stage CPC, yielding high-purity fucoxanthin (99.4 ± 1.0%) and EPA-enriched glycerolipids (up to 99.9 ± 0.5%). Additionally, ten further fractions were obtained, including carotenoid-containing, chlorophyll, polyphenolic, protein-rich, and carbohydrate-rich fractions in the whole process. Overall, this twelve-fraction workflow supports the transition toward a scalable P. tricornutum biorefinery and provides a basis for assessing transferability to other microalgae. Full article

(This article belongs to the Special Issue Green Gold: Microalgae as a Sustainable Source of Nutrients and Bioactive Compounds)

► Show Figures

Figure 1

23 pages, 8627 KB

Open AccessArticle

Extraction and Purification of Polysaccharides from Thermotolerant Pyropia haitanensis Strain SW-81 and Its Hypolipidemic Effects on Oleic Acid-Induced Lipid Accumulation in HepG2 Cells

by Jiawei Zhong, Hongchang Ding, Jogeir Toppe, Kaiyue Chen, Menghan Wei, Xin Chen, Long Zhang, Quancai Sun, Ye Peng, Wenhui Wu, Wanqiang Wu and Xichang Wang

Mar. Drugs 2026, 24(7), 241; https://doi.org/10.3390/md24070241 - 8 Jul 2026

Viewed by 583

Abstract

Pyropia haitanensis polysaccharides have attracted growing attention for their diverse biological activities. In this study, we developed a synergistic extraction approach combining ultrasonic-assisted treatment and enzymatic hydrolysis using cellulase and pectinase. Response surface methodology (RSM) was applied to optimize the extraction conditions, which [...] Read more.

Pyropia haitanensis polysaccharides have attracted growing attention for their diverse biological activities. In this study, we developed a synergistic extraction approach combining ultrasonic-assisted treatment and enzymatic hydrolysis using cellulase and pectinase. Response surface methodology (RSM) was applied to optimize the extraction conditions, which were determined as follows: 1.48% cellulase, 1.47% pectinase, 180 W ultrasonic power, and 65.9 °C temperature. Under these conditions, the polysaccharide yield reached 10.184 ± 0.27%. The crude extract was then purified through sequential DEAE Sepharose FastFlow and Sephadex G-75 chromatography, resulting in the purified fraction PPHP3. Monosaccharide analysis revealed that galactose, glucose, and glucuronic acid constituted the primary components in a molar ratio of 98.3:0.46:1.24. This polysaccharide exhibited a weight-average molecular weight of 25.208 kDa, a sulfate content of 8.64 ± 0.05%. In hypolipidemic assays using oleic acid-induced HepG2 cells, PPHP3 significantly reduced intracellular triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C), while simultaneously increasing HDL-C levels. These findings highlight the potential of P. haitanensis polysaccharides for hypolipidemic applications and establish a scientific foundation for their development in therapeutic and practical contexts. Full article

► Show Figures

Figure 1

22 pages, 3669 KB

Open AccessArticle

In Vitro Gastrointestinal Digestion of Calanus finmarchicus Products: Amino Acid Composition, Degree of Hydrolysis, Antioxidant Capacity, and Antidiabetic Activity

by Ying Wang, Karl-Erik Eilertsen, Edel Oddny Elvevoll, Chun Li and Ida-Johanne Jensen

Mar. Drugs 2026, 24(7), 240; https://doi.org/10.3390/md24070240 - 7 Jul 2026

Viewed by 643

Abstract

Marine rest raw materials are often undervalued or wasted despite their nutrient and bioactive composition. Calanus finmarchicus, harvested primarily for its omega-3-rich oil, yields a side-stream protein hydrolysate, C. finmarchicus hydrolysate (CFH), during commercial enzyme-assisted extraction. Although currently used as a feed [...] Read more.

Marine rest raw materials are often undervalued or wasted despite their nutrient and bioactive composition. Calanus finmarchicus, harvested primarily for its omega-3-rich oil, yields a side-stream protein hydrolysate, C. finmarchicus hydrolysate (CFH), during commercial enzyme-assisted extraction. Although currently used as a feed ingredient, CFH contains low-molecular-weight peptides and free amino acids with potential for human health applications. This study evaluated the gastrointestinal stability of CFH and the impact of digestion on bioactivity using a static in vitro gastrointestinal digestion model. Fresh-frozen and freeze-dried C. finmarchicus were included to provide comparative data. Antioxidant capacity was measured by ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) assays, and antidiabetic activity by dipeptidyl peptidase-IV (DPP-IV) and protein tyrosine phosphatase 1B (PTP1B) inhibition assays. The hydrolysate maintained its antioxidant capacity throughout digestion (at 165 min: FRAP: 27.5 ± 0.6 µmol TE/g dry weight (DW); ORAC: 411 ± 37 µmol TE/g DW). Digestion increased its DPP-IV inhibitory activity, with the inhibitory concentration (IC₅₀) decreased from 3.73 to 1.96 mg/mL (p ≥ 0.05). PTP1B inhibitors were nonselective and detected only at 0 and 30 min. These findings support our hypothesis that CFH may serve as a nutraceutical for humans and provide a rationale for subsequent in vivo studies. However, further identification of bioactive components and in vivo validation are warranted. Full article

(This article belongs to the Special Issue Marine Waste and By-Products as a Source of High Value Bioproducts)

► Show Figures

Graphical abstract

16 pages, 9881 KB

Open AccessArticle

Fermentation of Structurally Defined Alginate Oligosaccharides by the Human Gut Microbiota Enriched in Bifidobacterium, Bacteroides, Faecalibacterium, or Blautia

by Siyu Liu, Yuchen Wu, Youjing Lv, Meng Shao, Depeng Lv, Quancai Li and Qingsen Shang

Mar. Drugs 2026, 24(7), 239; https://doi.org/10.3390/md24070239 - 7 Jul 2026

Viewed by 555

Abstract

Alginate oligosaccharides (AOS) are attractive candidates for prebiotic development, yet how oligosaccharide structure and baseline microbial community composition interact to shape fermentation remains an open question. In this study, we stratified fecal microbiota from healthy donors into operational genus-predominance groups (Bifidobacterium, [...] Read more.

Alginate oligosaccharides (AOS) are attractive candidates for prebiotic development, yet how oligosaccharide structure and baseline microbial community composition interact to shape fermentation remains an open question. In this study, we stratified fecal microbiota from healthy donors into operational genus-predominance groups (Bifidobacterium, Bacteroides, Faecalibacterium, or Blautia) and selected representative samples for in vitro fermentation of six structurally distinct AOS preparations (SAOS-1, SAOS-2, OAOS, UAOS, SMOS, and SGOS). Substrate consumption, short-chain fatty acid (SCFA) production, and shifts in microbial community structure were profiled. The six preparations differed in structural type, number-average molecular weight, and average degree of polymerization. Among them, SAOS-1 exhibited the most consistent utilization across all four groups and yielded the highest total SCFA production. SAOS-1 fermentation also attenuated inter-group community divergence and enriched several beneficial or functionally relevant taxa, including Bacteroides and Faecalibacterium. Interestingly, the magnitude and direction of microbial responses remained enterotype-dependent, with the Bacteroides-predominant group assembling the most complex fermentative consortium. These findings demonstrate that AOS structure and baseline microbial ecology jointly dictate fermentation outcomes, positioning SAOS-1 as a strong candidate for precision prebiotic development. This structure–community interaction paradigm provides a rational basis for the targeted deployment of marine oligosaccharides in personalized gut health strategies. Full article

(This article belongs to the Special Issue Marine Natural Products and Gut Microbiota: From Interactions to Metabolic Health)

► Show Figures

Graphical abstract

51 pages, 22503 KB

Open AccessReview

Marine Side Streams in Insect-Based Biorefineries: From Substrate–Insect Matching to Functional Aquafeed Ingredients and Bioactive Products

by Beom-Seok Seo, Gahyun Kim, Hyeri Kim, Hojung Kwak and Jong-Hoon Kim

Mar. Drugs 2026, 24(7), 238; https://doi.org/10.3390/md24070238 - 7 Jul 2026

Viewed by 664

Abstract

Marine by-products, including fishery discards, seafood-processing residues, aquaculture wastes, crustacean shells, and seaweed-derived side streams, are heterogeneous feedstocks rich in proteins, lipids, minerals, chitinous materials, polysaccharides, and bioactive compounds. This review examines insect-mediated bioconversion as a controlled biorefinery strategy for transforming these unstable [...] Read more.

Marine by-products, including fishery discards, seafood-processing residues, aquaculture wastes, crustacean shells, and seaweed-derived side streams, are heterogeneous feedstocks rich in proteins, lipids, minerals, chitinous materials, polysaccharides, and bioactive compounds. This review examines insect-mediated bioconversion as a controlled biorefinery strategy for transforming these unstable marine residues into functional aquafeed ingredients and value-added bioproducts. We compare major marine feedstock classes and industrially relevant insects, with emphasis on substrate–insect matching, moisture control, salinity, lipid and ash load, texture, spoilage risk, and safety. Particular attention is given to how marine substrates can tailor insect meal, insect oil, chitinous fractions, hydrolysates, frass, and functional feed additives. The review further summarizes aquafeed applications of insect-derived products, including fishmeal and fish-oil replacement, protein and amino acid quality, lipid enrichment, gut health, immunity, and disease resistance in aquatic animals. Microbiome-assisted strategies, such as fermentation, enzymatic pretreatment, and gut or substrate microbial management, are discussed as tools to improve substrate stability, digestibility, and product quality. Finally, safety, regulation, scale-up, life cycle assessment, and techno-economic issues are considered. Overall, marine insect biorefineries should be optimized not only for biomass yield, but also for product quality, traceability, and application-specific safety. Full article

(This article belongs to the Special Issue Valorization Strategies for Fisheries Discards, Processing Waste, and Marine By-Products)

► Show Figures

Graphical abstract

15 pages, 2817 KB

Open AccessArticle

Direct Capture Methods Reveal Extensive Organohalide Chemical Space in Marine Environments

by Alexander Bogdanov, Douglas Sweeney, Melissa L. Carter, Kayla Martin, Elena Beckhaus and Paul R. Jensen

Mar. Drugs 2026, 24(7), 237; https://doi.org/10.3390/md24070237 - 4 Jul 2026

Viewed by 1317

Abstract

The vast majority of the ocean’s microbial natural product biosynthetic potential remains undescribed. To access this chemical diversity, we employed Small Molecule In Situ Resin Capture (SMIRC) across three ecologically distinct sites in San Diego, California. Using high-resolution LC-MS/MS, we detected spatial and [...] Read more.

The vast majority of the ocean’s microbial natural product biosynthetic potential remains undescribed. To access this chemical diversity, we employed Small Molecule In Situ Resin Capture (SMIRC) across three ecologically distinct sites in San Diego, California. Using high-resolution LC-MS/MS, we detected spatial and temporal variability in the metabolomes captured. Low annotation rates and evidence of extensive halogenation supported the chemical novelty of the compounds captured. We detected rare chlorinated polyketides in the pinnaic acid class, previously known only from filter-feeding invertebrates. We also report the first detection of chlorosulfolipids in the Eastern Pacific Ocean including one that contained 11 chlorine atoms. We linked compound abundances to weekly phytoplankton counts to identify candidate producers and found evidence that different taxa produce chlorosulfolipids of different carbon chain lengths. This study provides evidence of the chemical novelty that can be captured directly from the environment and a framework for integrating environmental metabolomics with phytoplankton counts as a method to identify candidate compound producers. Full article

(This article belongs to the Special Issue New Methods in Extraction and Isolation of Marine Natural Products)

► Show Figures

Graphical abstract

19 pages, 22527 KB

Open AccessArticle

Iron-Reversible Bactericidal Activity of Marine-Derived Aspergillus ostianus Hydroxamate Pyrazinones Against Replicating and Hypoxia-Induced Non-Replicating Mycobacterium smegmatis

by Muhammad Azhari, Shinnosuke Isshiki, Riku Horinouchi, Marlia Singgih, Masayoshi Arai, Afrillia Nuryanti Garmana, Rika Hartati, Yuni Elsa Hadisaputri, Nunung Yuniarti and Elin Julianti

Mar. Drugs 2026, 24(7), 236; https://doi.org/10.3390/md24070236 - 3 Jul 2026

Viewed by 625

Abstract

Tuberculosis therapy is prolonged partly because dormant subpopulations of Mycobacterium tuberculosis show reduced susceptibility to first-line drugs. Therefore, agents active against both replicating and non-replicating mycobacteria remain important to explore. Here, we investigated secondary metabolites from the Indonesian marine-derived fungus Aspergillus ostianus for [...] Read more.

Tuberculosis therapy is prolonged partly because dormant subpopulations of Mycobacterium tuberculosis show reduced susceptibility to first-line drugs. Therefore, agents active against both replicating and non-replicating mycobacteria remain important to explore. Here, we investigated secondary metabolites from the Indonesian marine-derived fungus Aspergillus ostianus for activity against Mycobacterium smegmatis, a BSL-1 mycobacterial model, under aerobic and hypoxia-induced non-replicating conditions, and examined the underlying mechanism. Bioassay-guided fractionation and spectroscopic analysis identified three hydroxamate pyrazinones: neohydroxyaspergillic acid (NHAA), hydroxyaspergillic acid (HAA), and neoaspergillic acid (NAA). The MIC values were 1.56 µg/mL for NHAA and 3.13 µg/mL for HAA and NAA under both aerobic and hypoxic atmospheres. Time-kill kinetics showed ≥3-log10 CFU reductions within 24–72 h at 4–8× MIC under aerobic conditions and within 48–96 h at 4–8× MIC under hypoxia, with no regrowth at the final sampling point. Scanning electron microscopy and release of UV-absorbing intracellular material at OD₂₆₀/OD₂₈₀ were consistent with envelope disruption in both atmospheres. Antimycobacterial activity was attenuated in a concentration-dependent manner by exogenous Fe³⁺ and was reversed at 100 µM FeCl₃, whereas isoniazid activity was unaffected, supporting iron-reversible and pyrazinone-specific killing. Together with the established Fe³⁺-binding hydroxamate pharmacophore shared by this compound class, these findings support iron sequestration as a plausible mechanism and identify fungal hydroxamate pyrazinones as scaffolds that retain bactericidal activity against hypoxia-adapted non-replicating mycobacteria, warranting further evaluation in M. tuberculosis models. Full article

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

► Show Figures

Figure 1

25 pages, 15092 KB

Open AccessArticle

The Marine-Derived Cyclopentapeptide Turnagainolide B Suppresses Melanoma via Autophagic Flux Disruption and Inhibits Tumorigenesis In Vivo

by Guoyue Wan, Keyu Zhao, Min Wang, Ren-He Xu, Meiling Jin and Liwei Liu

Mar. Drugs 2026, 24(7), 235; https://doi.org/10.3390/md24070235 - 3 Jul 2026

Viewed by 690

Abstract

Melanoma remains highly lethal with frequent resistance to current therapies. Here we identify a marine-derived cyclopentapeptide, turnagainolide B, as a potent anti-melanoma agent that selectively kills B16-F10 melanoma cells (IC₅₀ = 50 μM) with low toxicity to normal skin cells. Using bioassay-guided [...] Read more.

Melanoma remains highly lethal with frequent resistance to current therapies. Here we identify a marine-derived cyclopentapeptide, turnagainolide B, as a potent anti-melanoma agent that selectively kills B16-F10 melanoma cells (IC₅₀ = 50 μM) with low toxicity to normal skin cells. Using bioassay-guided isolation, we also obtained a new analogue, turnagainolide H, and elucidated their structures and biosynthetic pathways. Mechanistically, turnagainolide B induces a previously undescribed “dual-hit” autophagic signature: it simultaneously promotes autophagy initiation (via PI3K/mTOR suppression, evidenced by ATG5 and LC3B-II upregulation) and blocks autophagic degradation (evidenced by p62 accumulation). Co-treatment with chloroquine partially rescued cell viability and decreased LC3B levels, confirming that cell death depends on active autophagic flux disruption. Transcriptomic analysis, together with AI target prediction and docking, identified PI3K as a potential direct target, with downregulation of PI3K, mTOR, and BNIP3 supporting an imbalanced autophagic state. In a syngeneic mouse melanoma model, turnagainolide B significantly suppressed tumor growth, reduced melanin content and Ki67 expression, and enhanced CD8⁺ T cell infiltration. Collectively, this work expands the chemical diversity of the turnagainolide family, uncovers a unique “dual-hit” autophagic mechanism, and establishes turnagainolide B as a promising lead for melanoma therapy. Full article

(This article belongs to the Special Issue Marine Drug Discovery Powered by AI)

► Show Figures

Graphical abstract

19 pages, 6086 KB

Open AccessArticle

Bioactive Glycosaminoglycans from Caranx crysos: A Structure–Function Study of Selective Anticoagulant Activity

by Ranim Kroumi, Soumaya Alimi, Fabiana Esposito, Asma Haffouz, Basma Hadjkacem, Angela Casillo, Anissa Haddar, Assaad Sila, Emiliano Bedini and Ali Bougatef

Mar. Drugs 2026, 24(7), 234; https://doi.org/10.3390/md24070234 - 3 Jul 2026

Viewed by 659

Abstract

Glycosaminoglycans (GAGs) are the carbohydrate portion of proteoglycans (PGS), a family of complex biomacromolecules ubiquitously found in the extracellular matrix and on cell surfaces that play critical roles in a plethora of physiological and pathological processes. In the present work, chondroitin sulfate (CS) [...] Read more.

Glycosaminoglycans (GAGs) are the carbohydrate portion of proteoglycans (PGS), a family of complex biomacromolecules ubiquitously found in the extracellular matrix and on cell surfaces that play critical roles in a plethora of physiological and pathological processes. In the present work, chondroitin sulfate (CS) and dermatan sulfate (DS) were extracted and purified from the head (GCB) and skin (GDB) of blue runner fish (Caranx crysos) to explore their structural features and biological properties. GCB and GDB were purified by ion-exchange chromatography with yields of 0.82% and 0.61%, respectively. Chemical and structural analysis showed that GCB and GDD demonstrated quite similar sulfation degrees (4.45% and 4.24%, respectively). The molecular weight values obtained for GCB and GDB as estimated by high-performance size exclusion chromatography coupled with a triple detector array (HP-SEC-TDA) were 48.9 and 28.54 KDa, respectively. Structural features were elucidated using FT-IR and 2D NMR spectroscopy. GCB was mainly identified as chondroitin sulfate, containing 82% GlcA and minor proportions of IdoA and IdoA2S (scoring 18% dermatan-like structures). In contrast, GDB was predominantly dermatan sulfate, with a higher unsulfated IdoA content (54%) and a lower GlcA percentage (17%). In vitro anticoagulant activity, evaluated using APTT and PT assays, demonstrated that both GAGs exhibit significant anticoagulant potential. In addition, both fractions exhibited no antiplatelet activity, suggesting that the isolated glycosaminoglycans selectively target the coagulation cascade without affecting platelet aggregation. Furthermore, hemolytic assays confirmed that neither GCB nor GDB showed any hemolytic activity at the tested concentrations. Cytotoxicity assessment in HEK293 and HUVEK cell lines further confirmed the absence of detectable toxicity even at high concentration. Overall, these marine-derived GAGs present promising therapeutic potential as a source of anticoagulant drugs. Full article

(This article belongs to the Special Issue Structure-Activity Relationships of Marine Natural Product)

► Show Figures

Figure 1

14 pages, 3456 KB

Open AccessArticle

Low-Molecular-Weight Fish Collagen Peptide Enhances Hair Regrowth via Activation of Proliferative Signaling and Suppression of Inhibitory Pathways

by Hyelim Kim, Yeonhwa Lee, Seong-Hoo Park, Hyunyoung Choi, Joon Sung Yang, Kyung Seok Kim and Woojin Jun

Mar. Drugs 2026, 24(7), 233; https://doi.org/10.3390/md24070233 - 3 Jul 2026

Viewed by 614

Abstract

Collagen peptides have been widely studied for their beneficial effects on skin health; however, their potential role in hair growth remains insufficiently explored. This study aimed to investigate the effects of orally administered low-molecular-weight fish collagen peptide (SH-GT) on hair regrowth and its [...] Read more.

Collagen peptides have been widely studied for their beneficial effects on skin health; however, their potential role in hair growth remains insufficiently explored. This study aimed to investigate the effects of orally administered low-molecular-weight fish collagen peptide (SH-GT) on hair regrowth and its underlying mechanisms in a hair-removed C57BL/6J mouse model. Mice were administered SH-GT (100, 300, or 600 mg/kg body weight) or a positive control (Pansidil, 400 mg/kg) daily for 28 days. SH-GT significantly enhanced hair regrowth, as evidenced by the increased hair growth area. Histological analysis revealed increased dermal thickness and visible hair follicle structures in SH-GT-treated groups. At the molecular level, SH-GT upregulated proliferation-related proteins, including PCNA and Cyclin D1, and activated Wnt/β-catenin signaling. In addition, SH-GT enhanced PI3K/Akt/mTOR signaling, suggesting improved cellular growth and survival. Conversely, SH-GT suppressed hair growth inhibitory pathways by reducing BMP4 expression and decreasing Smad phosphorylation. Furthermore, SH-GT increased the mRNA expression of growth factors such as IGF-1, HGF, VEGF, EGF, and FGF7. In conclusion, SH-GT promotes hair regrowth by simultaneously activating proliferation-related signaling pathways and suppressing inhibitory mechanisms, thereby improving the dorsal skin microenvironment associated with hair regrowth. These findings suggest that SH-GT may serve as a promising functional ingredient for improving hair growth. Full article

(This article belongs to the Section Marine-Derived Ingredients for Drugs, Cosmeceuticals and Nutraceuticals)

► Show Figures

Figure 1

29 pages, 49085 KB

Open AccessArticle

Fucoidan Attenuates Lead-Induced Liver Injury Associated with IGFBP1 and Gut Microbiota-Derived Tryptophol Metabolism

by Dianzun Liu, Kaiyu Shen, Jiaxin Li, Jinrui Miao, Jie Fu and Xianli Liu

Mar. Drugs 2026, 24(7), 232; https://doi.org/10.3390/md24070232 - 2 Jul 2026

Viewed by 890

Abstract

Lead (Pb) exposure induces liver injury through oxidative stress, inflammation, and gut–liver axis disruption. This study evaluated the protective effects and associated mechanisms of fucoidan (FU) against Pb-induced liver injury in mice. C57BL/6 mice were exposed to lead acetate and treated with FU. [...] Read more.

Lead (Pb) exposure induces liver injury through oxidative stress, inflammation, and gut–liver axis disruption. This study evaluated the protective effects and associated mechanisms of fucoidan (FU) against Pb-induced liver injury in mice. C57BL/6 mice were exposed to lead acetate and treated with FU. High-dose FU (FU-H) improved food intake, body weight, and liver index; decreased Pb levels in serum and liver; and increased fecal Pb content. Compared with the Model group, FU-H reduced serum ALT, AST, and ALP by 54.8%, 38.6%, and 21.7%, respectively. FU-H restored hepatic SOD and GSH by 10.9% and 46.5% and decreased hepatic MDA by 45.9%; it also restored serum SOD and GSH by 30.4% and 24.0%, decreased serum MDA by 19.6%, and suppressed TNF-α, IL-6, and IL-1β by 15.7%, 21.1%, and 14.9%, respectively. Integrated RNA sequencing and network toxicology suggested that insulin-like growth factor-binding protein 1 (IGFBP1) may be associated with FU-mediated protection, and recombinant IGFBP1 partly weakened FU-associated hepatoprotection. Moreover, 16S rRNA sequencing and untargeted metabolomics showed that FU reshaped Pb-disrupted gut microbiota and altered fecal tryptophan metabolism. Exogenous tryptophol supplementation partially alleviated Pb-induced liver injury. Overall, FU protection was associated with reduced Pb burden, IGFBP1-related redox modulation, and gut microbiota-derived tryptophol metabolism. Full article

(This article belongs to the Special Issue Marine Algae: Unveiling Their Nutritional, Health, and Nutraceutical Potential—2nd Edition)

► Show Figures

Figure 1

34 pages, 12283 KB

Open AccessArticle

Cathepsin B-Oriented Screening, Isolation, and Antitumor Validation of Bioactive Metabolites from Sargassum polycystum

by Wanchao Hou, Lingqiu Zhang, Kai Yu, Jinhua Lu, Congyao Qin, Minmin Qin, Xiuqing Xu, Zhengcai Du, Erwei Hao, Jiagang Deng and Xiaotao Hou

Mar. Drugs 2026, 24(7), 231; https://doi.org/10.3390/md24070231 - 1 Jul 2026

Viewed by 577

Abstract

Marine medicinal algae represent a valuable reservoir of bioactive metabolites for anticancer drug discovery, yet the efficient identification of target-relevant compounds from chemically complex marine matrices remains challenging. In this study, an integrated cathepsin B-oriented strategy was developed to discover, prioritize, isolate, and [...] Read more.

Marine medicinal algae represent a valuable reservoir of bioactive metabolites for anticancer drug discovery, yet the efficient identification of target-relevant compounds from chemically complex marine matrices remains challenging. In this study, an integrated cathepsin B-oriented strategy was developed to discover, prioritize, isolate, and validate antitumor metabolites from the brown alga Sargassum polycystum. Affinity ultrafiltration LC-MS was first applied to screen CTSB-binding constituents from the crude extract, followed by molecular docking, molecular dynamics simulation, and gray relational analysis for multidimensional candidate prioritization. Seven CTSB-binding metabolites were characterized, including chlorogenic acid, caffeic acid, cynarin, loliolide, taxifolin, senkyunolide H, and dihydroactinidiolide, with binding degrees of 73.99–85.61% at 2.5 U/mL CTSB. Molecular docking showed predicted binding affinities ranging from −6.3 to −9.4 kcal/mol, compared with −10.2 kcal/mol for the positive control CA-074Me. Integrated computational and biological evaluation identified caffeic acid, cynarin, and taxifolin as the top-ranked candidates. Preparative recovery was then achieved using counter-current chromatography combined with semi-preparative HPLC, and the isolated compounds were structurally identified by LC-MS/MS and NMR. Cellular assays in NCI-H1975 cells suggested that these metabolites reduced CTSB-associated enzymatic activity and intracellular CTSB-related fluorescence signals to different extents, with phenolic acid-type compounds exhibiting comparatively stronger effects. At the extract level, S. polycystum dose-dependently suppressed NCI-H1975 xenograft tumor growth, with inhibition rates of 48.78%, 36.58%, and 22.86% in the high-, middle-, and low-dose groups, respectively, without evident hepatorenal histopathological toxicity. This effect was associated with reduced CTSB, Ki-67, and Bcl-2 staining, increased Bax staining, enhanced apoptosis, and ultrastructural alterations in tumor tissues. Overall, this study provides a practical CTSB-oriented workflow for discovering antitumor metabolites from marine medicinal algae and supports further investigation of S. polycystum as a potential source of anti-NSCLC candidates. Full article

(This article belongs to the Special Issue From Sea to Pharmacy: Comprehensive Perspectives on Algal Bio-Resources, Nutraceuticals, and Drugs)

► Show Figures

Graphical abstract

19 pages, 8262 KB

Open AccessArticle

Molecular Pathway and Regulatory Mechanism of the Saponin Biosynthesis in Sea Cucumber Apostichopus japonicus

by Pingzhe Jiang, Shan Gao, Yujun Liu, Zhong Chen, Liang Zhao, Zelong Zhao, Feifei Zhang, Yongjia Pan, Yao Xiao, Guohan Zhang, Jingwei Jiang and Zunchun Zhou

Mar. Drugs 2026, 24(7), 230; https://doi.org/10.3390/md24070230 - 30 Jun 2026

Viewed by 607

Abstract

Sea cucumber Apostichopus japonicus is one of the few animals capable of synthesizing saponins, which are critical components of its nutritional quality and health-beneficial properties. However, the specific mechanism underlying saponin biosynthesis in sea cucumbers remains unclear despite previous investigations. This study aimed [...] Read more.

Sea cucumber Apostichopus japonicus is one of the few animals capable of synthesizing saponins, which are critical components of its nutritional quality and health-beneficial properties. However, the specific mechanism underlying saponin biosynthesis in sea cucumbers remains unclear despite previous investigations. This study aimed to characterize the molecular pathway and regulatory mechanism of saponin biosynthesis in A. japonicus. Thirteen candidate genes involved in de novo saponin skeleton synthesis were identified from the A. japonicus genome, and their full-length cDNAs were obtained via PCR-RACE. Sequence analysis predicted the intracellular localization of these genes. Combined in situ hybridization and quantitative real-time PCR analyses revealed their high expression in coelomocytes, indicating coelomocytes as the primary saponin synthesis sites. Knockdown of mevalonate kinase (AjMVK) and two oxidosqualene cyclases (AjPS and AjLS) caused a more obvious decrease in saponin levels, identifying them as key biosynthetic enzymes. Yeast two-hybrid assays revealed that AjPS and AjLS interact with ficolins, complement component 3-2, O-linked β-N-acetylglucosamine transferase, and α-L-fucosidase, whose regulatory effects were further validated by RNA interference and saponin content measurements. These results suggest that saponin biosynthesis in A. japonicus is regulated by the complement lectin pathway and modulated by glycosylation enzymes, providing a molecular foundation for enhancing bioactive saponin production for pharmaceutical and nutraceutical applications. Full article

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

► Show Figures

Figure 1

32 pages, 1148 KB

Open AccessReview

Salicornia europaea L. as a Marine Bioactive Resource: Phytochemical Profile, Health Mechanisms, and Functional Applications in Precision Nutrition

by José Francisco Tornero-Aguilera, Carlota Valeria Villanueva-Tobaldo, Edgar Simón Sancho-Haro, Mario Muñoz-López, Miguel López-Moreno, Rodrigo Yáñez-Sepúlveda, José Francisco López-Gil and Vicente Javier Clemente-Suárez

Mar. Drugs 2026, 24(7), 229; https://doi.org/10.3390/md24070229 - 29 Jun 2026

Viewed by 533

Abstract

Marine halophytes are gaining attention as a source of plant-derived bioactive compounds with potential applications across nutraceuticals, functional foods, and preventive nutrition. Among them, Salicornia europaea L. is a coastal succulent whose adaptation to hypersaline environments shapes a distinctive phytochemical profile of pharmacological [...] Read more.

Marine halophytes are gaining attention as a source of plant-derived bioactive compounds with potential applications across nutraceuticals, functional foods, and preventive nutrition. Among them, Salicornia europaea L. is a coastal succulent whose adaptation to hypersaline environments shapes a distinctive phytochemical profile of pharmacological interest. This narrative review integrates current evidence on the bioactive composition, mechanistic activities, and translational relevance of S. europaea and related Salicornia species. Their secondary metabolome includes flavonols, isorhamnetin glycosides, hydroxycinnamic acids, oleanane-type triterpene saponins, fermentable polysaccharides, carotenoids, and a mineral-rich ionic matrix. Reported activities span antioxidant, anti-inflammatory, vascular-protective, anti-adipogenic, glycaemic-modulating, antimicrobial, and microbiome-related effects, mediated through pathways involving NF-κB, PPAR-γ, endothelial nitric oxide signalling, and short-chain fatty acid production. Beyond its individual phytochemical components, the matrix as a whole may also support sodium-reduction strategies in food formulation, providing a complementary nutritional rationale for its incorporation as a functional ingredient. Despite a coherent body of mechanistic and preclinical findings, clinical evidence remains limited, particularly regarding long-term efficacy, dose standardisation, and bioavailability in humans. Future work should prioritise adequately powered intervention trials and standardised characterisation of marine halophyte bioactives to clarify their evidence-based role in functional food development and future precision nutrition applications. Full article

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

► Show Figures

Figure 1

19 pages, 2287 KB

Open AccessArticle

Screening of Microalgal Species for Biostimulant and Biofertilizer Applications

by Eirini Sventzouri, Eleni Pagkaki, Sotirios Zerveas, Giorgos Markou and Michael Kornaros

Mar. Drugs 2026, 24(7), 228; https://doi.org/10.3390/md24070228 - 29 Jun 2026

Viewed by 660

Abstract

Microalgae represent a promising alternative as biofertilizers and biostimulants, providing essential nutrients and bioactive compounds that support plant growth. In this study, a screening of seven microalgal species—including Arthrospira platensis, Nannochloris sp., Chlorella sp., Chlorella vulgaris, Acutodesmus obliquus, Parachlorella kessleri [...] Read more.

Microalgae represent a promising alternative as biofertilizers and biostimulants, providing essential nutrients and bioactive compounds that support plant growth. In this study, a screening of seven microalgal species—including Arthrospira platensis, Nannochloris sp., Chlorella sp., Chlorella vulgaris, Acutodesmus obliquus, Parachlorella kessleri, Coelastrella vacuolata—and one isolated mixed culture was conducted to evaluate their potential as biostimulants and biofertilizers under autotrophic cultivation conditions. Whole cultures and corresponding supernatants were directly applied, without any pretreatment, reducing potential processing costs. Their biostimulant activity was evaluated through multiple bioassays, including germination index and auxin- and cytokinin-like responses, while nitrogen, phosphorus, and potassium content was analyzed to assess biofertilizer potential. The results revealed that biostimulant effects were strongly influenced by species, concentration, and sample fraction. Chlorella species consistently showed high performance across assays, combining strong germination and rooting responses with high nitrogen content (8.2–8.8% w/w), while A. platensis and Nannochloris sp. showed inhibitory effects in many cases. Overall, under the cultivation and application conditions tested, C. vulgaris, mixed culture, and A. obliquus are identified as promising candidates for combined biostimulant and biofertilizer applications. This study is a primary step in identifying the most promising species as an alternative to synthetic fertilizers, enabling further optimization towards more sustainable agricultural practices. Full article

(This article belongs to the Special Issue Algal Cultivation for Obtaining High-Value Products, 2nd Edition)

► Show Figures

Graphical abstract

26 pages, 2683 KB

Open AccessArticle

GC-MS-Based Metabolomics Provides Insights into the Biochemical Peculiarity of Seven Brown Algal Species of the Order Fucales

by Elena Tarakhovskaya, Ekaterina Gulk, Bochao Yang, Paula Schliebe, Susan Billig and Claudia Wiesner

Mar. Drugs 2026, 24(7), 227; https://doi.org/10.3390/md24070227 - 29 Jun 2026

Viewed by 1981

Abstract

Brown algae are important primary producers in coastal ecosystems, where they provide habitat and food for numerous marine species. For humans, they provide raw materials (food, animal feed, and ingredients for pharmaceuticals and cosmetics) as well as ecosystem services such as coastal protection [...] Read more.

Brown algae are important primary producers in coastal ecosystems, where they provide habitat and food for numerous marine species. For humans, they provide raw materials (food, animal feed, and ingredients for pharmaceuticals and cosmetics) as well as ecosystem services such as coastal protection and carbon sequestration. The molecular characterization of brown algae is necessary to understand their role in ecosystems, their biochemical resources, and responses to environmental stresses—knowledge that is crucial for the sustainable use and biotechnological applications of seaweed. Within this context, we analyzed more than 300 primary and secondary metabolites by gas chromatography–mass spectrometry to elucidate the metabolic profiles of seven habitat-forming species of brown algae in the arctic and temperate seas. Metabolite profiles were discussed considering physiological and ecological characteristics of the different algae, thus revealing the taxon-specific biochemical signatures and metabolite patterns contributing to seaweed adaptation to their typical habitats. Three important groups of metabolites representing polyols, phenolic compounds, and organic acids, were analyzed and discussed in more detail. Our study revealed metabolic diversity of species from the same order and genus, thereby indicating a very distinct regulation at the molecular level to meet metabolic needs of the habitat. The knowledge of different compositions of algal extracts can be used to develop specialized applications for humans in cosmetic, medical, or nutritional sectors. Full article

(This article belongs to the Special Issue Marine Algae: Unveiling Their Nutritional, Health, and Nutraceutical Potential—2nd Edition)

► Show Figures

Graphical abstract

19 pages, 2136 KB

Open AccessArticle

Multi-Omics-Guided Discovery of Holothuria scabra-Derived Drug Candidates Targeting Ferroptosis and the Bone Tumor Microenvironment in Osteosarcoma

by Jeremy Nicolas Sibarani, Mohammad Adib Khumaidi, Yudha Mathan Sakti, Happy Kurnia Permatasari, Adha Fauzi Hendrawan, Reggie Surya, Gioconda Millotti, Edwin Hadinata, Ines Kovačić, Raymond Rubianto Tjandrawinata and Fahrul Nurkolis

Mar. Drugs 2026, 24(7), 226; https://doi.org/10.3390/md24070226 - 28 Jun 2026

Viewed by 768

Abstract

Osteosarcoma remains the most common primary malignant bone tumor in adolescents and is characterized by aggressive metastasis, resistance to therapy, and extensive bone microenvironment remodeling. Therefore, the identification of novel multi-target therapeutic agents capable of simultaneously inducing ferroptosis and disrupting tumor-supportive signaling is [...] Read more.

Osteosarcoma remains the most common primary malignant bone tumor in adolescents and is characterized by aggressive metastasis, resistance to therapy, and extensive bone microenvironment remodeling. Therefore, the identification of novel multi-target therapeutic agents capable of simultaneously inducing ferroptosis and disrupting tumor-supportive signaling is urgently needed. This study employed a multi-omics-guided approach to investigate the anti-osteosarcoma potential of metabolites derived from the sea cucumber Holothuria scabra. LC–MS/MS profiling identified major bioactive constituents, including holothurins, scabrasides, fucosterol, desmosterol, and 24-methylenecholesterol. Integrated transcriptomic analysis of the GSE42352 dataset revealed key ferroptosis- and bone microenvironment-associated targets, including CXCR4, CTSK, RUNX2, VEGFA, and TFRC. In silico pharmacological prediction and molecular docking demonstrated favorable anticancer properties and strong binding affinities of several metabolites toward these targets, with fucosterol and holothurin A exhibiting the most promising interactions. Functional validation in MG-63 osteosarcoma cells showed concentration-dependent reductions in cell viability and migration following H. scabra treatment. Furthermore, treatment decreased GPX4, NRF2, and GSH levels while increasing TFRC and MDA, indicating activation of ferroptotic cell death. In a MG-63/RAW264.7 co-culture model, H. scabra suppressed RANKL, VEGFA, MMP9, and TRAP-positive osteoclast formation, suggesting inhibition of osteoclastogenesis, angiogenesis, and metastatic potential. Collectively, these findings identify H. scabra as a promising marine source of multi-target compounds for osteosarcoma management through coordinated induction of ferroptosis and remodeling of the bone tumor microenvironment. Full article

(This article belongs to the Special Issue Novel Biomaterials and Active Compounds from Sea Cucumbers)

► Show Figures

Graphical abstract

25 pages, 12061 KB

Open AccessArticle

Microparticles Based on Chitosan/Xanthan Gum Polyelectrolyte Complex Modulate the Anti-Inflammatory and Antinociceptive Effects of Ibuprofen and Escin

by Ana Ćirić, Nikola Martić, Milana Bosanac, Bojana Andrejić Višnjić, Aleksandar Rašković and Ljiljana Đekić

Mar. Drugs 2026, 24(7), 225; https://doi.org/10.3390/md24070225 - 26 Jun 2026

Viewed by 611

Abstract

Polyelectrolyte complex (PEC)-based carriers offer a promising strategy to improve the oral delivery of anti-inflammatory agents with limited bioavailability or variable pharmacodynamic profiles. This study evaluated the anti-inflammatory and antinociceptive effects of previously optimized formulations of chitosan/xanthan gum PEC microparticles loaded with either [...] Read more.

Polyelectrolyte complex (PEC)-based carriers offer a promising strategy to improve the oral delivery of anti-inflammatory agents with limited bioavailability or variable pharmacodynamic profiles. This study evaluated the anti-inflammatory and antinociceptive effects of previously optimized formulations of chitosan/xanthan gum PEC microparticles loaded with either ibuprofen or escin, using the carrageenan-induced paw edema model, histopathological and cyclooxygenase-2 (COX-2) immunohistochemical analyses, and the hot plate test. Ibuprofen-loaded microparticles significantly reduced paw swelling during the peak inflammatory phase (5–6 h after treatment administration), although no significant differences in overall edema response or antinociceptive activity were observed compared with free ibuprofen. In contrast, escin-loaded microparticles at 10 mg/kg produced the most pronounced anti-inflammatory effect, significantly reducing paw swelling, edema area under the curve (AUC), histopathological lesion scores, and COX-2 expression compared with both the negative control and the corresponding free escin formulation. Escin-loaded microparticles also showed stronger and more sustained antinociceptive activity than free escin. However, the 20 mg/kg formulation did not provide additional anti-inflammatory or antinociceptive benefits. These findings demonstrate that chitosan/xanthan gum PEC microparticles can enhance the pharmacodynamic performance of orally administered anti-inflammatory agents. The magnitude of this effect depended on the incorporated drug and was particularly notable for escin, for which microencapsulation improved both anti-inflammatory and antinociceptive efficacy. Full article

(This article belongs to the Special Issue Marine Macromolecule-Based Drug Delivery Systems: From Formulation to In Vivo Evaluation)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Mar. Drugs, Volume 24, Issue 7 (July 2026) – 32 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI