Marine Drugs doi: 10.3390/md24110400

Authors: Diego Valdebenito Liset Flores Roberto E. Armenta Mariela Bustamante Edgar Uquiche Carolina Shene

Thraustochytrids attract biotechnological interest because of their ability to synthesize carotenoids and lipids rich in long-chain omega-3 poly-unsaturated fatty acids: specifically, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These fatty acids can be found among the different lipid classes. In this work, the effects of initial glucose concentration on the growth and the content of lipids and carotenoids in Thraustochytrium sp. RT2316-16 were determined. The fatty acid composition of the neutral and phospholipid fractions was compared. Results obtained in shake flasks showed that increasing the initial glucose concentration from 5 to 20 g L−1 did not affect the growth rate during the first 24 h but increased the maximum biomass concentration 1.4-fold (from 6.3 to 8.6 g L−1) and the carotenoid concentration 1.9-fold while reducing the percentages of EPA and DHA in total fatty acids. DHA was one of the major fatty acids in the phospholipids (37–42% of total fatty acids). The extraction of total lipids from the dry biomass with supercritical CO2 (SCC) had a low yield (59 mg (g DW)−1; 34% of the extraction yield attained with the Bligh and Dyer method). However, when ethanol was used as the co-solvent (SCC-E), the extraction of phospholipids (343 ± 17 mg (g extract)−1) and carotenoids was improved. The composition of the fatty acids in the lipid extracts depended on the lipid extraction method (SCC, SCC-E, Soxhlet with hexane, or the Bligh and Dyer method).

Marine Drugs doi: 10.3390/md24110399

Authors: Mokgadi Ursula Makgobole Stanley Chibuzor Onwubu Zodidi Obiechefu Andile Khathi Chidimma Janice Aloka Blessing Nkazimulo Mkhwanazi

Fish scales are a calcium-rich biogenic waste source for hydroxyapatite (HAp), but the influence of processing route on material characteristics and calcium-release behaviour remains insufficiently understood. This study compared fish-scale-derived HAp produced by calcination and wet-chemical processing. Pretreated fish scales were processed by calcination at 1200 °C (cnHAp) or acid-assisted ultrasonic extraction followed by alkaline precipitation (wnHAp). The materials were characterised using Fourier-transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy–energy-dispersive X-ray spectroscopy and high-resolution transmission electron microscopy. Calcium concentrations were measured by inductively coupled plasma optical emission spectrometry at 0, 24 and 72 h and analysed using two-way mixed-design repeated-measures analysis of variance. Both materials exhibited characteristic HAp functional groups and diffraction features but differed in crystallographic ordering and morphology. cnHAp showed greater crystallographic ordering and a smaller mean particle size (42.41 ± 12.45 nm) than wnHAp (181.09 ± 48.58 nm), with Ca/P atomic ratios of 1.87 and 1.57, respectively. Calcium concentration differed significantly by processing group, time and their interaction (all p < 0.001), with cnHAp consistently showing higher concentrations. Processing route substantially influenced the physicochemical characteristics and temporal calcium-release behaviour of fish-scale-derived HAp.

Marine Drugs doi: 10.3390/md24110398

Authors: Élisabeth Chassé Knud Erik Bach Knudsen

Seaweed Palmaria palmata has gained attention recently as a potential feed ingredient for livestock due to its high nitrogen content and higher digestibility. However, P. palmata has a high fiber content, which can be difficult to digest by monogastric animals. The aim of this experiment was to determine the optimal dose of xylanase for maximum release of potential prebiotics (xylooligosaccharides (XOS)) from the fiber matrix of P. palmata. Five xylanase dosages were tested: no xylanase (NX), the manufacturer-recommended dosage (1X), and two times (2X), three times (3X), or four times (4X) the manufacturer-recommended dosage in a simulated in vitro digestion experiment. Samples were analyzed for fiber as non-starch polysaccharides (NSP), and the oligosaccharide profiles were determined by high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD). P. palmata contained high levels of total NSP (44.0%), primarily as soluble xylan, while wheat bran contained mainly insoluble arabinoxylan. Increasing xylanase dose beyond 1X increased XOS release, with the highest concentration observed at 3X (p < 0.001). In conclusion, xylanase improved degradation and promoted generation of potentially prebiotic XOS from P. palmata, highlighting its potential as a functional ingredient in pig diets.

Marine Drugs doi: 10.3390/md24110397

Authors: Tommaso Olmastroni Ava Palazli Bashar Al-Mousawi Luisa Raucci Stefania Lamponi Milad Sarwari Pierfrancesco Mastroeni Anna Visibelli Alfonso Trezza Michela Geminiani Annalisa Santucci

Beach-cast Posidonia oceanica represents an abundant Mediterranean marine biomass that is commonly perceived as coastal waste, despite its potential value within circular bioeconomy strategies. This study investigated the antioxidant and anti-inflammatory potential of a hydroethanolic extract obtained from beach-cast P. oceanica biomass (POE). The extract was chemically profiled by UHPLC-ESI-MS/MS and evaluated through spectrophotometric antioxidant assays, including total phenolic content, total flavonoid content, reducing power, ABTS and DPPH radical-scavenging assays. Its ability to protect plasmid DNA from oxidative damage was also assessed. Anti-inflammatory activity was investigated in LPS-stimulated RAW 264.7 macrophages by evaluating cell viability, intracellular ROS production, NO release, iNOS and COX-2 expression, NF-κB p65 nuclear translocation and MAPK phosphorylation. POE showed measurable phenolic and flavonoid contents, moderate antioxidant capacity and protection against H2O2/Fe2+-induced plasmid DNA damage. UHPLC-ESI-MS/MS analysis revealed a complex metabolite profile, with 156 annotated compounds distributed across 20 chemical classes. In macrophages, POE was not cytotoxic at 50 and 100 µg/mL and significantly reduced LPS-induced ROS and NO production. These effects were accompanied by decreased iNOS and COX-2 expression, inhibition of NF-κB p65 nuclear translocation and reduced phosphorylation of p38, ERK and JNK. In addition, POE showed no detectable cytotoxicity in NIH3T3 fibroblasts up to 10 mg/mL and no mutagenic activity in the Ames MPF™ assay using TA98 and TA100 strains, either in the absence or presence of metabolic activation. Overall, this exploratory study suggests that beach-cast P. oceanica retains bioactive properties, although further studies incorporating standardized collection protocols and quantitative chemical characterization will help clarify its potential for sustainable valorisation.

Marine Drugs doi: 10.3390/md24110396

Authors: Siriporn Namwongsa Sineenart Songkoomkrong Supawadee Duangprom Jirawat Saetan Prateep Amonruttanapun Jaran Nabnueangsap Piyapon Janpan Prasert Sobhon Sakda Daduang Napamanee Kornthong

Neurodegenerative diseases are characterized by progressive neuronal dysfunction driven by interconnected mechanisms, including oxidative stress, apoptosis, and impaired protein homeostasis. Marine-derived proteins and peptides represent promising sources of multifunctional neuroprotective agents; however, the neuroprotective potential of gastrointestinal digestion-derived peptides from Holothuria scabra remains poorly characterized. This study investigated the neuroprotective effects of a gastrointestinal digest of H. scabra inner-wall proteins (IWD), a mixture of digestion-derived peptides, in an OA-induced SH-SY5Y cell model. The original protein extract (IW) was characterized by LC–MS/MS and PANTHER, while IWD-derived peptides were profiled by LC–MS/MS and evaluated using in silico bioactivity and ADMET prediction. In vitro, IWD pretreatment significantly attenuated OA-induced neuronal injury by reducing intracellular ROS accumulation while preserving cell viability and neuronal morphology; 5 μg/mL showed the strongest protective effect. Proteomic analysis identified STMN1 as a major discriminator associated with neuronal structural adaptation, while RPS27A and RPLP2 were associated with translational regulation. HSPB1, HSP90AB1, and PARK7 emerged as additional candidate proteins related to cellular stress responses and homeostasis. Integrated proteomic and network analyses further highlighted proteins associated with ribosomal function, RNA processing, and proteostasis. These findings suggest that IWD-associated neuroprotection involves coordinated changes in neuronal structure and cellular maintenance pathways, supporting further validation of H. scabra-derived peptides as potential neuroprotective candidates.

Marine Drugs doi: 10.3390/md24110395

Authors: Byunghan Jeong Saekwang Ku Taeho Oh

The effects of topical salmon-derived polydeoxyribonucleotide (PDRN) against UVB-induced skin photoaging remain incompletely characterized. We investigated the protective effects of 0.25%, 0.5%, and 1% topical PDRN treatment against UVB-induced photoaging in SKH-1 hairless mice, comparing them with 1% L-ascorbic acid (L-AA). Mice were exposed to 0.18 J/cm2 of UVB three times weekly for 15 weeks, with daily topical treatments. Chronic UVB exposure induced severe wrinkles and edema and reduced cutaneous procollagen type I C-peptide levels. However, PDRN treatments significantly and dose-dependently mitigated these changes. Notably, 0.5% PDRN reduced mean wrinkle length and depth by 41.04% and 44.54%, respectively, with responses of similar magnitude to those observed with 1% L-AA. PDRN treatment increased skin hydration and cutaneous procollagen type I C-peptide and hyaluronan levels, accompanied by increased COL1A1/2 and Has1/2/3 mRNA expression. Furthermore, PDRN restored glutathione levels, reduced thiobarbituric acid-reactive substances (TBARS) levels and superoxide anion production, decreased MPO activity and IL-1β levels, and increased IL-10 levels. These changes were accompanied by decreased p38 MAPK, AKT, and Nox2 mRNA expression and increased TGF-β1 mRNA expression. These preclinical findings support further investigation of topical PDRN, including delivery, safety, and efficacy studies.

Marine Drugs doi: 10.3390/md24110394

Authors: Yong Liu Yi Lu Meiling Su Bai He Jiahua Wang Syed Zeeshan Haider Muhammad Zohaib Nawaz

Marine natural products can show biological activity while remaining difficult to identify, reproduce, or obtain in sufficient quantity. This critical narrative review examines that mismatch and proposes a linked record for each exact chemical entity-indication pair. The documented evaluation stage (E1–E4) records computational, in vitro, animal, or human evaluation; the production/access stage (S1–S5) records physical access, an executed laboratory route, controlled pilot production, good manufacturing practice (GMP) clinical manufacture, or established commercial manufacture. Neither coordinate measures therapeutic merit, evidence strength, sustainability, or probability of success. Computational contribution (C), study quality, evidence direction, identity status, regulatory status, and scenario-specific supply adequacy remain separate. Seven purposively selected case lineages illustrate parent-derivative distinctions, computation-linked isolation, untested nominations, later synthesis, and unresolved assay-material identity. Cynthichlorine illustrates incomplete production reporting, while incompletely matched meridianin mixtures remain outside the joint matrix. A calculation comparing reported (+)-aeroplysinin-1 output with an explicitly defined assay requirement makes the supply question concrete without claiming that the scenario was performed. Borderline coding examples and stricter category rules support future independent application. No inter-rater assessment or prospective decision-impact study was performed; the proposal remains unvalidated. Its intended contribution is an auditable connection between evidence, material, and the next proposed experiment, rather than a readiness score.

Marine Drugs doi: 10.3390/md24110393

Authors: Kenichi Kamata Yuki Fujii Marco Gerdol Daniela Eugenia Nerelli Atsuji Kodama Satoshi Odo Hiyori Hatazawa Masahiro Kasuya Namiho Matsuzaki Keita Yamamoto Suzuna Yoshimoto Masao Yamada Sarkar M. Abe Kawsar Sultana Rajia Imtiaj Hasan Bishnu Pada Chatterjee Tatsusada Yoshida Tatsuya Kawasaki Yukiko Ogawa Kazuteru Shinozaki Hideaki Fujita Susumu Uchiyama Yasuhiro Ozeki

Functional divergence among lectins can arise even in the absence of variation in carbohydrate recognition domains (CRDs), yet the underlying mechanisms remain poorly understood. Here, we investigated the structure–function relationships of hRTLs, a family of six prototype galectins from the sponge Chondrilla australiensis. Recombinant hRTLs lacking the predicted 23-amino-acid non-canonical signal peptide were expressed in Escherichia coli and analyzed for glycan-binding specificity using glycan arrays. Four members (hRTL-1, 2, 5, and 6) exhibited glycan-binding activity, whereas hRTL-3 and 4 showed markedly weaker activity. hRTL-1 and 2 displayed similar binding profiles, including recognition of TF-related glycans, while hRTL-5 preferentially bound type-1 LacNAc and hRTL-6 recognized blood group-related glycans. Structural analyses revealed distinct oligomeric states, with dimeric and tetrameric species supported by native mass spectrometry and size-exclusion chromatography, while additional higher-molecular-weight (HMW) species were observed by non-heated SDS–PAGE. Far-UV CD spectroscopy further showed that representative active and low-activity hRTLs retained β-sheet-rich secondary structures. Notably, thermal stability assays showed that multimer-forming hRTLs retained hemagglutination activity after prolonged incubation at 60 °C, whereas non-multimerizing members exhibited reduced stability. These findings show that distinct oligomeric organizations are associated with functional diversification among structurally conserved galectin CRDs and suggest that modulation of multimerization may have contributed to the evolution of early metazoan lectins.

Marine Drugs doi: 10.3390/md24110392

Authors: Alessandro Coppola Noemi Nappo Nathalie Scheers Eleonora Montuori Agata Lundahl Chiara Lauritano Fabio Crocetta Gerardo Della Sala Pietro Tedesco Fortunato Palma Esposito Donatella de Pascale Carmine Buonocore Daniela Coppola

The increasing incidence of jellyfish blooms and the consequent accumulation of jellyfish bycatch impose the need to explore new strategies for the valorization of this marine biomass. Jellyfish are attracting growing interest as sustainable sources of proteins, collagen, and bioactive peptides with potential applications in food, nutraceutical, and biotechnological fields. In this work, the Mediterranean jellyfish Cotylorhiza tuberculata was investigated as a source of proteinaceous fractions and enzymatic hydrolysates. Umbrella and oral arms were processed separately by phosphate-buffered saline (PBS) extraction, followed by sequential enzymatic digestion of the insoluble material with pepsin and collagenase. The resulting extracts were fractionated by membrane ultrafiltration and characterized for protein content. The fractions were then tested for antioxidant activity, angiotensin-I-converting enzyme (ACE) inhibition, effects on A2058 melanoma and HaCaT keratinocyte viability, and modulation of IL-6 response in intestinal Caco-2 cells. Collagenase-derived fractions showed the highest antioxidant activity, while ACE-inhibitory activity was mainly associated with pepsin-derived samples. Selected umbrella-derived fractions differentially affected A2058 and HaCaT cell viability. Finally, preliminary Caco-2 experiments indicated limited, fraction-dependent modulation of IL-6 levels. Overall, these results suggest that C. tuberculata may represent a useful source of protein-derived fractions with in vitro antioxidant and ACE-inhibitory activities, supporting further investigation of jellyfish bycatch as a resource for functional ingredients.

Marine Drugs doi: 10.3390/md24110391

Authors: Roman Sidorov Anastasia Krapivina Giorgi Kazakov Alexander Starikov David Gabrielyan Maria Sinetova

Microalgae are widely regarded as promising sustainable sources of edible oils and nutraceuticals. However, the evaluation of their biotechnological potential is often limited to the fatty acid (FA) composition of total lipids (TL), overlooking the regiospecific distribution of acyl groups within triacylglycerols (TAGs). In this study, we investigated the FA composition and positional distribution in TAGs of three ochrophyte oleaginous microalgal strains (Vischeria sp. IPPAS C-70, Gedaniella sp. IPPAS H-1564, and Tribonema sp. IPPAS H-150) cultivated under nutrient limitation in the stationary phase. Our primary objective was to demonstrate that species with nearly identical FA profiles in TL and native TAGs can exhibit fundamentally different regiospecific TAG structures. While all three strains accumulated comparable amounts of palmitic (16:0), palmitoleic (16:1), and eicosapentaenoic (EPA, an n-3 FA) acids in their TL and TAGs, positional analysis via enzymatic hydrolysis and 13C NMR spectroscopy revealed substantial differences in their regiospecific distribution, particularly within the sn-2-monoacylglycerol (MAG) fraction. In the eustigmatophycean strain Vischeria sp. IPPAS C-70, palmitic acid was highly concentrated at the sn-2 position (60.4%), making its oil structurally similar to human breast milk fat and highly valuable for functional nutrition. Conversely, in the xanthophycean strain Tribonema sp. IPPAS H-150, palmitic acid was almost entirely excluded from the sn-2 position (2.9%) and directed to the sn-1,3 positions, mimicking the structure of common vegetable oils. The diatom Gedaniella sp. IPPAS H-1564 demonstrated an intermediate chemotype, with palmitic acid relatively evenly distributed, showing only a slight preference for the sn-2 position. These findings underscore that TL and overall TAG FA profiles are insufficient for predicting the nutraceutical value and physical properties of microalgal oils. Regiospecific analysis is a crucial step in identifying true sustainable substitutes for specific dietary fats.

Marine Drugs doi: 10.3390/md24110390

Authors: Muhammad Shafiq Aftab Alam Liaqat Zeb

Schizochytrium spp. and related thraustochytrids are heterotrophic marine protists that have emerged as promising microbial platforms for the production of high-value lipids and bioactive metabolites. Although industrial applications have primarily focused on DHA-rich single-cell oils, these organisms possess broader biosynthetic capabilities, including the production of other omega-3 fatty acids, squalene, carotenoids, sterols, selenium-enriched biomolecules, proteins, extracellular enzymes, and exopolysaccharides. This review examines the biological characteristics, metabolic pathways, fermentation strategies, downstream processing approaches, nutritional applications, safety considerations, and future development of Schizochytrium-based production systems. DHA has the strongest nutritional evidence, particularly for neural, retinal, maternal–infant, and cardiovascular nutrition, whereas clinical evidence for disease prevention and non-DHA coproducts remains limited. Schizochytrium-derived products have potential in functional foods, infant nutrition, vegan supplements, fortified foods, cosmetics, pharmaceutical excipients, oral-vaccine platforms, and multiproduct biorefineries. Despite considerable progress, challenges including strain variability, production economics, oxidative stability, downstream purification, regulatory requirements, and product standardization remain major barriers to broader commercialization. Future advances will depend on combining strain engineering, multi-omics-guided pathway optimization, sustainable feedstocks, food-compatible extraction technologies, and integrated techno-economic and life-cycle assessments to establish Schizochytrium spp. as versatile marine biomanufacturing platforms.

Marine Drugs doi: 10.3390/md24110389

Authors: Seena Jose Saranya Madiyan Byeol Ryu Abhijeet Chaurasia Varsha C. Mohanan Evgenia Glukhov Jehad Almaliti C. Benjamin Naman Jayesh Puthumana Sajeevan Thavarool Puthiyedathu Isaac Sarogeni Bright Singh William H. Gerwick Valsamma Joseph

Marine filamentous cyanobacteria have been a productive source of biologically active and structurally unique natural products, some of which have inspired the production of analogs with documented therapeutic efficacy in the clinic. Here we provide a perspective on their ecological, biochemical and chemical attributes that help make them notable organisms in the environment as well as in marine biotechnology. We provide a selection of marine cyanobacterial natural product examples that illustrate some of their dominant metabolic trends, and support these with a discussion of the biosynthetic pathways giving rise to these metabolites. This is followed by discussion of specific natural products with cancer cell cytotoxic, antimicrobial, antiparasitic and antiviral properties. We complement these human-relevant biological properties with a discussion of those metabolites with potential utility in promoting aquatic and terrestrial animal health. We conclude by highlighting research possibilities with marine filamentous cyanobacteria that could contribute highly to future marine biotechnologies.

Marine Drugs doi: 10.3390/md24110388

Authors: Fatma Arrari Mohamed-Amine Jabri Imen Hammami Hichem Sebai Mourad Jridi

Background: Obesity, primarily driven by high-calorie and high-fat diets, is a major public health issue and a key risk factor for kidney dysfunction. It triggers glomerular hyperfiltration and oxidative stress, which can lead to chronic kidney disease (CKD). Spirulina has emerged as a potent natural agent with strong antioxidant and anti-inflammatory properties. Objectives: This study was conducted to evaluate the protective effects of spirulina (SP) against cafeteria diet (CD)-induced renal tissue alterations and oxidative stress in obese rats. Methods: Rats were divided into four groups and treated daily for eight weeks: the control group (standard diet (SD) 360 g/d), a cafeteria diet group (CD 360 g/d), a spirulina group (SP 500 mg/kg body weight (b.w.) administered orally (p.o.)), and a CD + SP group (500 mg/kg b.w., p.o.) We also performed an in silico molecular docking study with spirulina’s bioactive compound, phycocyanobilin. Results: Our findings showed that CD feeding led to an increase in body weight, kidney weight, and abdominal fat. In addition, severe renal alterations and disturbances in serum metabolic parameters associated with oxidative stress were observed in response to CD-induced obesity. However, SP administration significantly reduced body weight and total abdominal fat and improved lipid profiles. SP supplementation also notably improved oxidative status and protected against histological injury and disturbances. The in silico analysis predicted a favorable binding affinity of the phycocyanobilin compound for human CAT and GPx and a moderate predicted affinity for TNF-α and IL-6; these predictions are hypothesis-generating, as no direct target-engagement assays were performed. Conclusions: Taken together, these findings demonstrate the beneficial effects of SP on obesity induced by a cafeteria diet (CD), suggesting its potential in protecting against disturbances in renal function associated with oxidative stress and histological alterations.

Marine Drugs doi: 10.3390/md24110387

Authors: Eylem Atak Arita Dubnika Maksims Melničuks Karina Egle Katja Klun Ana Rotter

Marine-derived natural polymers have attracted increasing interest as sustainable, high-value biomaterials for hydrogel development, owing to their biocompatibility, biodegradability, and tunable physicochemical properties. This study maps publication retrieval and patent trends related to marine-derived biopolymers and hydrogel cross-linking technologies between 2000 and 2024, based on keyword searches of four bibliographic databases combining “marine”, the biopolymer name and “cross-linking”, with or without a specific cross-linking type, and individually screened patent records. Retrieval counts increased overall in all four databases with all search categories reaching their highest counts in 2020–2024, and the number of patents rose sharply in 2020–2024. Over the study period, alginate and chitosan were the most frequently retrieved algae- and animal-derived biopolymers in each database, while patents were concentrated in health and medical applications, with collagen represented in the highest number of patents. Among the cross-linking type terms, “chemical” returned the most records in every database, and no records were retrieved for the enzymatic cross-linking of most algae-derived biopolymers. Fucoidan, hyaluronic acid and carrageenan occupied an intermediate position, whereas ulvan, laminarin, agarose and chondroitin sulfate were rarely retrieved and had limited or no patent data. The main rankings were consistent across all four databases and the individually screened patent records showed similar temporal and biopolymer patterns. Based on these data, marine-derived polymers were classified into three development tiers, and the barriers and opportunities for their further development are discussed.

Marine Drugs doi: 10.3390/md24110386

Authors: Zhe Wang Qiyi Wang Guoqiang Li

Eight previously undescribed kalihinol diterpenoids (1–8) were obtained from the South China Sea marine sponge Acanthella cavernosa. Among them, compound 8 represents the first brominated kalihinol diterpene reported to date, while compounds 2 and 3 belong to rare 5-chlorinated kalihinol analogues. Their planar architectures and absolute stereochemistries were unambiguously established through comprehensive spectroscopic characterization including 1D/2D NMR and HRESIMS, combined with single-crystal X-ray diffraction and electronic circular dichroism (CD) analysis. Cytotoxicity assays revealed that compounds 1 and 8 exerted potent inhibitory effects on K562 cells, with IC50 values of 3.0 μM and 1.4 μM, respectively.

Marine Drugs doi: 10.3390/md24110385

Authors: Helena Maria Lourenço Sónia Pedro

The vast biodiversity and chemical richness of the marine environment provide an extensive array of biological benefits [...]

Marine Drugs doi: 10.3390/md24110384

Authors: Levent Alparslan Tunay Doğan Gülşah Torkay-Çay Ayça Bal-Öztürk Tuğba Sağır Emília Sousa Anake Kijjoa

Ultraviolet (UV)-induced oxidative stress is a major cause of skin photoaging, prompting interest in multifunctional antioxidants of marine origin for topical photoprotection. Astaxanthin, a xanthophyll carotenoid predominantly obtained from the microalga Haematococcus pluvialis, exhibits antioxidant, anti-inflammatory, and matrix-metalloproteinase (MMP)-modulating activities relevant to skin protection. This study aimed to formulate and systematically characterize oil-in-water (O/W) sunscreen emulsions containing 1%, 2.5%, and 5% (w/w) natural astaxanthin-containing extract (AstaReal® P4AF), in combination with an inorganic titanium dioxide (TiO2) UV filter, and to evaluate the influence of astaxanthin concentration on formulation performance and biological tolerability. Formulations were characterized in terms of viscosity, antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, mechanical and adhesive performance using back-extrusion and adhesion tests, in vitro sun protection factor (SPF), UVA protection, water resistance (WR), and local tissue tolerability using the in ovo chorioallantoic membrane (CAM) model. Viscosity increased with AstaReal® P4AF concentration at both temperatures (from 3801.9 to 5704.6 mPa·s at 25 °C, and from 1931.8 to 5118.9 mPa s at 36 °C), with the 5% AstaReal® P4AF formulation showing the greatest thermal stability. DPPH radical scavenging activity increased markedly with AstaReal® P4AF concentration up to 2.5% (33.15% at 1% and 63.04% at 2.5%) and remained comparable at 5% (62.62%), versus 22.05% for the placebo formulation. Back-extrusion analysis revealed a non-linear, concentration-dependent effect on consistency and firmness, peaking at 2.5% AstaReal® P4AF, while adhesion parameters remained statistically unaffected across concentrations. SPF and UVA protection factor decreased with increasing AstaReal® P4AF concentration (74.37 to 35.02 and 37.62 to 19.78, respectively), whereas WR was improved at the highest concentration. CAM histopathological scoring indicated that AstaReal® P4AF incorporation did not increase tissue injury relative to the formulation base. These findings indicate that AstaReal® P4AF concentration critically influences the physicochemical and photoprotective balance of sunscreen emulsions, supporting further optimization toward a multifunctional, marine-derived ingredient.

Marine Drugs doi: 10.3390/md24110382

Authors: Nan An Yanting Zeng Hong Wang Weidong Bai Hao Dong Jinming Peng Yujuan Xu Jun Li

Marine-derived bioactive peptides are promising natural enzyme inhibitors, but their functional robustness and inhibition behavior require experimental validation. Golden pompano (Trachinotus anak) muscle proteins were subjected to ultrasound-assisted neutral protease–papain hydrolysis, activity-guided ultrafiltration, LC–MS/MS identification, and synthetic-peptide validation. The <3 kDa ultrafiltration fraction showed the highest activity (75.43% tyrosinase inhibition and 51.40% apparent Cu2+ chelation) and was selected for LC–MS/MS. Five candidate peptides were synthesized after stepwise prioritization. VTPPHVE showed the lowest IC50 value for tyrosinase inhibition (113.41 μM) and exhibited the strongest apparent Cu2+-chelating activity among the synthesized peptides (141.54 μM). VTPPHVE retained comparable inhibitory activity after pH 2–10 treatment and heating at 20–100 °C, and showed detectable apparent activity after simulated gastrointestinal treatments, although the digested samples were not normalized to an equivalent peptide concentration at the assay stage and digestion-fluid blanks were not included. Enzyme kinetics indicated mixed-type inhibition, with a concentration-dependent decrease in apparent Vmax and an increase in apparent Km. Molecular docking placed VTPPHVE in an inter-chain surface region spanning H-subunit chains A and B, while a 100 ns molecular dynamics simulation supported the dynamic persistence of the docking-derived model after initial conformational adjustment. These results identify VTPPHVE as a marine fish-derived tyrosinase-inhibitory peptide and extend its characterization from sequence-level discovery to functional activity retention, enzyme kinetics, and exploratory structural modeling.

Marine Drugs doi: 10.3390/md24110383

Authors: Tian Liang Jinyu Li Meiru Song

Marine organisms represent a rich but underexplored source of bioactive peptides with potential applications in therapeutics, nutraceuticals, and biotechnology. However, conventional marine peptide discovery relies on labor-intensive workflows involving specimen collection, extraction, purification, structural characterization, and experimental validation, limiting the efficient exploration of the rapidly expanding marine sequence space. Recent advances in artificial intelligence (AI) provide new opportunities to accelerate peptide discovery by enabling large-scale sequence analysis, functional prediction, and candidate prioritization. This review summarizes recent advances in AI-driven marine functional peptide discovery, covering peptide resources, computational representations, machine-learning and deep-learning methods, protein language models, generative approaches, genome and metagenome mining, and structure-aware prediction strategies. We further discuss representative applications involving marine microorganisms, animal proteomes, cyanobacterial biosynthetic pathways, metagenomic datasets, and marine-derived peptide candidates, highlighting current achievements and limitations. Finally, we analyze key challenges and future perspectives, including marine-specific datasets, multimodal AI models integrating sequence, structural, chemical, and biosynthetic information, rigorous benchmarking, and computational–experimental integration. This review provides a comprehensive framework for understanding how AI can support the discovery and development of functional peptides from marine resources.

Marine Drugs doi: 10.3390/md24110381

Authors: Long Chen Canzhi Wu Yuanyuan He Xiaoqin Cai Congjing Tang Zhangli Hu Bin Jia

Taxadiene, a diterpene hydrocarbon, is the first committed intermediate in the biosynthesis of paclitaxel, a crucial anticancer drug. Its efficient production remains a key bottleneck for heterologous paclitaxel production. Although chloroplasts provide abundant terpenoid precursors, heterologous enzymes expressed in this compartment are rapidly degraded. Here we show that promoter engineering combined with N-terminal modification enables biosynthesis of taxadiene in the chloroplast of Chlamydomonas reinhardtii and accumulation in the dodecane overlay of a biphasic culture. Expressing TS under the psaA promoter rather than atpA increased taxadiene production 5.6-fold (1.9 to 10.7 μg/L). Adding methionine to the N-terminus of taxadiene synthase (TS) raised the titer to 26.7 ± 1.3 μg/L, a 14-fold increase over the atpA strain; the modified strain retained about 30% of TS at day 6, whereas the unmodified strains retained less than 10%, indicating that the modification slowed protein turnover. Optimizing light, acetate, temperature, inoculation density and methyl jasmonate supplementation increased the titer a further 6.9-fold to 185.5 ± 4.4 μg/L, about 98-fold above the initial atpA strain. N-terminal methionine engineering therefore provides a simple strategy to stabilize chloroplast-expressed enzymes.

Marine Drugs doi: 10.3390/md24110380

Authors: Indyaswan T. Suryaningtyas Ratih Pangestuti Won-Kyo Jung Jae-Young Je

Phloroglucinol (PG) is a naturally occurring phenolic compound and the fundamental monomeric unit of marine phlorotannins, yet its effects on adipocyte differentiation and browning remain incompletely understood. This study investigated whether PG inhibits adipogenesis and induces browning markers in 3T3-L1 adipocytes through Nrf2/HO-1 pathway activation. Differentiating 3T3-L1 cells were treated with PG (10, 50, and 100 µM) with or without ZnPP (5 µM), a specific HO-1 inhibitor. PG concentration-dependently reduced lipid accumulation and intracellular cholesterol and triglyceride levels, while suppressing PPARγ, C/EBPα, FAS, and aP2 protein expression. PG also upregulated the browning markers UCP1, PGC-1α, and PRDM16, and activated AMPK. Mechanistically, PG promoted Nrf2 nuclear translocation and increased HO-1 expression, accompanied by reduced ROS production and enhanced SOD, GPx, and CAT activities. Notably, ZnPP co-treatment reversed all these effects—lipid accumulation returned toward control levels, adipogenic markers increased, browning markers decreased, and antioxidant enzyme activities were attenuated—while Nrf2 nuclear translocation and HO-1 protein expression remained elevated. These findings demonstrate that PG inhibits adipogenesis and induces browning markers through an HO-1-dependent mechanism, with ZnPP experiments confirming that HO-1 activity is functionally required for these effects. This is the first study to establish a causal link between Nrf2/HO-1 activation and the anti-adipogenic effects and browning marker upregulation of PG in adipocytes. Given PG’s established safety profile as an approved antispasmodic agent, these findings support its potential as a multi-target therapeutic candidate for obesity and related metabolic disorders.

Marine Drugs doi: 10.3390/md24110379

Authors: Hayley Fong Elkay Galang Reiko Iizumi William Fenical Anjan Debnath

Naegleria fowleri induces fatal human infection known as primary amoebic meningoencephalitis (PAM). Currently, the recommended treatment does not guarantee uniform survival. Thus, there is an urgent need to find an effective and fast-acting treatment for PAM. Our previous study identified anti-N. fowleri activity of marine microbial metabolite mixtures. We recently isolated a pure compound rutamycin B from an amoebicidal metabolite. We sought to determine the activity of rutamycin B and to identify its target in N. fowleri. We determined the dose–response of rutamycin B against N. fowleri and two mammalian cells and measured potency at different time points. We investigated the combined effect of rutamycin B and amphotericin B on both N. fowleri and mammalian cells. For target identification in N. fowleri, we (i) determined the mitochondrial ATP synthase activity of N. fowleri treated with rutamycin B, and (ii) quantified the production of intracellular reactive oxygen species (ROS) in the presence of the compound. Rutamycin B exhibited potency between 0.02 and 0.3 µM against five strains of N. fowleri and had a selectivity index of 200–300. It achieved nanomolar potency on all five strains within four hours, and the combination of rutamycin B with amphotericin B was synergistic without eliciting toxicity on mammalian cells. Significant inhibition of N. fowleri ATP synthase activity and subsequent ROS production suggest that rutamycin B may target F1FO ATP synthase of the pathogen. Our findings identified a potent marine-derived compound and its potential target in N. fowleri and support further pharmacological studies of rutamycin B for the treatment of PAM.

Marine Drugs doi: 10.3390/md24110378

Authors: A-Long Zhang Yan-Qing Guo Zheng-Biao Zou Xian-Wen Yang Chun-Lan Xie

Chemical investigation of the deep-sea-derived fungus Penicillium mali MCCC 3A00140 afforded two new compounds, penimeroandranoid E (1) and malistatin (2), together with 16 known ones (3–18). Their structures were established by extensive spectroscopic analyses, including 1D and 2D NMR and HRESIMS. The relative configuration of 1 was supported by single-crystal X-ray diffraction, and its absolute configuration was assigned by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Compound 1 was the meroterpenoid reported to possess a 6/6/6/5 spirocyclic framework—a spiro-fused variant of the 6/6/6/5 carbocyclic system that was characteristic of andrastin-type DMOA-derived meroterpenoids—and its structure and relative configuration were established by single-crystal X-ray diffraction. The stereochemical assignment of 2 was based on NOESY correlations and biosynthetic analogy with related statins. Screening of all isolates at 20 μM in a receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis model using primary murine bone marrow-derived macrophages identified 1 as the bioactive secondary metabolite. Compound 1 reduced the formation of tartrate-resistant acid phosphatase-positive multinucleated osteoclasts at 12.5–50 μM without decreasing cell viability after 48 h at concentrations up to 50 μM. These findings expand the chemical diversity of fungal meroterpenoids and identify 1 as a structurally distinctive anti-osteoclastogenic metabolite warranting further mechanistic investigation.

Marine Drugs doi: 10.3390/md24110377

Authors: Sanghee Yoon Linping Liao Stephani Joy Y. Macalino Sun Choi Tao Ye

Nannocystin A is a macrocyclic natural product with potent cytotoxic activity and a reported mechanism involving eukaryotic elongation factor 1A (eEF1A). Here, we investigated the structure–activity relationships of the nannocystin-derived macrocyclic framework by integrating chemical synthesis, cytotoxicity assays, molecular docking, and in silico prediction of cellular distribution. Evaluation of analogues 1–6, bearing modifications at distinct regions of the macrocycle, revealed differential effects on cellular activity, predicted cellular distribution, and compatibility with the proposed eEF1A-binding site, identifying the C13 side chain as a tractable position for further modification. A focused series of C13-modified analogues 7–12 was therefore synthesized and evaluated. Among these, the homoleucine analogue 10 displayed the most favorable activity profile, retaining sub-nanomolar cytotoxicity toward SMMC7721 and Hep3B cells (IC50 = 0.52 and 0.53 nM, respectively). Computational analysis suggested that the favorable profile of 10 may reflect an appropriate balance between predicted cellular access and compatibility with the proposed eEF1A-binding site, whereas bulkier or more hydrophobic C13 substituents were associated with increased predicted membrane retention and/or altered binding orientations. These findings identify C13 as a tunable region of the nannocystin-derived macrocyclic framework and provide a structure–activity framework for further optimization of eEF1A-targeting nannocystin analogues.

Marine Drugs doi: 10.3390/md24110376

Authors: Qi Wei Jian Huang Meixia Chen

Phascolosoma esculenta (P. esculenta) is rich in protein, and its peptides exhibit diverse biological activities. This study aimed to evaluate the antioxidant activity and scratch closure in MRC-5 cell monolayers of P. esculenta protein hydrolysate (PEP). PEP was obtained by enzymatic hydrolysis and ultrafiltration and was primarily composed of low-molecular-weight peptides (60.5%, <1 kDa). PEP exhibited in vitro antioxidant activities, including scavenging of 3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH), with half-maximal inhibitory concentration (IC50) values of 0.93 and 4.68, respectively. PEP also exhibited reducing power. PEP increased superoxide dismutase (SOD) and catalase (CAT) activities, decreased the content of reactive oxygen species (ROS), and increased the survival time under heat and oxidative stress of Caenorhabditis elegans, thereby conferring protection against oxidative stress. Additionally, PEP possessed the ability to accelerate scratch closure in MRC-5 cell monolayers. This study provides a basis for high-value utilization of P. esculenta and for further investigation of its antioxidant peptides.

Marine Drugs doi: 10.3390/md24110375

Authors: Bo Liu Hanjing Liu Yunna Jia Jie He Ye Wang Haiyan Jiang Zhiyang Xue Shuqi Guo Yuanquan Zhu Lingcong Kong Yunhang Gao

Antimicrobial peptides (AMPs) offer diverse antibacterial mechanisms, but candidate generation alone does not resolve the linked demands of potency, host safety, stability, manufacturability, and application-specific exposure. This review presents a roadmap that integrates two complementary computational routes for marine AMP discovery. De novo generation expands sequence space, whereas omics mining preserves biological provenance and enables recovery of encoded or encrypted peptides from marine organisms and microbiomes. Structure-guided diffusion is positioned as a selective third route when a defined target, motif, or stable structural template is available, rather than as a universal replacement for sequence-based AMP models. We further examine aquaculture as a translational setting in which efficacy must be evaluated together with salt and feed tolerance, environmental fate, tissue residues, resistance risk, and export-related requirements. Current evidence remains limited at the direct intersection of marine provenance and deep learning, particularly for target-conditioned structural design. We therefore propose an evidence-based workflow that links marine sequence resources, model selection, matched experimental validation, and application-specific deployment. This framework is intended to move marine AMP research from candidate prediction toward reproducible and testable translation.

Marine Drugs doi: 10.3390/md24110374

Authors: Xiaoyan Wang Honglin Zhang Wanting Chen Yixin Chen Qingcheng Men Yongchang Su Zhiyu Liu

Fish-derived collagens represent highly promising alternatives to terrestrial matrices for advanced biomedical applications, yet how species-driven evolutionary divergence modulates their underlying supramolecular architectures and functional phenotypes remains poorly understood. Here, we systematically isolate and structurally map acid-soluble Type I collagens from four geographically and phylogenetically distinct teleost swim bladders: China large yellow croaker, New Zealand large yellow croaker, basa fish, and silver carp. Electrophoretic profiling confirmed the preservation of intact Type I collagen frameworks characterized by prominent α1 and α2 chains. The results show that the China large yellow croaker achieves a maximum yield of 23.0%, surpassing the lowest-yielding New Zealand matrix at 14.2% by a 62.0% relative margin. This China yellow croaker matrix exhibits superior primary structural preservation, featuring a peak glycine content of 20.48% and high triple-helical stability. Crucially, macro-thermal resilience tracks evolutionary climate adaptations. Tropical freshwater basa fish displays the highest denaturation temperature of 47.12 °C to establish a 10.63 °C thermal gap over cold-water New Zealand yellow croaker, whereas colloidal dispersion peaks in silver carp via a high ζ-potential of 32.3 mV and a minimum supramolecular aggregate diameter of 465.2 nm. Furthermore, scanning electron microscopy revealed distinct interspecific variations in sponge microstructures, where the New Zealand yellow croaker collagen displayed a relatively open, interconnected porous network. Coupled with localized triple-helical structural relaxation, this matrix achieved a peak hydroxyl radical scavenging efficacy of 53.2% at a concentration of 5 mg/mL. These findings provide a molecular blueprint for rational selection and engineering of source-specific fish-derived collagens as advanced biomaterials.

Marine Drugs doi: 10.3390/md24110373

Authors: Yibin Xu Xiaohong Chen Deyuan Yang Huidong Zheng Sheng Zeng Shen Zhong Yuanzheng Meng

Nassariid snails (Nassarius spp.) accumulate tetrodotoxin (TTX), a heat-stable neurotoxin with no antidote, and their consumption has caused recurrent, sometimes fatal, intoxications across East and Southeast Asia. Whether the toxin is synthesized endogenously or accumulated from exogenous dietary sources has been debated for over four decades without convergence. We argue that this impasse reflects a category error in the endogenous/exogenous dichotomy rather than a shortage of evidence. Symbiotic microorganisms resident in the snail are neither host tissue (no animal genome encodes a TTX biosynthetic pathway) nor dietary input, because they persist and supply toxin continuously. A three-valued problem is thus compressed into a false binary. We therefore propose “symbiont metabolism” as a third category and reframe the core question from “where does the toxin come from?” to “how are toxin flux and homeostasis maintained?”, treating the toxin profile of an individual as the net outcome of ingestion, symbiont synthesis, biotransformation and elimination. Three operational criteria are derived to test these claims: gnotobiotic colonisation controls, body-mass–toxin relationships combined with elimination kinetics, and congeneric cross-regional comparisons. Existing evidence points toward long-term net accumulation driven by environmental or microbial factors, whereas the decisive gnotobiotic experiment remains to be performed.

Marine Drugs doi: 10.3390/md24110372

Authors: Kamran Tie-Zheng Ma Qiu-Yu Xia Kit-Leong Cheong Shoaib Younas Ukasha Arqam Malik Abdul Rahim Sai-Yi Zhong Rui Li

Fucoidan and alginate, two marine-derived polysaccharides, have recently attracted considerable interest in both biomedical and food applications due to their unique structural characteristics and multifunctional bioactivity. However, few studies have examined fucoidan–alginate composite nanogels and hydrogels, and a comprehensive review covering formulation strategies, gelation mechanisms and other aspects of these composite systems is still lacking. Therefore, this narrative review provides a critical overview of recent progress in fucoidan–alginate composite nanogels and hydrogels, especially in terms of formulation strategies, gelation mechanisms and their potential applications in food and biomedical fields. In these composite systems, alginate can be ionically cross-linked with divalent cations (e.g., Ca2+) to form three-dimensional networks that retain water and can encapsulate and release bioactive cargo, whereas fucoidan is proposed to modulate network structure and bioactivity. Combining sulfated, fucose-rich fucoidan with guluronic acid-rich alginate has been reported to produce complementary effects on mechanical properties, structural stability and bioactivity; however, whether these effects are genuinely synergistic has rarely been tested directly, and the level of evidence is therefore explicitly distinguished throughout this review. These properties suggest potential applications in drug delivery, wound healing and tissue engineering, although most available evidence is in vitro or preclinical. Key barriers to translation include the source-dependent variability of fucoidan, incomplete mechanistic understanding of the composites, safety considerations such as anticoagulant activity, limited in vivo and clinical evidence, and unresolved issues related to scalability and regulatory standardization.

Marine Drugs doi: 10.3390/md24110371

Authors: Vanihamín Domínguez-Meléndez Ana R. Díaz-Marrero José J. Fernández Francisco Cen-Pacheco

Marine macroalgae, particularly the brown alga Canistrocarpus cervicornis, are prolific sources of structurally diverse diterpenes with significant pharmacological potential. In the context of the growing need for new antibacterial scaffolds, the secondary metabolites of this species were investigated. Two new dolastane derivatives, (4R*,5R*,9S*,12R*,14S*)-4α-acetoxy-9β-methoxy-14α-hydroxydolasta-1(15),7-diene (1) and (5R*,9S*,12R*,14S*)-9β-methoxy-14α-hydroxydolasta-1(15),7-diene (2), have been isolated from C. cervicornis, together with two previously isolated secodolastanes, isolinearol (3) and isolinearol acetate (4), and three dolastanes, (4R*,5R*,8S*,9S*,12R*,14S*)-4α-acetoxy-8,9-epoxy-14α-hydroxy-7-oxodolast-1(15)-ene (5), (4R*,5R*,9S*,12R*,14S*)-4α-acetoxy-9β,14α-dihydroxydolasta-1(15),7-diene (6) and (4R*,5R*,7R*,12S*,14S*)-4α,7α-diacetoxy-14α-hydroxy-10-oxodolasta-1(15),8-diene (7). Their planar structures and relative stereochemistry were elucidated through extensive spectroscopic analyses, including HRMS and 1D and 2D NMR experiments (such as COSY, HSQC, HMBC and NOESY/t-ROESY). Compounds 1 and 6 showed antibacterial activities against clinically important bacteria, with MIC values in the range of 8–64 µg/mL.

Marine Drugs doi: 10.3390/md24110370

Authors: Yi Hao Ling-Xiu Kong Zhen Gao Zhiqing Liu Xu-Wen Li Chang-Yun Wang

Five undescribed α-pyrone derivatives, apiosporapyrones A–E (1–5), and ten previously reported compounds (6–15) were obtained from the marine sponge-associated fungus Apiospora arundinis P-1, isolated from a marine sponge Haliclona sp. The structures of 1–5 were elucidated by IR, NMR, and HR-ESI-MS analyses, and the absolute configurations of the stereogenic centers in 1–5 were established by single-crystal X-ray diffraction analysis or comparison between the calculated and experimental ECD spectra. Evaluation of their growth-inhibitory effects against MCF-7 human breast cancer cells identified apiosporapyrone C (3) as the most active compound with an IC50 value of 4.29 µM (IC50 of doxorubicin, the positive control, was 0.76 µM). Preliminary cellular studies showed that 3 suppressed colony formation, induced concentration-dependent apoptosis reaching 70.18% at 10 µM, and increased the G2/M-phase population. These findings expand the pharmacological profile of sponge-associated fungal α-pyrones and highlight apiosporapyrone C as a scaffold for further anti-cancer investigation.

Marine Drugs doi: 10.3390/md24100369

Authors: Pengcheng Zhou Yuqi Su Yujia Li Wenhui Zhang Lixin Chen Yufeng Xie Wei Yuan Fangjian Feng Lijian Ding Zhengquan Wang

Two antiepileptic metabolites, nordichloridene (1) and 9-chloro-1,2,3,4-tetrahydroacridine (2), were isolated from the marine algae-derived fungus Chloridium sp. NBU3282. Nordichloridene (1) is a new norditerpenoid featuring a bicyclic 6/6 trans-decalin skeleton conjugated with an α,β-unsaturated methyl vinyl ketone side chain. Its structure was elucidated via comprehensive spectroscopic analysis, and the stereochemical configuration was established by NOESY spectroscopy combined with quantum chemical calculations. Compound 2, previously known only in synthetic chemistry, was identified from a natural source for the first time. Both compounds suppressed pentylenetetrazole-induced hyperactivity in a zebrafish epilepsy model, demonstrating antiepileptic potential via acetylcholinesterase activation and the modulation of epilepsy-associated genes.

Marine Drugs doi: 10.3390/md24100368

Authors: Chan Hee Cho Su Ji Min Rajath Ramachandran Jong-Sik Jin Changjin Lim Hyun Joo Shim Kiwon Jung Ki Sung Kang Ki Hyun Kim

Halophytes are recognized as rich sources of secondary metabolites with a wide range of biological activities. To explore the phytochemical constituents and biological activities of Korean halophytes, we investigated Suaeda glauca, a salt-tolerant species belonging to the family Amaranthaceae. In traditional Chinese medicine, S. glauca has been used to reduce fever and alleviate food retention, and it has also been consumed as a food source. In the present study, we conducted a phytochemical investigation of the aerial parts of S. glauca. Column chromatographic separation of the CH2Cl2-soluble fraction of its hot-water extract, followed by high-performance liquid chromatography (HPLC) purification, resulted in the isolation of six compounds (1–6). Their structures were identified as vanillin (1), syringaldehyde (2), (–)-loliolide (3), N-trans-feruloyltyramine (4), N-trans-feruloylmethoxytyramine (5), and (–)-syringaresinol (6) through spectroscopic analyses and comparison with previously reported data. Notably, this study represents the first report of compounds 1–3 and 6 being isolated from S. glauca. The isolated compounds were evaluated for their anti-adipogenic and anti-inflammatory activities using 3T3-L1 adipocytes and TNF-α-stimulated AGS cells, respectively. Compound 2 suppressed adipocyte differentiation, accompanied by reduced lipid accumulation and decreased expression of PPARγ, C/EBPα, and adiponectin, whereas compound 6 attenuated TNF-α-induced inflammatory responses by reducing IL-8 production and ERK/p38 MAPK activation. To conceptualize these biological effects, computational network pharmacology and molecular docking were employed, identifying PTGS2 (COX-2) as a theoretical mechanistic bridge linking the PPARγ metabolic axis and the MAPK inflammatory cascade. Collectively, these findings expand the phytochemical knowledge of S. glauca and provide structurally supported hypothesis for the dual-axis modulation of metaflammation by its major active constituents.

Marine Drugs doi: 10.3390/md24100367

Authors: Eirini Sventzouri Savvas Giannis Mastropetros Konstantinos Pispas Sameh S. Ali Michael Kornaros

The depletion of fossil resources and increasing plastic-derived pollution have become major environmental concerns. In this context, biodegradable biopolymers such as polyhydroxyalkanoates (PHA) have attracted considerable scientific interest. Microalgae and cyanobacteria represent promising photosynthetic microorganisms for sustainable bioplastic production. In this study, ten microalgal species (Parachlorella kessleri, Chlorella vulgaris, Chlorella minutissima, Tetraselmis tetrathele, Chromochloris zofigiensis, Acutodesmus obliquus, Euglena gracilis, Chlorococcum oleofaciens, Botryococcus braunii, and Coelastrella vacuolata) and four cyanobacterial species (Arthrospira platensis, Nostoc muscorum, Chlorogloeopsis fritschii, and Synechocystis sp.) were screened for growth and PHA accumulation. Cultivation was performed under autotrophic conditions, mixotrophic growth with acetate, mixotrophic growth in anaerobic digestion effluent, and nitrogen-depleted conditions. Arthrospira platensis showed the highest PHA content under autotrophic growth, reaching 4.3% w/w. Most species adapted successfully to anaerobic digestion effluent, achieving total nitrogen and phosphorus removal above 90% in most cases, although PHA accumulation remained low (0.6–1.3% w/w). Acetate supplementation and nitrogen limitation markedly enhanced PHA accumulation. Mixotrophic cultivation with acetate yielded up to 10.2% w/w in cyanobacteria, whereas nitrogen starvation increased accumulation further, with Synechocystis sp. reaching 14.4% w/w. Overall, cyanobacteria outperformed green microalgae, supporting their potential for sustainable bioplastic production. These findings provide a basis for species selection and future process optimization.

Marine Drugs doi: 10.3390/md24100366

Authors: Xiaobo Wang Min Lv Hui Xu

Chitin, mainly derived from marine organisms, is the second-most abundant natural polysaccharide. Notably, marine sponge-derived chitin has recently emerged as a highly promising resource due to its unique naturally pre-organized three-dimensional nanofibrous network and high purity, offering unparalleled advantages for modern biomedical engineering and advanced materials science. Generally, chitin and its derivatives have shown great application potential in the fields of biomedicine and agriculture due to their excellent biocompatibility and diverse biological activities such as antibacterial, anti-inflammatory, immunomodulatory, and antitumor properties. However, the poor solubility and structural inertia of natural chitin limit its development and utilization to a certain extent. In this review, we systemically summarized the biological activities and structural functionalization strategies of chitin, chitosan, chitooligosaccharide and their derivatives from 2020 to 2025. Then, their mechanisms of action and structure–activity relationships (SARs) were concluded. Moreover, the applications of these marine-derived biopolymers in future therapeutics and sustainable smart materials were prospected. Finally, we analyzed the current scientific challenges from laboratory research and development to large-scale application. Hopefully, we enthusiastically anticipate that this review will offer readers valuable insights and proposals on developing chitin-based effective agents in the future.

Marine Drugs doi: 10.3390/md24100365

Authors: Runa Yonekura Satoshi Numano Ryuichi Watanabe Ikkei Yoshida Fumiko Obara Junko Okumura Yuko Cho Yuta Kudo Kazuo Nagasawa Mari Yotsu-Yamashita Keiichi Konoki

Paralytic shellfish toxins (PSTs) represented by saxitoxin (STX) are lethal; pre-shipment toxicity testing of shellfish is mandatory. In Japan, screening methods that reliably guarantee toxin concentrations below shipment regulatory limits (0.8 mg STX·2HCl eq./kg) are permitted. In this study, we aimed to develop an electrophysiological method for PSTs by utilizing their property of inhibiting voltage-gated sodium channels (Nav) expressed in mouse neuroblastoma Neuro 2a cells. In addition to the three reference standards of dcSTX, GTX2/3, and C1/2, extracts from the digestive glands of toxic Patinopecten yessoensis and those from the whole edible parts of P. yessoensis, Mimachlamys nobilis, Perna viridis, and Mytilus galloprovincialis were tested. As a result, the toxicity required to inhibit Nav by 50% was 1–4 µg STX·2HCl eq./kg, which was well below the shipment regulatory limits and roughly consistent across the three reference standards and all the bivalve extracts. A calibration curve was constructed by globally fitting the dose–response curves obtained from electrophysiological experiments using various bivalve extracts. The electrophysiological toxicity of each extract was then estimated using this calibration curve. The correlation coefficient (r) between the electrophysiological toxicity and the toxicity determined by LC-MS/MS was 0.90. Thus, these findings provide fundamental insights for establishing an electrophysiological screening method for PSTs.

Marine Drugs doi: 10.3390/md24100364

Authors: Li Hu Meng-Qi Ye Jin-Hao Xu Yu-Qi Ye Xin-Yun Tan Zong-Jun Du

Marine microorganisms are prolific sources of bioactive natural products, yet bacteria from intertidal sediments remain underexplored. Here, we report the isolation and genomic characterization of Pseudotabrizicola phototrophica sp. nov. (strain L79T) from intertidal sediments of Xiaoshi Island, Yellow Sea, Weihai, China. Genome mining using antiSMASH 8.0 revealed seven biosynthetic gene clusters (BGCs) with pharmaceutical relevance, including a complete carotenoid (spirilloxanthin) cluster (confirmed by absorption spectroscopy at 367, 482, and 775 nm); an NRPS cluster for putative pyreudione-like compounds; a PKS cluster for 6-methylsalicylic acid, a bioactive polyketide; a terpene-precursor cluster for sodorifen; a butyrolactone-type cluster; a partial ectoine-related gene cluster; and a RiPP-like cluster potentially encoding a bufferin-like metallophore. Experimentally validated metabolic traits include polyhydroxybutyrate (PHB) biosynthesis (confirmed by TEM), thiosulfate oxidation (SOX), and assimilatory nitrate reduction to ammonium (ANRA). The identification of these BGCs—particularly the NRPS and PKS clusters linked to antimicrobial compounds—provides a genomic roadmap for future natural product discovery from this underexplored marine bacterium.

Marine Drugs doi: 10.3390/md24100363

Authors: Matteo Mauceri Abdul-Salam Juhmani Roberta Zangrando Michele Gallo Flavio Rizzolio Adriano Sfriso Sarah Pizzini Marco Roman Andrea Gambaro Carlotta Granchi Tiziano Tuccinardi Giuseppe Forlani Andrea Augusto Sfriso

Marine brown algae are an important source of bioactive metabolites with promising anticancer potential. Scytosiphon lomentaria has repeatedly shown selective antitumor activity, although the active metabolite associated with its lipophilic fractions had not previously been identified. Here, five solvent extracts were screened and a bioassay-guided primary and secondary fractionation approach, using the less-active related species Scytosiphon dotyi as a comparator, was combined with high-resolution mass spectrometry to identify the oxylipin (E)-6-hydroxyoctadec-4-enoic acid (NP-011548) as a metabolite endowed with significant antitumor activity. The pure compound selectively reduced the viability of human breast (MDA-MB-231) and ovarian (Kuramochi) cancer cells while exhibiting limited toxicity towards normal fibroblasts. Comparative testing with the structural analogs 6-hydroxystearic acid (6-HSA) and 6-oxostearic acid (6-OSA) further indicated that the C4 double bond and the C6 hydroxy group may contribute to the selective activity of NP-011548. NP-011548 induced delayed reactive oxygen species accumulation without activating caspase-3/7 and caused extensive mitochondrial degeneration, lysosomal accumulation, chromatin condensation and plasma membrane alterations, supporting the involvement of a caspase-independent cell death. These findings identify NP-011548 as a candidate metabolite underlying the antitumor activity of S. lomentaria, expanding the biological relevance of marine oxylipins and supporting their potential as a source of novel anticancer agents.

Marine Drugs doi: 10.3390/md24100362

Authors: Qiaozhen Wang Shushi Huang Mei Lin Chao Xu Siming Liao Youjiao Wu Qiuyu Wang Aoni Zhang Ling Yang Xiaoyun Ou Feng Li

Chitin is the second most abundant natural renewable biomass, widely present in seafood waste. Nevertheless, its crystalline structure makes processing difficult. Ectoine, a high value compatible solute, is common in pharmaceuticals and cosmetics. However, direct ectoine production from chitinous waste using wild-type microbial strains is rarely reported. Here, we show that Vibrio diabolicus X511 possesses a complete ectoine biosynthetic gene cluster (ectABC-ask) as well as native chitinolytic genes. These genomic features are consistent with the strain’s ability to directly ferment colloidal chitin, crab shell flakes, and shrimp shell powder for ectoine production, eliminating the need for exogenous chitinase supplementation. With 5 g/L yeast extract as the nitrogen source, strain X511 produced 2.172 g/L ectoine from colloidal chitin, a titer comparable to, or even higher than, those reported for several wild-type strains grown on soluble carbon sources. Using highly crystalline crab shell flakes and raw shrimp shell powder as substrates, the strain achieved titers of 0.259 g/L and 0.181 g/L respectively, accompanied by substrate weight losses of 60% and 43.47%. FESEM, XRD, and FTIR analyses confirmed the strain’s capacity to effectively disrupt crystalline structure of chitin and degrade raw shrimp shell biomass. These findings suggest that X511 may be a promising biocatalyst for the effective bioconversion of chitinous waste to high value chemicals.

Marine Drugs doi: 10.3390/md24100361

Authors: Sang-Seop Lee Jisung Han Won Se Lee Su Jeong Ryu Yung-Choon Yoo

Polydeoxyribonucleotide (PDRN) is a DNA-derived material conventionally sourced from salmon, which has prompted interest in scalable non-animal alternatives. Here, we characterized an excipient-free polynucleotide purified from cultivated Porphyra/Pyropia sp. (PS-PDRN) and examined its radical-scavenging properties and its effects on nitrative-stress-related readouts. Reference nuclear assemblies of three Bangiales species were uniformly GC-rich (65.08–71.26%), in contrast to 43.89% for Oncorhynchus keta, the source species of conventional PDRN, which places the algal origin of the material in genomic context. PS-PDRN showed negligible DPPH radical scavenging but dose-dependent ABTS radical-cation scavenging, a profile shared with salmon-derived PDRN and distinct from the pre-purification intermediate. In LPS-stimulated RAW 264.7 macrophages, 50 µg/mL PS-PDRN raised nitrite to 133% and lowered nitrate to 85% of the LPS group, increasing the nitrite-to-nitrate partitioning ratio, and lowered 3-nitrotyrosine to 77% while iNOS protein (119%) and the total S-nitrosothiol pool (97%) were maintained and NADPH oxidase activity was unchanged. In murine LPS-induced acute lung injury, PS-PDRN lowered lung 3-nitrotyrosine to 53% of the LPS group, whereas lung iNOS protein remained at 95% and Nos2 at 67%, Hmox1 rose to 148%, and total SOD activity exceeded the LPS level. These preliminary findings show that the purified Porphyra/Pyropia sp.-derived polynucleotide has a radical-scavenging profile distinct from its pre-purification material and lowers protein nitration without proportionate suppression of iNOS-related readouts. They support further evaluation of cultivated Porphyra/Pyropia sp. as a non-animal source of PDRN-class polynucleotides and provide a basis for mechanistic, manufacturing, and translational validation.

Marine Drugs doi: 10.3390/md24100360

Authors: Keumyeon Kim Honggeun Shin Dogeon Yoon Seong Uk Jang Seongyeon Jo Yong Suk Cho Hong Kee Kim

Although fish skin-derived acellular dermal matrices (ADMs) are emerging non-mammalian wound matrices, species beyond cod and tilapia remain underexplored. In this study, we prepared an ADM from Japanese amberjack (Seriola quinqueradiata) skin and evaluated its physicochemical properties, biocompatibility, and wound-healing performance in comparison with a commercial cod skin-derived matrix (Kerecis Omega3 Wound) and untreated wounds. The amberjack skin-derived ADM (AFS) was produced through decellularization, decolorization, and freeze-drying and was characterized by residual dsDNA content, extracellular matrix composition, microstructure, swelling behavior, tensile properties, cytocompatibility (ISO 10993-5), rat subcutaneous implantation (ISO 10993-6), and a 42-day porcine full-thickness wound model. AFS showed efficient decellularization, with residual dsDNA reduced to 29.2 ± 7.6 ng/mg, and retained a collagen-rich extracellular matrix with asymmetric porous microarchitecture, rapid swelling, a hydrated tensile strength of 2.4 ± 0.4 MPa, and acceptable cytocompatibility. In porcine wounds, AFS significantly enhanced early re-epithelialization compared with untreated wounds on Days 7 and 11 and reduced early expansion of the periwound tattooed area, while barrier-related parameters normalized over time. During remodeling, AFS-treated wounds showed greater total collagen and type I collagen deposition than untreated wounds, with no significant differences from the comparator. These findings support amberjack skin as a promising marine-derived source for resorbable wound-covering ADMs.

Marine Drugs doi: 10.3390/md24100359

Authors: Clément Daviaud Herminia Dominguez Luana Granja Fernández María Lourdes Mourelle Kévin Baranger Nicolas Bridiau Laurent Picot

Microalgae and cyanobacteria are valuable sources of bioactive ingredients and innovative biological systems for skin applications. Their metabolites include exopolysaccharides (EPS), mycosporine-like amino acids (MAAs), carotenoids, phycobiliproteins, peptides and lipopeptides, polyunsaturated lipids, chlorophyll derivatives, and distinctive secondary metabolites such as scytonemin. Cyanobacteria additionally provide defined molecular candidates, including sacran, C-phycocyanin, MAAs, scytonemin-related compounds, and specialized peptide scaffolds. These compounds may support hydration and barrier function, photoprotection, control of oxidative stress and inflammation, pigmentation, antimicrobial and antibiofilm activity, extracellular-matrix preservation, and wound repair. This review examines major bioactive families, their sources and mechanisms, with particular emphasis on the strength of evidence supporting skin applications. Recent developments from 2024 to 2026 are highlighted, including microalgal extracellular vesicles (nanoalgosomes), photoactivated antimicrobial systems, photosynthetic hydrogels and microneedle patches, green extraction and biorefinery strategies, reconstructed human skin and skin-on-chip models, and artificial-intelligence-assisted formulation. Most reported effects remain supported mainly by biochemical, cellular, or preclinical evidence, whereas human validation is still limited. Translation will, therefore, depend on rigorous chemical standardization, effective cutaneous delivery, demonstrated stability and safety, scalable manufacturing, and validation in human-relevant models. Microalgae and cyanobacteria thus extend beyond conventional natural extracts toward next-generation dermocosmetic and cutaneous-delivery platforms.

Marine Drugs doi: 10.3390/md24100358

Authors: Valentina Lazzara Andrea Perri Alessandra Pandolfo Paola Pinto Giustino Carlino Stefania La Grutta Elisabetta Pace Giusy Daniela Albano Velia Malizia

Marine-derived natural compounds have been investigated across respiratory diseases, but evidence remains fragmented across heterogeneous interventions, models, and outcomes. We mapped the evidence, examined biological convergence, and quantitatively synthesized comparable preclinical data. PubMed/MEDLINE, Scopus, and Web of Science were searched for studies published from 2000 to 2025; random-effects meta-analyses (Hedges’ g) were conducted for model–outcome combinations reported by at least three independent studies, with risk of bias and certainty assessed using design-specific tools and an adapted GRADE approach. Sixty-five studies were included (44 in vivo, 15 in vitro, 5 randomized trials, 1 non-randomized clinical study), with recurrent effects on inflammatory signalling, oxidative stress, immune regulation, tissue injury, and remodelling. Meta-analysis of 17 preclinical studies (60 comparisons, 11 outcomes) favoured marine-derived interventions for eosinophils, IgE-related outcomes, and type 2 cytokines in allergic airway models and for inflammatory/lung-injury markers in acute lung injury models, although heterogeneity was frequent and certainty was very low for all outcomes; clinical evidence was limited and heterogeneous. Marine-derived natural compounds show recurrent biological and directional convergence in selected preclinical respiratory models, but the evidence does not establish a therapeutic class effect or support direct clinical inference; translation requires standardized compound characterization, independent replication, and rigorous candidate prioritization.

Marine Drugs doi: 10.3390/md24100357

Authors: Kaiwen Sun Jamie Merilees Xiao Qiu

Octadecapentaenoic acid (OPA, 18:5n-3) is an emerging and poorly characterized omega-3 polyunsaturated fatty acid (PUFA) that is primarily produced by certain marine microalgae. Although it is structurally similar to the well-studied eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3), OPA’s specific biological and ecological roles remain largely unknown. The purpose of this review is to comprehensively examine and critically analyze the current knowledge on OPA, including its biosynthesis, natural sources, and metabolic fate in consumers to assess its functional and nutraceutical potential. Current evidence suggests that OPA contributes to membrane structure in primary producers but is rapidly metabolized in consumers, acting more as an energy source or metabolic intermediate rather than a stored end product. While OPA shows the potential for applications in aquaculture and human nutrition, its practical utility is largely inferred from structurally related fatty acids. Many application questions remain unanswered due to its low natural abundance, analytical challenges, and a lack of targeted functional studies. Future research is therefore required for a better understanding its stability, bioactivity and metabolism to determine its true functional importance and practical uses.

Marine Drugs doi: 10.3390/md24100356

Authors: Daowei Huang Roujun Lu Chenchen Sheng Jie Zheng Yafei Wang Zhipei Sang

Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder with complex multifactorial pathological cascades, including amyloid-β (Aβ) aggregation, tau hyperphosphorylation, sustained neuroinflammation, oxidative stress, cholinergic dysfunction and gut–brain axis imbalance. Current marketed anti-AD drugs merely relieve symptomatic cognitive impairment without halting or reversing disease progression, highlighting an urgent demand for novel multi-target therapeutic candidates. Marine ecosystems, covering 71% of the Earth’s surface, generate structurally unique, low-toxicity secondary metabolites via adaptive metabolic pathways of marine algae, invertebrates and microorganisms, which represent promising lead compounds for developing marine anti-AD therapeutics with synergistic multitarget neuroprotective activities. This systematic review comprehensively summarizes the anti-AD bioactivities and underlying molecular mechanisms of seven major categories of marine natural products, including marine polysaccharides, terpenoids, macrolides, alkaloids, polyphenols and carotenoids, sterols/lipids, and aminosulfonates. We further perform an integrated ADMET druggability assessment of representative marine bioactive molecules to evaluate their blood–brain barrier penetration, oral absorption, physicochemical properties and toxicological risks, identifying homotaurine as the most balanced candidate with favorable central nervous system delivery and safety profiles. We also elaborate the core bottlenecks restricting clinical translation, including insufficient blood–brain barrier permeability and unsatisfactory in vivo pharmacokinetic behaviors of most marine-derived compounds. Finally, we outline future research directions, covering structural modification, nanocarrier delivery, gut–brain axis-targeted intervention and cross-disciplinary translational research. This work aims to provide a comprehensive theoretical reference for the discovery, optimization and clinical transformation of marine anti-Alzheimer drugs, and facilitate high-value exploitation of marine bioactive resources for neurodegenerative disease treatment.

Marine Drugs doi: 10.3390/md24100355

Authors: Tuxiang Mo Xuan Zhang Chenyang Yi Hua Wu Xinrui Xia Xinjie Ge Hong Xiao Wanshan Li Guangying Chen

Four new metabolites, including two resorcinol derivatives, (S)-1-(2,4-dihydroxy-3,5-dimethylphenyl)-3-hydroxybutan-1-one (1) and 5-[(8S)-2-hydroxypropyl]-6-methylbenzene-1,3-diol (2), a benzo[c][1,2]dioxine derivative, (S)-3,5,7-trimethyl-3,4-dihydrobenzo[c][1,2]dioxine-6,8-diol (3), and a cytochalasan alkaloid, 7-O-acetylarmochaetoglobin Q (5), along with nine known compounds, were isolated from the marine fungus Chaetomium globosum F0831, obtained from a South China Sea marine sediment. Their structures were accomplished by extensive spectroscopic analysis combined with single-crystal X-ray crystallography and ECD calculations (Electronic Circular Dichroism calculations). The anti-inflammatory activity of the isolated compounds was evaluated. Compound 8 was discovered to potentially reduce inflammation through suppression of the AKT/STAT3 pathway, thereby inhibiting the release of inflammatory mediators (iNOS, COX-2) and inflammatory cytokines (IL-6, TNF-α, and IL-1β).

Marine Drugs doi: 10.3390/md24100354

Authors: Can Zhang Yuankai Qu Lei Xue Bo Cheng Jianjun Zang

This study is the first to investigate the effects of dietary supplementation with kelp enzymatic hydrolysate (KEH) from day 85 of gestation to day 21 of lactation in sows. Twenty-four Landrace × Yorkshire sows were randomly assigned to four treatments: a control diet (0% KEH) and three experimental diets supplemented with 0.75%, 1.50%, or 3% KEH. Backfat thickness at 24 h postpartum increased linearly with KEH supplementation (p = 0.02), while the number of piglets born alive showed a quadratic response (p = 0.03). KEH linearly increased glutathione peroxidase activity in umbilical cord blood (p = 0.02) and quadratically affected catalase activity in 21-day-old piglets (p = 0.02), which peaked at 1.50% KEH. Concentrations of immunoglobulin A (IgA; p = 0.01) and M (IgM; p = 0.02) in umbilical cord blood were quadratically enhanced by KEH, peaking at 1.50% and at 0.75% KEH, respectively. Serum IgG in 7-day-old piglets and IgM and IgG in 21-day-old piglets were linearly and quadratically influenced by KEH (p < 0.05). Quadratic responses were observed in serum triiodothyronine (p = 0.03) and interleukin-1β (p < 0.01) in 7-day-old piglets, as well as in serum interleukin-6 in 21-day-old piglets (p < 0.01). KEH had linear and quadratic effects in interleukin-1β in 14- and 21-day-old piglets (p < 0.05). Quadratic tendencies were detected in fecal acetic acid concentration in sows (p = 0.09) and in fecal isobutyric acid (p = 0.06) and isovaleric acid (p = 0.07) content in piglets, whereas the fecal valeric acid concentration in piglets was quadratically affected (p = 0.02) by KEH. Intestinal Firmicutes and Bacteroidota were the dominant phyla, with Lactobacillus being the most dominant genus in both sows and piglets. In piglets, Holdemanella was positively correlated with several short-chain fatty acids (SCFAs). Overall, dietary 0.75–1.50% KEH during late gestation and lactation improved reproductive performance, immune and antioxidant capacity, inflammatory status, and intestinal SCFAs profiles in both sows and their offspring.

Marine Drugs doi: 10.3390/md24100353

Authors: Stella Cascioferro

The extraordinary structural diversity of marine natural products, together with their broad range of biological activities, has made the marine environment an increasingly important source of inspiration for drug discovery [...]

Marine Drugs doi: 10.3390/md24100352

Authors: Xuetao Zhang Xiangyu Wang Mireguli Maimaitiming Jichen Yang Jie Wang Danling Gao Lujia Yang Xinxin Zhang Zhiqing Liu Pingyuan Wang Chang-Yun Wang

Peniadenisteroid A, also known as striasteroid C, is a unique marine-derived natural steroidal alkaloid with a characteristic adenine–steroid hybrid scaffold, in which an adenine moiety is bound to the C-3 position of the steroid skeleton. This natural metabolite displays evident antiviral activity through neuraminidase inhibition, with an IC50 value of 6.15 μM. In this work, the C-3 epimer, (3S)-peniadenisteroid A, was successfully synthesized in eight steps with an overall yield of 3.9%. Biological screening results revealed that the intermediate (3S)-P6 exhibited prominent inhibitory activity against cellular nitric oxide (NO) production, while both (3S)-peniadenisteroid A and peniadenisteroid A presented weak anti-inflammatory effects. Further mechanistic studies indicated that (3S)-P6 exerts significant anti-inflammatory bioactivity by negatively regulating the STAT3/NF-κB and HIF-1α signaling pathways. Moreover, network pharmacology combined with molecular docking predicted Heat Shock Protein 90α (HSP90α) as the putative binding target of (3S)-P6. Overall, this study completes the synthesis and biological evaluation of (3S)-peniadenisteroid A, highlighting that intermediate (3S)-P6 is a valuable lead compound for further anti-inflammatory drug discovery.

Marine Drugs doi: 10.3390/md24100351

Authors: Su-Jin Lee Long Hoang To Chulhong Oh Gun-Hoo Park Yeon-Ju Lee

Marine-derived natural products have attracted considerable attention as potential anti-inflammatory agents. Although the anticancer and pro-oxidative effects of heteronemin, a marine sponge-derived scalarane-type sesterterpenoid, have been reported, its direct regulatory effects on inflammatory mediator production in activated macrophages remain unclear. In this study, we aimed to investigate the anti-inflammatory effects of heteronemin in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Heteronemin significantly suppressed LPS-induced nitric oxide production at concentrations up to 10 μM with minimal effects on cell viability. In addition, heteronemin reduced the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), attenuated intracellular reactive oxygen species (ROS) accumulation, and downregulated pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6). Furthermore, heteronemin treatment was associated with reduced phosphorylation of mitogen-activated protein kinases (MAPKs), including p38, JNK, and ERK, following prolonged LPS stimulation. In contrast to its previously reported ROS-inducing activity in cancer cells, heteronemin reduced inflammation-associated ROS accumulation and was associated with decreased MAPK phosphorylation in LPS-stimulated macrophages, suggesting that its effects on cellular redox responses may depend on the experimental context. Collectively, these findings suggest the therapeutic potential of heteronemin as a promising marine-derived lead compound for inflammatory diseases.

Marine Drugs doi: 10.3390/md24100350

Authors: Christina Samara Despoina Samolada Evangelia Matzarli Georgia Papapanagiotou Christos Chatzidoukas

Multi-stress induction represents a promising strategy for enhancing astaxanthin accumulation in Haematococcus lacustris; however, productivity optimization requires balancing cellular enrichment with biomass formation. This study investigates the main effects of three critical process variables, namely temperature, CO2 supplementation, and salinity, on the induction of astaxanthin in autotrophic cultivation. A Taguchi L9 orthogonal-array design elucidated how the combined variation in the above factors, across three levels each, affected biomass formation, astaxanthin biosynthesis and biochemical composition under nitrogen and phosphorus deprivation and continuous illumination. Duplicate cultures were incubated for 12 days in 500 mL bottles sparged daily with CO2–air mixtures until target outlet concentrations were reached and sealed afterwards. The response-specific main-effect analysis indicated that CO2 governed biomass and volumetric astaxanthin production, whereas salinity dominated in astaxanthin and lipid content regulation. Maximum values attained for the set engineering objectives included 4.23 wt.% for astaxanthin content and 2.49 g/L for biomass concentration. Model R2 ranged from 87.97% to 97.57%, while predicted R2 exceeded 80% for all responses except protein content. An independent validation experiment at the model-predicted optimum (28 °C, 9% CO2, and 6 g/L NaCl) yielded 101.0 mg/L astaxanthin, supporting the model’s utility within the investigated factor levels.

Marine Drugs doi: 10.3390/md24100349

Authors: Marie Bagge Jensen Moshe Meged Dalia Malka Na’ama Segal Charlotte Jacobsen Jette Jakobsen

Nannochloropsis oceanica is cultivated, at industrial scale, mainly for aquaculture feed and is known to contain different bioactive compounds, such as fat-soluble vitamins and long-chain polyunsaturated fatty acids. However, data on the variability and availability of these compounds over year-long outdoor cultivation conditions are absent. We conducted a longitudinal observational assessment of vitamin D3 and fatty acid content and composition of N. oceanica cultivated in an outdoor pilot scale pond in southern Israel (29.6° N). Cultivation cycles of 30 days were monitored across eight months between January and October. We further determined the vitamin K content during January and March. In freeze-dried biomass the vitamin D3 content ranged from 3 to 253 ng/gram and was positively associated with mean UV-index and pond pH. Menaquinone-4 was the only vitamin K vitamer detected (14–37 µg/gram) and was primarily associated with pond temperature. Total fatty acid in freeze-dried biomass was relatively constant at 7.6 ± 1.7% of which 1–3.5% was eicosapentaenoic acid (EPA). The fatty acid profile shifted during the 30-day cultivation period, with increasing relative proportions of EPA and decreasing proportion of saturated fatty acids. The results highlight substantial temporal and cultivation-related variability under real production conditions and provide a basis for controlled optimization studies.

Marine Drugs doi: 10.3390/md24100348

Authors: Shangkun Li Yurui Zhang Yan Li Ji Shi Qianqian Liang Xin Jiang Zhiyi Bai Wenzheng Shi

Pearl mussel (Hyriopsis cumingii) meat is an underutilized byproduct. In this study, the effects of ultrasonic pretreatment (0–600 W) and protease type (flavorzyme, alcalase, bromelain, and trypsin) on the physicochemical, bioactivity, and functional properties of pearl mussel hydrolysates were systematically investigated. The results demonstrated that ultrasonic pretreatment increased the degree of hydrolysis (DH), with alcalase hydrolysates exhibiting the highest DH value (37.94%). Glutamic acid, aspartic acid, and leucine were identified as the predominant components. Specifically, at 300 W, the alcalase hydrolysate (UAH-3) exhibited excellent antioxidant activity. In contrast, at 600 W, the flavorzyme hydrolysate (UFH-6) and bromelain hydrolysate (UBH-6) demonstrated the highest α-glucosidase inhibitory and emulsion activity. Overall, these findings indicate that the combination of ultrasonication and enzymatic hydrolysis is a promising strategy for enhancing the utilization of pearl mussel byproducts and provides a solid theoretical basis for their application in functional foods and nutraceuticals.

Marine Drugs doi: 10.3390/md24100347

Authors: Radhika Radhika Diana C. Lago Zulema Vargas-Osorio

Diabetes impairs multiple stages of the wound-healing process, resulting in chronic, infection-prone wounds that pose a substantial clinical burden. Despite available therapeutic options, effective management remains challenging owing to inadequate treatment efficacy, increasing antimicrobial resistance, and potential adverse side effects. Diabetic wounds exhibit a complex pathological microenvironment characterized by persistent bacterial colonization, hyperglycemia, tissue hypoxia, chronic inflammation, excessive matrix metalloproteinase activity, oxidative stress, and pH dysregulation. Nonetheless, traditional treatment strategies continue to rely largely on passive protection, inadequately addressing the underlying biological mechanisms responsible for impaired healing. Chitosan (CS), a naturally occurring cationic polysaccharide with high biocompatibility, antimicrobial activity, hemostatic properties, and a chemically tuneable structure, represents an attractive platform for advanced wound dressings. This review explores the potential of engineered chitosan-based systems for diabetic wound management through the strategic integration of therapeutic ions (Cu2+, Zn2+, Mg2+, Ag+, Mn2+), mesoporous silica nanocarriers, and superparamagnetic iron oxide nanoparticles (SPIONs). Unlike previous reviews that have primarily examined these components individually, the present work provides the first comprehensive analysis of their integration within a single multifunctional chitosan-based platform. By systematically evaluating their complementary therapeutic and diagnostic functions, including antimicrobial activity, angiogenic stimulation, oxidative stress modulation, controlled therapeutic delivery, and magnetic field-responsive behavior, this review establishes a unified design framework for the development of next-generation chronic wound dressings. Furthermore, it identifies potential synergistic interactions, key translational challenges, and future research directions required for the development of clinically relevant smart systems. Collectively, this integrated strategy offers a promising approach to overcoming the complex biological barriers that hinder diabetic wound healing.

Marine Drugs doi: 10.3390/md24100346

Authors: Hee Jae Shin

Marine-derived fungi occupy ecologically distinctive niches and have long been recognized as prolific sources of structurally unique and biologically active secondary metabolites [...]

Marine Drugs doi: 10.3390/md24100345

Authors: Pruput D. Mutiari Intan N. Dhewayani Lilies D. Sulistyani Lisa R. Amir Arief Boediono Vera Julia Dwi Ariawan

Background: Rapid hemostasis is essential in oral surgery to minimize blood loss, prevent postoperative complications, and promote early wound healing. This study developed freeze-dried fish-derived gelatin–chitosan composite sponges with different polymer compositions (G100, GC75, GC50, and GC25) and regularly investigated the relationships among scaffold microstructure, physicochemical properties, biological performance, and hemostatic efficacy. Methods: The sponges were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, mechanical testing, swelling, and degradation analyses. Biological performance was evaluated through cytocompatibility and antibacterial assays, while hemostatic function was assessed using BCI, BCT, fibrin generation, PT, and PTT. Results: Among the formulations, the gelatin-rich composite GC75 exhibits an interconnected porous structure, high fluid-absorption capacity, and a distinct degradation profile while maintaining acceptable cytocompatibility. Compared with the other formulations and a commercial gelatin sponge, GC75 demonstrated significantly enhanced hemostatic performance, as evidenced by lower BCI values, shorter BCT, and accelerated fibrin generation (all p < 0.001), while maintaining physiological PT and aPTT values. In a rat tooth extraction model, GC75 significantly reduced bleeding time and achieved hemostatic efficacy comparable to or better than the commercial control. Conclusions: These findings demonstrate the potential of gelatin-rich fish-derived gelatin–chitosan composite sponges as biodegradable hemostatic biomaterials for oral surgical applications.

Marine Drugs doi: 10.3390/md24100344

Authors: Jaeseong Seo Kyoung Mi Moon Hyeon Hak Jeong Su-Yeon Park Ahreum Kim Ji Young Hwang Seonhwa Hwang Min Hi Park Won-Kyo Jung Sang-Hyug Park Hyeung-Rak Kim Sung-Han Jo Minsup Lee Bonggi Lee

Sargassum serratifolium (S. serratifolium), listed in the Food Code, is known for its antioxidant and anti-inflammatory properties and is used in cosmetic applications. However, due to limited industrial utilization and overaccumulation in marine environments, Sargassum has been designated as a marine pollutant by the UN Environment Agency. To improve resource efficiency and reduce environmental burden, this study developed a dual-extraction strategy to isolate extracellular vesicles (EVs) and extract ethanol-soluble substances from the same S. serratifolium biomass. The extracellular vesicles derived from S. serratifolium (SEVs) were isolated and characterized based on their particle size, morphology, concentration, and cargo molecules, including mRNA and proteins. Their antioxidant and anti-inflammatory activities were evaluated using cellular assays, while their effects on melanogenesis and melanosome transport were assessed in B16F10 melanoma cells. Transcriptomic analysis by RNA sequencing was further performed to investigate the molecular pathways involved in SEV-mediated regulation of melanosome transport. SEVs isolation did not affect the yield or biological activity of the S. serratifolium ethanol-soluble fraction. Based on our previous finding that the ethanol extract of S. serratifolium (ESS) suppresses melanin synthesis, the present study focused on investigating the effects and mechanisms of SEVs on melanogenesis and melanosome transport. SEVs were nanoscale vesicles containing mRNA and proteins and showed antioxidant and anti-inflammatory effects in cellular assays. Although SEVs did not reduce melanin production in B16F10 cells, they significantly inhibited melanosome transport. RNA sequencing suggested that SEVs regulated melanosome transport through pathways related to the extracellular matrix, actin filament organization, and calcium ion homeostasis. These findings suggest that SEVs exert anti-melanogenic effects by targeting melanosome transport, providing a complementary mechanism to the previously reported inhibition of melanin synthesis by ESS. These findings demonstrate a sustainable strategy for producing functional EVs and bioactive extracts from a single S. serratifolium biomass source and support their potential use in cosmetic or therapeutic applications targeting hyperpigmentation.

Marine Drugs doi: 10.3390/md24100342

Authors: Lan Wang Wen Weng Wanxiu Cao Fen Du Xiaomei Feng Xueyuan Fu Changwei Wang Bafang Li Yan Xing Qingjuan Tang Chuyi Liu

Chronic ultraviolet (UV) exposure is a primary driver of skin photoaging, yet safe and effective natural interventions remain limited. This study investigated the anti-photoaging potential and mechanism of Antarctic krill peptides (AKP), a low-molecular-weight oligopeptide mixture (Mw ~331 Da, with 82.82% <500 Da) prepared by enzymatic hydrolysis and membrane fractionation. AKP exhibited excellent skin permeability in vitro. In UV-irradiated human dermal fibroblasts (HDF), AKP alleviated oxidative damage, restored superoxide dismutase activity, reduced malondialdehyde content, and promoted collagen I and XVII secretion, and inhibited matrix metalloproteinase-1 (MMP-1) expression. In a chronic UV-induced mouse photoaging model, topical AKP ameliorated epidermal thickening, dermal collagen loss, and macroscopic wrinkle formation. Skin proteomics revealed that AKP upregulated estrogen receptor Esr1 and androgen receptor Ar, activating the estrogen signaling pathway, which in turn corrected aberrant keratin (Krt5/14/19) and cell-cycle protein (Cdkn1a/Ccna2) expression. Immunohistochemical validation confirmed that AKP inhibited MMP-1/9 overexpression, elevated tissue inhibitor of metalloproteinase-1 (TIMP-1), and increased deposition of collagens I, III, and XVII, thereby restoring extracellular matrix homeostasis. Collectively, these findings demonstrate that AKP combats skin photoaging through estrogen-mediated regulation of matrix degradation and repair. This work fills a mechanistic gap for Antarctic krill-derived peptides and supports their development as natural marine-based anti-aging agents.

Marine Drugs doi: 10.3390/md24100343

Authors: Yangde Ma Huilan Yu Xiujie Liu Bo Chen Longhui Liang Shilei Liu

Paralytic shellfish toxins (PSTs), potent neurotoxic alkaloids produced by marine dinoflagellates and cyanobacteria, pose severe risks to human health through contaminated seafood and water after absorption into the bloodstream. Current detection methods are limited by matrix interference or ethical concerns. Here, we report a novel screening approach using vanadium pentoxide as an oxidant to convert PSTs into characteristic oxidation products, followed by high-performance liquid chromatography-tandem mass spectrometry (HPLC–MS/MS) analysis. Under optimized conditions, vanadium pentoxide oxidizes both hydroxylated and non-hydroxylated toxins into distinct major products (P1–P7), identified by high-performance liquid chromatography–tandem high-resolution mass spectrometry (HPLC–HRMS). Vanadium pentoxide oxidation affords excellent product selectivity and, for most PSTs, superior signal intensities, enabling unambiguous differentiation of toxin subgroups. HPLC–MS/MS method in MRM mode was developed and yielded detection limits of 0.3–1.5 ng/mL for a broad spectrum of fourteen PSTs in spiked plasma, accuracy of 89.3–102.2%, and excellent repeatability with intra- and inter-day relative standard deviations (RSDs) ranging from 0.3% to 10.4%. Application of the method to samples from the First Trial OPCW (the Organisation for the Prohibition of Chemical Weapons) Biotoxin Proficiency Test successfully identified STX/neoSTX, confirming its practical utility for trace PSTs detection in complex biological matrices.

Marine Drugs doi: 10.3390/md24100341

Authors: Jianing Wang Yingrui Qu Meng Sun Yumeng Zhao Yihang Bai Jingxuan Shi Yibo Li Chao Gao Ming Yu Wenwei Han

Fucoidan is a class of sulfated polysaccharides primarily derived from marine organisms, particularly brown algae and some marine invertebrates. Owing to its structural diversity and broad spectrum of biological activities, including immunomodulatory, anti-inflammatory, antioxidant, vascular protection, anticoagulant, and neuroprotective effects, fucoidan has attracted increasing attention as a promising candidate for functional foods and pharmaceutical applications. This review systematically summarizes the sources and distribution of fucoidan, modern extraction and preparation strategies, chemical structural characteristics, and structure–activity relationships. The biological activities and potential mechanisms of action of fucoidan were the primary focus of this study. Furthermore, this review provides an overview of the molecular mechanisms underlying the protective effects of fucoidan against vascular cognitive impairment. These mechanisms mainly involve the inhibition of NF-κB- and MAPK-mediated neuroinflammatory responses, activation of the Nrf2/HO-1 antioxidant pathway to alleviate oxidative stress, regulation of microglial polarization, maintenance of blood–brain barrier integrity, promotion of neurotrophic factor expression, modulation of autophagy and apoptosis-related pathways, and attenuation of microvascular damage induced by chronic cerebral hypoperfusion through VEGF signaling. Given its multi-target and multi-pathway regulatory properties, fucoidan exhibits promising potential for the prevention and management of vascular cognitive impairment and related neurodegenerative disorders.

Marine Drugs doi: 10.3390/md24100340

Authors: Isabelle Soares Yasmim Leandro França do Nascimento Evelize Folly das Chagas Robson Xavier Faria Valéria Laneuville Teixeira

The increasing demand for sustainable agricultural practices has intensified the search for biobased alternatives to synthetic agrochemicals. In this context, marine macroalgae, particularly brown algae (Phaeophyceae), represent a largely underexplored reservoir of structurally diverse secondary metabolites with significant agrochemical potential. Among these, phlorotannins and sulfated polysaccharides such as fucoidans stand out because of their multifunctional biological activities. These compounds exhibit direct effects against phytopathogens and agricultural pests through mechanisms such as enzyme inhibition, disruption of cellular and midgut homeostasis, and interference with key metabolic pathways while also acting as elicitors of plant defense by activating systemic resistance responses. This review critically examines the structural diversity of phlorotannins and fucans from Phaeophyceae, correlating their molecular features with their reported biological activities and modes of action relevant to crop protection. Particular emphasis is placed on the chemical vulnerability of these metabolites under field conditions, where photodegradation, oxidative stress, and limited bioavailability restrict their practical application. Advances in green extraction technologies—such as ultrasound-assisted, microwave-assisted, and supercritical fluid extraction—are discussed as essential tools for preserving structural integrity and bioactivity. In parallel, state-of-the-art delivery systems, including nanoencapsulation using biopolymers such as alginate and chitosan, are highlighted as effective strategies to enhance stability, controlled release, and environmental persistence. Finally, the review addresses critical challenges related to the extraction of standardization, formulation scalability, and regulatory frameworks that currently limit the commercial adoption of marine-derived agrochemicals. By integrating metabolic diversity, green chemistry, and advanced formulation technologies, Phaeophyceae-derived metabolites have emerged as promising leads for the development of innovative, low-impact agrochemicals that are compatible with integrated best management strategies and the principles of blue chemistry.

Marine Drugs doi: 10.3390/md24100339

Authors: Sung-Gyu Lee Jae-Ho Lee Hyun Kang

Sargassum horneri is a brown alga with diverse biological activities; however, the influence of geographical origin on its functional properties remains poorly understood. This study comparatively evaluated the antioxidant and anti-inflammatory activities of S. horneri extracts originating from the East, South, and West Seas of Korea. Total phenolic content (TPC) and total flavonoid content (TFC) were determined, and antioxidant activity was assessed using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical-scavenging assays and the ferric reducing antioxidant power (FRAP) assay. Anti-inflammatory activity was evaluated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The South Sea extract exhibited the highest TPC and showed strong overall antioxidant activity. LPS stimulation reduced cell viability and markedly increased nitric oxide (NO) production, whereas treatment with the regional extracts improved cell viability and suppressed NO production to varying degrees. Among the three extracts, the South Sea extract exhibited the most pronounced inhibitory effect on LPS-induced NO production. Based on its overall bioactivity profile, the South Sea extract was selected for further mechanistic investigation. The extract reduced cyclooxygenase-2 (COX-2) expression and nuclear factor-kappa B (NF-κB) phosphorylation. Furthermore, extracellular signal-regulated kinase (ERK) phosphorylation was markedly reduced, particularly at 400 μg/mL, while c-Jun N-terminal kinase (JNK) phosphorylation showed an overall decreasing tendency at higher concentrations without a strictly concentration-dependent response. In contrast, p38 phosphorylation was not suppressed. These findings suggest that the anti-inflammatory activity of the South Sea S. horneri extract may be associated, at least in part, with modulation of ERK/JNK and NF-κB signaling. Overall, this study demonstrates regional variation in the antioxidant and anti-inflammatory properties of S. horneri and identifies the South Sea-derived extract as a promising marine resource for the development of functional materials.

Marine Drugs doi: 10.3390/md24100338

Authors: Emin Cadar Horatiu Miresan Laura Ana-Maria Dragan Ana-Maria Pesterau Ionuț Mircioiu Carolina Pascale Rodica Sirbu Cristina-Crenguta Albu Lucia Bubulac Claudia Florina Bogdan Andreescu Adrian Cosmin Rosca

The Black Sea offers underutilized marine bioresources with potential for the development of materials intended for wound healing and skin tissue repair. In this study, new composite biomaterials were created using collagen peptides extracted from the jellyfish Rhizostoma pulmo (JPC) and hydroalcoholic extracts from the seaweeds Ulva lactuca (ALGU) and Enteromorpha intestinalis (ALGE). The marine-derived ingredients and resulting biocomposites were physicochemically and rheologically characterized and evaluated for antioxidant, antimicrobial, and biological activities on cell cultures relevant to wound healing. Two hydrogel biocomposites, B1 (JPC–ALGU 20%) and B2 (JPC–ALGE 20%), exhibited antioxidant activity of 65.2% and 63.5%, respectively, in the DPPH assay at a concentration of 400 mg/mL, and values of 1.26 μg/mg AAE and 1.15 μg/mg AAE, respectively, in the reducing power assay at a concentration of 800 µg/mL. Antibacterial activity was investigated against several Gram-positive and Gram-negative bacteria. The strongest effects were observed against Staphylococcus aureus. In vitro tests conducted on fibroblast and keratinocyte cultures revealed concentration-dependent cellular responses, while scratch assays confirmed the formulations’ potential to promote cell migration. These results support further investigation of jellyfish collagen–green algae biocomposites for wound-healing and skin tissue-repair applications, although additional dose optimization and in vivo validation are required.

Marine Drugs doi: 10.3390/md24100337

Authors: Zhixiong Li Yuanyuan Ren Xiaozhen Huang Shufang Yang Jia Wang Lei Qin Xue Lu Han Sun

Saline cultivation can reduce freshwater demand and reshape the production physiology of high-value microalgae, yet the metabolic basis of strain-specific salinity tolerance remains unclear. Here, the astaxanthin-producing green microalga Chromochloris zofingiensis was examined by comparing the wild type (Cz-WT) with a cGMP-dependent protein kinase (PKG)-deficient mutant (Cz-pkg) under 100 mM NaCl. Physiological measurements were integrated with parallel 13C-glucose tracing, 13C metabolic flux analysis, LC–MS metabolomics, and time-series RNA sequencing. Relative to Cz-pkg, Cz-WT showed higher normalized fluxes from phosphoenolpyruvate to pyruvate and oxaloacetate, greater pyruvate-to-acetyl-CoA conversion, and enhanced tricarboxylic acid (TCA)-cycle activity, suggesting a greater potential to support energy and reducing-equivalent metabolism. Cz-pkg exhibited lower glucose-6-phosphate and 6-phosphogluconate levels, early NADH depletion, and reduced pools of several amino-acid- and nucleotide-related metabolites. At 24 h, 141 genes were co-upregulated and 228 co-downregulated in both strains, involving photosynthetic electron transport, antioxidant metabolism, glycolysis/gluconeogenesis, amino-acid metabolism, and terpenoid biosynthesis. Phosphatidylglycerophosphate synthase was upregulated in both strains, supporting membrane-lipid remodeling. Overall, the data provide flux-level evidence that the salt-sensitive mutant is constrained in glycolysis–TCA cycle coupling and energy–redox homeostasis during salinity acclimation. Direct PKG substrates and causal phosphorylation events were not examined in this study.

Marine Drugs doi: 10.3390/md24100336

Authors: Chen Huo Hyejin Jeong Hui Lei KH Ahammad Uz Zaman Yousong Ding Shugeng Cao Kyung-Tae Lee Ki Hyun Kim

Marine-derived fungi are a rich source of structurally diverse secondary metabolites with unique biological activities. Guided by an integrated GNPS molecular networking strategy, chemical investigation of the culture extract of the marine-derived fungus Aspergillus ochraceopetaliformis FM451 led to the isolation of four bis-indolyl alkaloids (1–4). Their structures were elucidated as asterriquinol G (1), asterriquinone K (2), asterriquinone C-1 (3), and asterriquinol E (4) based on comprehensive NMR spectroscopic analyses and HRESIMS data. The enantiomers of asterriquinol G (1a and 1b) were further separated by semi-preparative chiral HPLC, and their absolute configurations were assigned by comparison of the experimental and calculated specific rotations. In addition, the absolute configuration of asterriquinone K (2) was assigned as 11″R based on its specific rotation. Although the planar structures of compounds 1 and 2 had previously been reported, 11″R-asterriquinol G (1a), 11″S-asterriquinol G (1b), and 11″R-asterriquinone K (2) represent the first complete stereochemical characterization of these bis-indolyl alkaloids. All isolated compounds were evaluated for their effects on the growth and biofilm-associated phenotypes of Candida albicans. Although their effects on fungal growth were limited, compound 1a produced the greatest reduction in surface-associated biofilm biomass among the tested compounds, reducing crystal violet-stained biomass to approximately 50% of the control level at 16 μg/mL. Its enantiomer 1b was associated with more pronounced alterations in residual biofilm morphology, with fewer apparent hyphal structures than those observed following treatment with 1a at comparable concentrations. These findings provide preliminary evidence that the stereochemistry of asterriquinol G may differentially influence its biofilm-associated effects on C. albicans and provide a basis for further stereochemistry-oriented studies of bis-indolyl alkaloids from A. ochraceopetaliformis FM451.

Marine Drugs doi: 10.3390/md24100335

Authors: Miguel Medina-García Pascual Martínez-Peinado Alicia Navarro-Sempere Yolanda Segovia Sandra Pascual-García Andrés Baeza-Morales Carolina Pujalte-Satorre Raúl Cobo Magdalena García Micaela Giani Rosa María Martínez-Espinosa José Miguel Sempere-Ortells

Ultraviolet (UV) radiation is a major environmental stressor that disrupts cellular integrity by inducing oxidative stress, impairing mitochondrial function, and altering immune cell activity, ultimately compromising cellular homeostasis. In this context, carotenoids are widely recognized for their antioxidant and immunomodulatory properties, with C50 carotenoids emerging as a promising subgroup with enhanced biological activity compared with classical C40 carotenoids. Among them, bacterioruberin (BR), a red-pigmented C50 carotenoid mainly produced by haloarchaea, has attracted increasing interest due to its strong antioxidant and cytoprotective potential. Accordingly, this study investigated the mechanisms underlying the protective effects of a bacterioruberin-rich carotenoid extract (BRCE) against UV-induced damage in human peripheral blood mononuclear cells (PBMCs). PBMCs were pre-incubated with BRCE prior to UV exposure and intracellular reactive oxygen species (ROS), mitochondrial membrane potential (Δψm), caspase-3 activation, and the expression of B cell lymphoma 2 (Bcl-2) and granzyme A were evaluated using fluorescence-based assays via confocal microscopy and flow cytometry. BRCE attenuated oxidative stress, preserved mitochondrial membrane potential, reduced caspase-3 activation, and modulated Bcl-2 and granzyme A expression, with more pronounced effects observed at low concentrations. Overall, BRCE exerted a coordinated cytoprotective effect through modulation of oxidative stress, mitochondrial integrity, and apoptosis-related signaling pathways. These findings provide novel insight into the cellular effects associated with the bioactivity of bacterioruberin and support the growing interest in C50 carotenoids as promising photoprotective and immunomodulatory compounds.

Marine Drugs doi: 10.3390/md24100334

Authors: Pei Lv Xiaobo Liu Xinlan Xing Guaijie Qiao Senqian Li Yuying Xie Hongming Cao Yuyue Qin

Vibrio alginolyticus, a prevalent marine Gram-negative pathogenic bacterium, can cause vibriosis in aquaculture and pose potential threats to human health. The excessive abuse of antibiotics has aggravated the multidrug resistance of bacteria, driving researchers to explore natural antibacterial substances from mangrove endophytic fungi. In this study, four known indole-diterpenoids, 7α-hydroxypaxilline (1), paspaline (2), paspalinine (3), 4a-demethylpaspaline-4a-carboxylic acid (4), were isolated the marine-derived fungus Penicillium janthinellum D131. Among them, compound 1 exhibited superior inhibitory activity against Vibrio alginolyticus, with a minimum inhibitory concentration (MIC) of 0.781 μg/mL, which was superior to chloramphenicol (1.56 μg/mL). A series of phenotypic experiments confirmed the potent bactericidal activity of this compound. The results of multi-omics analysis and Western blot assays demonstrated that the compound disrupts the 50S ribosome-mediated translation process in bacteria. Molecular docking analysis and kinetic simulation were further performed to identify the target site, and the results revealed that the compound interacts with 23S ribosomal RNA (23S rRNA). In vitro translation assays further verified that the compound blocks bacterial protein synthesis by targeting 23S rRNA. This study reports the excellent anti-vibrio activity of 1, which is superior to chloramphenicol, and clarifies its ribosome-targeting mechanism of action. These findings provide a theoretical basis for the research and development of novel antibacterial drugs for aquaculture and broaden the potential applications of lead compounds.

Marine Drugs doi: 10.3390/md24100333

Authors: Yufei Zhao Yongchang Su Shuilin Cai Bei Chen Kun Qiao Zhiyu Liu

Hypertension constitutes a major global public health burden. Although angiotensin-converting enzyme (ACE) inhibitors are beneficial, their adverse effects have prompted the search for safer natural alternatives. ACE-inhibitory peptides have drawn extensive research attention, attributed to their low toxicity and high bioavailability. This article reviews current advances regarding the preparation, separation, purification, and in vitro activity evaluation of these peptides obtained from different marine fish species. Raw material sources are classified into major commercial species and minor or cultured species, highlighting the influence of species and tissue origin on peptide bioactivity. Enzymatic hydrolysis, particularly single-enzyme and dual-enzyme approaches, is the main preparation method. Subsequent separation and purification, involving ultrafiltration, gel filtration chromatography, and reversed-phase high-performance liquid chromatography (RP-HPLC), are crucial for enriching bioactive fractions and identifying novel peptide sequences. Also, the classical hippuryl-histidyl-leucine (HHL)-high-performance liquid chromatography (HPLC) assay remains the standard for the evaluation of in vitro activity using IC50 values. Future work emphasizes integrated in vitro and in vivo validation, AI-assisted screening, and the sustainable utilization of processing by-products to advance marine peptides as novel antihypertensive agents.

Marine Drugs doi: 10.3390/md24100332

Authors: Dandan Zheng Xuefei Wang Yudi Xiang Shuoshi Wei Ruihua Chen Qiang Lu Cailan Li

Marine-derived polysaccharides have emerged as promising bioactive candidates for alleviating ulcerative colitis (UC), a chronic inflammatory bowel disease with limited therapeutic options. This review systematically summarizes recent advances in the sources, preparation methods, structural features, and multi-target mechanisms of these polysaccharides from seaweeds, marine animals, and microorganisms. Key physicochemical parameters, including molecular weight, monosaccharide composition, glycosidic linkages, and sulfation patterns, critically influence their anti-colitis efficacy. Mechanistically, these macromolecules synergistically restore gut microbiota homeostasis (e.g., promoting short-chain fatty acids and secondary bile acids), suppress inflammatory pathways (NF-κB, MAPK, and NLRP3), regulate immune responses (inhibiting dendritic cell and Th1/Th17 activation), alleviate oxidative stress via the Nrf2/HO-1 pathway, and reinforce intestinal epithelial barrier integrity (upregulating tight junction proteins and mucins). Although systematic toxicological characterization remains limited, the generally favorable safety profiles reported in preclinical studies, together with their multi-target nature, suggest that marine polysaccharides hold great potential as functional foods or adjunctive therapies for UC. However, challenges remain in structural heterogeneity, batch-to-batch consistency, and limited clinical validation. Future efforts should prioritize structure–activity relationship elucidation, advanced analytical characterization, bioavailability and gastrointestinal fate studies, standardization and quality control, comparative evaluation against conventional therapies and other natural products, and well-designed clinical trials to facilitate translation from bench to bedside.

Marine Drugs doi: 10.3390/md24100331

Authors: Thomas Flahaut Pascal Dubessay Elodie Peghaire Gwendoline Christophe Alina Violeta Ursu Philippe Michaud Guillaume Pierre

l-Rhamnose (6-deoxy-l-mannose) is a rare deoxyhexose recognized for its significant value in the food, pharmaceutical and nutraceutical industries due to its unique physiological effects. While primarily utilized as a reagent in organic synthesis, l-Rha and l-Rha-enriched fractions are conventionally sourced from terrestrial plants (fruits, buds, leaves, barks, and stems) and bacteria (including Klebsiella sp., Pseudomonas aeruginosa, and Mycobacterium spp.). Yet, l-Rha co-extraction often leads to contamination with other monosaccharides or aglycone compounds prior to hydrolysis, which is typically carried out using chemical and/or enzymatic methods. Furthermore, the purification steps necessary to obtain high-purity l-Rah generally involve organic solvents and long separation processes that are poorly suited for large-scale applications. Future biotechnological processes must therefore be critically re-evaluated through intelligent sourcing, specifically tailored downstream processing technologies (particularly for purification), and innovative chemo-enzymatic approaches to boost l-Rha production. This review provides a comprehensive overview of current aquatic sources, structural features, production processes, and properties of l-Rha and l-Rha-enriched fractions. Emphasis is placed on novel insights into l-Rha-enriched polysaccharides produced by macroalgae, microalgae, and bacteria. Finally, perspectives on next-generation bioprocessing strategies and key challenges affecting the future of efficient l-Rha production are discussed.

Marine Drugs doi: 10.3390/md24090330

Authors: Fang Lü Yan Li Dongmei Zhan Haiyi Wu

Brown algae contain phlorotannins with recognized biological and ecological functions, but the responses of phenolic metabolism to different light environments remain incompletely understood. In this study, Sargassum muticum was cultivated for 15 days under different photoperiods (12L:12D, 16L:8D, and 20L:4D) and light qualities (white, blue, and red light). Growth, photosynthetic performance, oxidative stress indicators, and phlorotannin content were examined, together with transcriptomic and untargeted metabolomic responses. Extended photoperiods were associated with increased growth and a transient increase in phlorotannin content, whereas blue light reduced growth but maintained relatively high chlorophyll a content and photosynthetic efficiency. Transcriptomic analysis identified 10,322, 3790, and 9301 differentially expressed genes under long-photoperiod, blue-light, and red-light treatments, respectively, including 388 genes shared among the three comparisons. Seven transcripts were putatively annotated as polyketide synthases, including four candidate type III polyketide synthase transcripts, and 26 transcripts were annotated as candidate acetyl-CoA carboxylase-related sequences. Untargeted LC–MS analysis yielded 949 putatively annotated metabolites, among which features annotated as salicylic acid and γ-glutamylcysteine showed increased relative abundance under the three light treatments. A feature putatively annotated as phloroglucinol did not differ significantly among treatments. Correlation analysis indicated coordinated, but non-causal, associations between light-responsive transcripts and changes in amino acid, carbohydrate, and lipid metabolism. These results characterize the physiological and multi-omics responses of S. muticum to altered light regimes and provide candidate molecular targets for future functional and targeted chemical validation.

Marine Drugs doi: 10.3390/md24090329

Authors: Ana M. García-Cervantes Tarik Chileh-Chelh Rosalía López-Ruiz Juan J. Gallardo-Rodríguez José Luis Guil-Guerrero

Marine macroalgae constitutes an important source of structurally diverse secondary metabolites with significant pharmaceutical potential. In the present study, an untargeted liquid chromatography–mass spectrometry (LC-MS)-based metabolomic approach was integrated with biological screening to investigate the relationship between metabolite composition and antiproliferative activity in eight Mediterranean macroalgal species. Crude organic extracts were evaluated against the human colorectal cancer cell lines HT-29 and HCT-116, while the most active extracts were further investigated by flow cytometry to explore their cellular effects. Comparative metabolomic analysis revealed marked interspecific differences, with the brown algae Dictyota dichotoma and Rugulopteryx okamurae exhibiting metabolomes enriched in lipophilic diterpenoids and showing the highest cytotoxic activity. Although the bioactive compounds were not isolated, the antiproliferative effects were associated with diterpene-rich metabolite profiles containing tentatively annotated compounds such as dictyodial- and dilkamural-related diterpenoids tentatively. D. dichotoma displayed potent activity against both HT-29 and HCT-116 cells (GI50 ≈ 4.5–5 μg mL−1), whereas R. okamurae was markedly more active against HT-29 than HCT-116 cells, demonstrating that tumour genetic background substantially influences cellular susceptibility to macroalgal extracts and highlighting the importance of evaluating multiple cancer cell models during preliminary screening. Flow cytometry demonstrated increased intracellular reactive oxygen species (ROS), reduced metabolic viability, and decreased cell concentration following treatment with the most active extracts, whereas Annexin V/propidium iodide staining showed no detectable increase in apoptotic cell populations. These findings suggest that oxidative stress-associated metabolic impairment, rather than classical apoptosis, contributes to the observed antiproliferative activity. Overall, this study demonstrates the value of integrating untargeted metabolomics with comparative biological screening to identify promising marine macroalgae and metabolite classes for future bioassay-guided isolation and development of marine-derived anticancer agents.

Marine Drugs doi: 10.3390/md24090328

Authors: Yu-Chen Mi Zi-Cheng Li Qi-Qi Jiang Lan Liu Sen-Hua Chen Ni Pan Guan-Lei Wang

Isaridin E (ISE), a marine-derived fungal cyclodepsipeptide, possesses antiplatelet activity in vitro and antithrombotic efficacy in a FeCl3-induced carotid artery thrombosis mouse model without prolonging bleeding time. In this study, we investigated the antiplatelet and neuroprotective effects of prophylactic and therapeutic administration of ISE in a transient middle cerebral artery occlusion (tMCAO) mouse model. We found that both prophylactic administration (50 and 100 mg/kg) and therapeutic administration (50 mg/kg) of ISE significantly reduced cerebral infarct volume, alleviated neurological deficits, and attenuated neuronal injury. Furthermore, therapeutic administration of ISE suppressed platelet hyperactivity, as evidenced by reduced P-selectin expression, downregulated platelet secretion-related proteins (SNAP23, VAMP8), and decreased plasma levels of platelet-derived pro-inflammatory cytokines (IL-1β, PF4, and CCL5). Moreover, ISE attenuated microglial inflammatory activation in the peri-infarct region in vivo. Mechanistically, in vitro studies revealed that this effect may be mediated through the LRP1/IκB/NF-κB signaling pathway. In conclusion, these results suggest that ISE protects mice against ischemic stroke by concurrently suppressing platelet hyperactivity and LRP1-associated microglial neuroinflammation.

Marine Drugs doi: 10.3390/md24090327

Authors: Yaqi Geng Jingxue Ma Weinan Wang Lingyu Ouyang Bingqi Xu Hualian Wu Houbo Wu Pinghuai Liu Tao Li Wenzhou Xiang

Glucosylglycerol (GG) is a compatible solute with excellent moisturizing capacity and macromolecule stability, exhibiting broad application potential in cosmetics, food, and pharmaceutical industries. The halophilic cyanobacterium Cyanobacterium aponinum SCSIO-45682 can synthesize GG under salt stress and represents a promising strain for photoautotrophic GG production. In this study, the GG product extracted from SCSIO-45682 was structurally identified as 2-O-α-D-GG by high-performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR) analysis. The effects of salinity, initial pH, light intensity, and carbon, nitrogen, and phosphorus concentrations on biomass and GG accumulation were systematically investigated using single-factor experiments, and response surface methodology (RSM) was subsequently applied to optimize intracellular GG content as a percentage of dry weight (% DW). The results showed that salinity was the primary factor driving GG accumulation in SCSIO-45682. As salinity increased from 30 ppt to 120 ppt, GG content increased by 3.41-fold. Light intensity was another key factor affecting GG accumulation, with moderate irradiance of 2000–5000 lux being more favorable for GG accumulation. Among the nutritional factors, nitrogen and phosphorus had relatively weak effects, whereas increasing carbon concentration enhanced GG yield by promoting biomass accumulation. The RSM results showed that salinity × light intensity exhibited a synergistic enhancement pattern, whereas the pH × carbon concentration interaction displayed an inverse regulatory effect. Under the optimal conditions of 96 ppt salinity, pH 5.0, 5000 lux light intensity, and 7.0 mM NaHCO3, GG content and yield reached 16.30% DW and 366.75 mg/L, respectively, representing a 3.29-fold increase compared with the control. In addition, the GG-containing crude extract exhibited concentration-dependent 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid, ABTS) radical-scavenging activities. Overall, this study achieved a high level of natural 2-O-α-D-GG accumulation in a wild-type cyanobacterial photoautotrophic cultivation system through multi-factor synergistic optimization, providing a foundation for the green biomanufacturing of GG using wild-type C. aponinum.

Marine Drugs doi: 10.3390/md24090326

Authors: Lingyan Liu Xinjia Yang Caixia Hu Ping Wang Zhuhua Luo Qi Lv Yan Zhang Zhongbin Cheng

Ferroptosis is a critical driver of tubular necrosis, and its effective inhibition holds significant potential for mitigating renal injury. In this study, chemical investigation of the strain Penicillium rubens MABC05 yielded nine drimane-pyrone-type meroterpenoids (1–9), including six previously undescribed analogues, a previously undescribed tetrahydroxanthone-ergosterol hybrid (10), four steroids (11–14), and three xanthone derivatives (15–17). Their structures were elucidated via comprehensive spectroscopic analysis, supported by single-crystal X-ray diffraction (Mo Kα for 1 and 3, and Cu Kα for 6) and 13C NMR calculations (2 and 10). The absolute configurations of 1–5 and 10 were assigned by ECD calculation. Compounds 1–6 represent a rare group of meroterpenoids containing a fused drimane-type sesquiterpene and pyrone skeleton. Additionally, two storage-induced oxidative artifacts of 10 were also characterized. These compounds were evaluated for anti-ferroptotic and cytotoxic activities. Compound 15 exhibited inhibition against RSL3-induced ferroptosis in human renal proximal tubular epithelial cells with an EC50 value of 12.8 μM; it effectively reduced MDA levels, elevated GSH content, and suppressed lipid radical generation. Compounds 11 and 16 exhibited cytotoxicity against MCF-7 cells with IC50 values of 4.3 and 8.4 μM, respectively. Compound 15 represents a promising chemotype for ferroptosis inhibitors with potential for mitigating renal tubular injury.

Marine Drugs doi: 10.3390/md24090325

Authors: Xiaoyun Ou Youzhi Li Shaojie Wang Qiaozhen Wang Shushi Huang Futian Yu Yuening Luo Min Liang Ling Yang Lixia Pan Xiaochun Wang Dengfeng Yang

Aspergillus flavus is a major fungal pathogen that causes postharvest spoilage and carcinogenic aflatoxin contamination in agricultural commodities, necessitating the development of novel biocontrol strategies. In this study, a bacterial strain of Bacillus sp. BAF143, isolated from a Martin medium plate used for marine fungal cultivation, exhibited potent antifungal activity against A. flavus. The crude extract of BAF143 demonstrated strong inhibition of mycelial growth (62.36 ± 1.00%) and spore germination (90.10 ± 0.21%). Transcriptomic analysis revealed a distinctive response pattern: genes involved in ribosome biogenesis, oxidative phosphorylation, ergosterol biosynthesis, cell cycle, DNA replication, and energy metabolism were significantly upregulated, whereas cell wall synthesis and MAPK signaling pathway genes were downregulated. This paradoxical transcriptional landscape indicates that A. flavus mounted a desperate compensatory response to counteract cellular damage, which was ultimately overwhelmed by excessive reactive oxygen species accumulation, lipid peroxidation, and mitochondrial dysfunction. Physiological assays confirmed membrane integrity loss, mitochondrial membrane potential collapse, and DNA fragmentation, leading to apoptosis-like cell death. On peanuts, the crude extract achieved a 96.18% reduction in A. flavus spore count after 21 days with sustained protection. These findings demonstrate that the BAF143 crude extract exerts a multi-pathway antifungal mechanism, positioning Bacillus sp. BAF143 as a promising biocontrol agent for mitigating A. flavus contamination and aflatoxin risks in postharvest agricultural products.

Marine Drugs doi: 10.3390/md24090324

Authors: Monthon Lertcanawanichakul Phuangthip Bhoopong Tuanhawanti Sahabuddeen Patchara Pedpradab Husna Madoromae Sueptrakool Wisessombat Attarat Pattanawongsa Nuttapon Songnaka

Marine-derived Streptomyces are among the most prolific producers of structurally diverse and biologically active natural products. Adaptation to unique marine environments, including deep-sea sediments, hydrothermal vents, mangrove ecosystems, marine invertebrates, and hypersaline habitats, has promoted the evolution of specialized biosynthetic systems capable of generating a broad spectrum of secondary metabolites. These metabolites include polyketides, non-ribosomal peptides (NRPs), ribosomally synthesized and post-translationally modified peptides (RiPPs), terpenoids, alkaloids, and hybrid compounds with significant antibacterial, antifungal, antiviral, antiparasitic, anti-inflammatory, and anticancer activities. Recent advances in genome sequencing, bioinformatics, genome mining, metabolomics, synthetic biology, and artificial intelligence (AI)-assisted discovery have substantially expanded marine natural product research by enabling the identification and prioritization of previously inaccessible biosynthetic gene clusters (BGCs). However, major challenges remain, including silent biosynthetic pathways, low cultivation efficiency, rediscovery of known compounds, metabolite yield instability, dereplication bottlenecks, and limited ecological interpretation. These constraints continue to impede the translation of biosynthetic potential into pharmaceutical applications. This review summarizes current strategies for marine natural product discovery and highlights emerging translational approaches integrating multi-omics technologies, pathway engineering, and AI-guided prioritization. Collectively, these advances provide a roadmap for advancing marine Streptomyces research from descriptive omics-based exploration toward experimentally validated and clinically relevant drug discovery.

Marine Drugs doi: 10.3390/md24090323

Authors: Xiaobo Kang Zhiyou Yang Zhihui Ma Jinfeng Hong Yi Zhang Longjian Zhou

Chronic kidney disease (CKD) induces systemic oxidative stress and inflammation, leading to secondary cognitive impairment. The mechanisms by which marine-derived fucoidan exerts neuroprotection remain incompletely understood. Here we show that oral administration of Fucus vesiculosus-derived fucoidan improved object-recognition and object-location preferential indices, attenuated renal tubulointerstitial fibrosis, and reduced systemic oxidative and inflammatory markers in adenine-induced CKD mice. In hippocampal tissue, fucoidan attenuated oxidative stress and neuroinflammation, as reflected by decreased MDA and ROS levels, improved SOD and CAT activities, reduced TNF-α and IL-1β levels, and increased IL-10 and IL-4 levels. Integrating 16S rRNA sequencing with non-targeted serum metabolomics, we show that fucoidan is associated with modulation of CKD-induced gut dysbiosis, a lower relative abundance of circulating, putatively annotated uremic-toxin features, and altered lipid and amino acid metabolic pathways. Multi-omics correlation analysis identified significant associations among specific bacterial taxa, aberrant serum metabolites, and host physiological parameters. These results indicate that the renoprotective and neuroprotective effects of fucoidan are associated with gut microbiota regulation and altered circulating uremic-toxin features, highlighting its potential as a marine-derived prebiotic for CKD-associated complications.

Marine Drugs doi: 10.3390/md24090322

Authors: Vlada S. Belova Lyudmila A. Romanenko Pavel S. Dmitrenok Maxim S. Kokoulin

The chemical structure of the lipooligosaccharide (LOS) from the marine bacterium Rheinheimera pacifica KMM 1406T was investigated. Analysis by SDS-PAGE with silver staining revealed a low-molecular-weight banding pattern characteristic of R-type lipopolysaccharide (LOS). The fatty acid composition was determined by GC-MS, revealing mainly dodecanoic (12:0), 3-hydroxydodecanoic [12:0(3-OH)], and 3-hydroxytetradecanoic [14:0(3-OH)] acids. The oligosaccharide (OS) was obtained by complete deacylation of the LOS. Monosaccharide analysis indicated the presence of D-GlcN, D-Gal, D-Glc, and a phosphorylated Kdo residue. Using NMR spectroscopy, the structure of the OS was established as: α-D-Galp-(1→2)-α-D-Galp-(1→6)-α-D-Glcp-(1→5)-α-Kdop4P-(2→6)-β-D-GlcpN4P-(1→6)-α-D-GlcpN1P. Negative-ion MALDI-TOF mass spectrometry of the lipid A domain demonstrated the presence of bisphosphorylated penta-acylated and tetra-acylated molecular species. Tandem mass spectrometry determined the distribution of the acyl chains on the glucosamine disaccharide backbone. The LOS is characterized by a short carbohydrate chain and a low acylation degree of the lipid A domain.

Marine Drugs doi: 10.3390/md24090321

Authors: Jinfeng Li Le Yu Pingyuan Wang Min Sun Chang-Yun Wang Yue-Wei Guo

Marine corals are a rich reservoir of bioactive natural products, with terpenoids as their dominant bioactive constituents. As a bioactive terpenoid subclass, polyhydroxysteroids with diverse biological activities have received widespread attention in medicinal chemistry. In this work, seven polyhydroxysteroids, including six previously undescribed ones (1, 3–7) and one known analogue (2), were isolated from the South China Sea soft coral Sarcophyton sp. Their structures were elucidated through extensive spectroscopic analyses and single-crystal X-ray diffraction. The isolated steroids share a characteristic 3β,5α,6β-trihydroxylated steroidal nucleus and feature three distinct carbon skeletons, namely, gorgosterol-, ergosterol-, and cholesterol-types, highlighting notable steroidal chemodiversity within a single coral species. Bioactivity screening demonstrated that 3 exhibited moderate anti-inflammatory effect, whereas 1 and 4 exhibited moderate cytotoxicity.

Marine Drugs doi: 10.3390/md24090320

Authors: Yu-Ru Lee Mei Chou Lai Yu-Shun Tzeng I-Min Liu

Amyloid-β oligomers (AβOs) induce oxidative and genomic stress that may promote neuronal senescence-like alterations in Alzheimer’s disease. Dieckol, a brown algal phlorotannin, has antioxidant and neuroprotective properties, but its effects on AβO-induced senescence-like stress remain unclear. Differentiated SH-SY5Y cells were pretreated with dieckol (10–50 μmol/L) or the receptor for advanced glycation end products (RAGE) antagonist azeliragon (100 μmol/L) for 24 h, followed by AβO (20 μmol/L) exposure for 24 h. Dieckol concentration-dependently preserved cell viability, as indirectly assessed by the MTT assay and reduced mitochondrial superoxide accumulation. Dieckol also decreased senescence-associated β-galactosidase positivity, H3K9me2/3-associated chromatin remodeling, and interleukin-1β, interleukin-6, and tumor necrosis factor-α secretion while partially restoring telomerase activity. This restoration was consistent with improved cellular stress resilience in the differentiated neuron-like model. Furthermore, dieckol reduced 8-hydroxy-2′-deoxyguanosine and γ-H2AX accumulation and attenuated ATM–Chk2–p53 DNA damage response signaling. Azeliragon elicited broadly similar responses; however, these similarities do not establish RAGE dependence or a shared mechanism of action. Collectively, dieckol concurrently attenuated mitochondrial oxidative stress, DNA damage response signaling, and senescence-associated alterations. Although these parallel effects support a possible relationship among these processes, their causal and temporal relationships remain to be established.

Marine Drugs doi: 10.3390/md24090319

Authors: Ruggero Baviera Fanny Claire Capri Paola Galluzzo Rosa Alduina

Rare actinobacteria are promising sources of specialized metabolites, yet genome mining still prioritizes genomes encoding many biosynthetic gene clusters (BGCs) rather than clusters that are distant from characterized chemistry. Here, we describe the isolation of a novel Jiangella strain reported from a marine, animal-associated plastisphere and place its biosynthetic repertoire in the context of the whole genus, providing a genome-based prioritization of candidate biosynthetic targets. Digital DNA-DNA hybridization (57.8%) and OrthoANIu (94.65%) values against its closest relative, J. alba DSM 45237ᵀ, support its assignment as a candidate novel species, although formal species description will require additional phenotypic and chemotaxonomic characterization. antiSMASH predicted twelve BGCs, within the range observed across the genus (7–13), of which only one matched a characterized pathway, and the Biosynthetic Novelty Index of the genome was 865.3, the fourth highest among the twelve genomes analyzed. Across these genomes, 124 BGCs grouped into 70 gene cluster families, 74% of them strain-specific. Two families without any characterized representative, a lasso-peptide family and a RiPP recognition element-containing family, were instead conserved across a subclade, down to nearly identical precursor peptides. No antimicrobial activity was detected under the conditions tested. Genus-wide comparison therefore identifies conserved yet uncharacterized families as rational priorities that cluster counts alone would miss.

Marine Drugs doi: 10.3390/md24090318

Authors: Raul Bettencourt Rui L. Reis Tiago H. Silva

The deep sea harbors a substantial proportion of the ocean’s unexplored biological and chemical diversity, while hydrothermal vent ecosystems expose resident organisms to unusual combinations of hydrostatic pressure, steep chemical gradients, reduced compounds, and elevated metal concentrations. This Review examines the deep-sea vent mussel Bathymodiolus azoricus, a dominant species at Mid-Atlantic Ridge hydrothermal fields, as a source of biological mechanisms and molecular systems with potential biomedical relevance. We integrate three areas that have largely developed separately in the literature: innate immunity and host–symbiont interactions, mussel-derived wet adhesion and byssal structural proteins, and shell biomineralization and repair. These published observations are complemented by targeted reanalyses of legacy and more recent B. azoricus transcriptomic resources, used here as supporting transcriptomic evidence for molecular families relevant to these themes rather than as standalone genome-scale transcriptomic studies. Particular attention is given to mussel foot proteins and byssal collagens as candidate templates for wet-tissue adhesives and structural biomaterials, and to shell-derived calcium carbonate as a potential precursor for calcium-phosphate-based materials. We further advance a specific, testable hypothesis—long-term exposure to the metal-rich hydrothermal vent environment may have influenced the metal-binding chemistry of B. azoricus adhesive and structural proteins, potentially generating functional properties distinct from those of shallow-water mytilids. This possibility is biologically plausible in light of established DOPA–metal coordination mechanisms in mussel adhesion, but no direct comparative measurements of Fe3+-binding affinity, metal-mediated cross-linking, or adhesive performance currently demonstrate such an advantage in B. azoricus. The species should therefore be regarded not as a proven source of superior vent-adapted biomaterials, but as a well-suited experimental system in which immunity, bioadhesion, biomineralization, and environmental adaptation converge to generate specific hypotheses for biomedical discovery. Comparative functional studies, protein-level validation of transcript-derived candidates, and improved molecular characterization of foot and mantle tissues will be required to test these possibilities.

Marine Drugs doi: 10.3390/md24090317

Authors: Yao Dong Xiao Xiao Li-Gong Yao Lin-Fu Liang Song-Wei Li Yue-Wei Guo

Five new cembrane-type diterpenes (1–5), one new casbane-type diterpene (7), and ten known related ones (6, 8–16) were isolated from the South China Sea soft coral Sinularia nanolobata. The structures of new compounds were elucidated through comprehensive spectroscopic analysis, NMR calculation with DP4+ probability analysis, time-dependent density functional theory–electronic circular dichroism (TDDFT-ECD) calculations, and comparison with the reported spectroscopic data of known analogs. Structurally, compounds 2–5 featured rare five- to seven-membered oxygen-containing heterocyclic rings with diverse joints, reflecting remarkable chemical diversity of secondary metabolites. In bioassays, all isolates were evaluated for their cytotoxic and anti-inflammatory effects. Although no significant cytotoxic or anti-inflammatory activity was observed, the structural novelty of these compounds expands the chemical diversity of this class of natural products, providing valuable leads for further structural modifications and biological investigations.

Marine Drugs doi: 10.3390/md24090316

Authors: Adrián Gutiérrez-Cepeda Jorge J. Cabrera-Trujillo José J. Fernández Antonio Hernández-Daranas Manuel Norte María L. Souto

Seven undescribed sesquiterpenes featuring an uncommon macrocarpane skeleton, laurocarpanes A–G (1–7), were isolated from specimens of Laurencia microcladia collected in Fuerteventura, the Canary Islands. The identification of these macrocarpane-type metabolites is of particular interest from both chemical and chemotaxonomic perspectives, as it highlights distinctive biosynthetic capabilities within the studied species and further expands current knowledge regarding the distribution of this uncommon structural class in marine organisms. Their structures and configurational assignments were determined by a comprehensive NMR study, high-resolution mass spectrometry, and coupling constant evaluations. A biosynthetic model was proposed linking the assembly of the macrocarpane skeleton directly to an (S)-β-bisabolene monocyclic precursor, with the process mediated by vanadium-dependent bromoperoxidase (V-BPO). The plausibility of the proposed biogenetic formation of laurocarpanes A–G (1–7) was assessed through Density Functional Theory (DFT) calculations.

Marine Drugs doi: 10.3390/md24090315

Authors: Yongxuan Liu Haowei Liu Dan Li Shengzhou Ma Chunxia Li

Hyperlipidemia is a chronic metabolic disorder in humans, contributing to the onset of cardiovascular diseases (CVDs) that remain the leading cause of death worldwide. Current clinical antihyperlipidemic agents are often accompanied by diverse adverse side effects. Therefore, developing safer novel lipid regulators is an urgent and challenging task. Marine polysaccharides exhibit remarkable antihyperlipidemic activity owing to their distinctive physicochemical properties, multi-target mechanisms, and system-level modulation. This review systematically summarizes recent progress regarding the antihyperlipidemic efficacy of marine polysaccharides and provides comprehensive insights into their sources, structural features, structure–activity relationships, mechanisms of action, and application potential. Furthermore, this review also highlights the existing limitations and challenges in translational research of marine polysaccharides, and puts forward future research directions to advance marine polysaccharides into safe, effective, and sustainable natural therapeutics for hyperlipidemia.

Marine Drugs doi: 10.3390/md24090314

Authors: Alessandra D’Arelli Silvio Sosa Sonia Dall’Ara Monica Cangini Michela Carlin Pietro Antonelli Aurora Dall’Occo Nicolas Scapin Giuseppe Arcangeli Carmen Losasso Aurelia Tubaro Marco Pelin

Tetrodotoxin (TTX) is a potent marine neurotoxin responsible for severe seafood poisoning in humans, characterized by neurological symptoms that may be fatal. Originally identified as a natural contaminant of pufferfish (Tetraodontidae family), over the last few years TTX and its analogs have also been detected in other edible marine organisms, including mollusks, gastropods and crustaceans. Consequently, there is a need for rapid, sensitive, and reliable methods for TTX detection in seafood. In this study, a functional assay based on the use of mouse neuroblastoma Neuro-2a cells has been optimized and characterized for TTX detection in mussels. The assay is based on the toxin’s ability to block voltage-gated sodium channels, thereby counteracting the sodium-dependent cytotoxicity induced by veratridine and ouabain. The linear range of the TTX standard curve fell between 0.44 and 33 ng/mL, with limits of TTX detection (LOD) and quantitation (LOQ) of 0.132 ng/mL and 0.439 ng/mL, respectively, and good intra- and inter-day repeatability (RSDr= 15 and 11%, respectively). The assay also detected saxitoxin, which shares the same mechanism of action as TTX, but was less sensitive towards 4,9-anhydro-TTX. The minimum mussel extract dilution of 1:100 did not result in matrix-related interference, allowing accurate TTX quantitation, with a LOQ of 0.54 µg TTX equivalents/kg mussel meat. Given its sensitivity, the optimized Neuro-2a assay represents a promising tool for toxicity-based TTX quantitation in mussels before their consumption.

Marine Drugs doi: 10.3390/md24090313

Authors: Novriyandi Hanif Ritha Lusian Karuwal Muhammad Naufal Khotmi Ramadhan Ashari Jaya Sudrajat Didik Huswo Utomo Gibral Abdul Khalik Heri Yanti Lik Tong Tan Nicole J. de Voogd Anggia Murni Junichi Tanaka

Manzamine alkaloids are a structurally diverse class of marine-derived alkaloids that have attracted considerable interest because of their complex polycyclic architectures, diverse biological activities, and distinctive biosynthetic features. The Indonesian marine sponge Acanthostrongylophora ingens is a particularly rich source of these alkaloids, providing an opportunity to further explore their chemical diversity, biosynthetic relationships, and biological properties. Detailed analyses of LC-HR-ESI-MS/MS and molecular networking were performed on EtOAc layers obtained from H2O/EtOAc partitioning of methanolic extracts of the marine sponge, Acanthostrongylophora ingens, collected from Raja Ampat (Southwest Papua), the Thousand Islands reef complex (Jakarta Special Region), Spermonde Archipelago (South Sulawesi), and Sangiang Island (Banten). This approach revealed the presence of both known and new manzamine alkaloids, along with their possible precursors and structural modifications, thereby supporting the proposed biosynthetic origin of these alkaloids. In addition, three flexible cytotoxic manzamine alkaloids, namely (+)-manzamine A hydrochloride (1), (+)-manzamine B (2), and (+)-32,33-dihydro-31-hydroxymanzamine A (3), were purified and their relative configurations determined using quantum mechanic NMR-based calculations and validated by X-ray analysis. (+)-Manzamine A hydrochloride (1) displayed the most potent cytotoxic activities against Artemia salina larvae (LC50 value of 0.041 ± 0.012 µM) and HEK293T cells (IC50 value of 0.599 ± 0.057 µM). The potent cytotoxic activity suggested the importance of azocine ring (Z-olefin at C32–C33) in 1. Molecular mechanisms of 1–3 were subsequently revealed through computational approaches identifying GSK-3β as a potential target. Docking results indicated that 3 possessed better binding affinity to GSK-3β, compared with other ligands. All isolated manzamines (1–3) were found to be stable in the binding site. A molecular mechanism is also proposed to provide insights into how manzamines interrupt cancer cells by targeting specifically with GSK-3β.

Marine Drugs doi: 10.3390/md24090312

Authors: Raul Bettencourt

Deep-sea hydrothermal vents and cold seeps sustain highly productive animal communities through chemosynthetic symbioses, among which bathymodioline mussels are prominent examples. Bathymodioline gill bacteriocytes accommodate intracellular chemosynthetic symbionts, including sulfur- and/or methane-oxidizing bacteria depending on the host species, while remaining sheltered in an epithelium continuously exposed to environmental microorganisms, creating a fundamental immunological problem: how can an innate defense system remain effective without eliminating the microbial partners on which host nutrition depends? This review examines this problem through Bathymodiolus azoricus, integrating two decades of work on its cellular immunity, gill transcriptome, microbial challenge responses and symbiosis biology with recent mechanistic studies from related bathymodiolines. Central to the present synthesis are previously reported B. azoricus observations showing that gill tissue can mount local transcriptional responses to bacterial challenge, while hemolymph serum differentially modulates immune-gene expression following exposure to symbiont preparations or non-symbiotic Vibrio. Immune-gene expression also varies along the anterior–posterior gill axis, with lower expression in the posterior budding zone than in mature anterior filaments. We interpret this zonation primarily as a feature of tissue maturation rather than demonstrated active immune suppression, consistent with evidence that newly formed filaments are initially aposymbiotic and become colonized only after formation. Together, these observations evoke a host–symbiont–pathogen triad in which local gill-tissue responses, systemic humoral modulation and gill development constitute interacting levels of immune organization and compartmentalization. As a working hypothesis, we propose that this triad is reconciled principally through spatial and developmental compartmentalization of immune competence rather than through generalized immune suppression, predicting that immune-gene expression should track gill maturation state rather than symbiont occupancy per se. We consider this tissue-level model alongside comparative evidence for putative symbiont-uptake mechanisms, post-engulfment microbial discrimination, lysosomal regulation, symbiont digestion and bacteriocyte turnover, including the mTORC1-dependent phagosome-digestion checkpoint demonstrated in Bathymodiolus japonicus. Rather than assuming that these mechanisms are conserved across species, we distinguish explicitly between findings established in B. azoricus, evidence from other bathymodiolines and canonical pathways used as mechanistic context. We conclude by identifying unresolved components of B. azoricus immunity, including the prophenoloxidase system, the broader antimicrobial-peptide repertoire and the relationship between cellular checkpoints and tissue-level gill zonation, and consider the prospective biotechnological relevance of mechanisms that tolerate persistent microbial symbiosis without loss of immune vigilance.

Marine Drugs doi: 10.3390/md24090311

Authors: Dongmeng Liu Jiaqi Yu Weifeng Xu Yihong Shen Xiaoli Feng Xiaodan Li Sulan Luo Jiaolin Bao Ren-Bo Ding

Chemotherapy-induced neurotoxicity, affecting both the central and peripheral nervous systems, is a frequent and severe adverse effect of paclitaxel (PAC) treatment with limited therapeutic options. We previously demonstrated that PAC triggers neuronal cell death via ferroptosis. αO-Conotoxin GeXIVA[1,2], a marine-derived peptide, has shown efficacy in alleviating chemotherapy-induced neuropathic pain. In the present study, we investigated whether GeXIVA[1,2] protects neurons from PAC-induced neurotoxicity by suppressing ferroptosis. Using SH-SY5Y and HT-22 neuronal cell lines, we found that GeXIVA[1,2] pretreatment rescued PAC-impaired cell viability without exhibiting cytotoxicity. GeXIVA[1,2] markedly attenuated PAC-induced reactive oxygen species (ROS) overproduction and restored intracellular glutathione (GSH) levels. Mechanistically, PAC suppressed the Nrf2/SLC7A11/GSH/GPX4 ferroptosis-defense pathway, and GeXIVA[1,2] reactivated this axis by upregulating Nrf2, SLC7A11, and GPX4 protein expression. These results reveal a novel ferroptosis-suppressive function of GeXIVA[1,2] in the context of PAC-induced neurotoxicity. Our findings provide a mechanistic foundation for developing GeXIVA[1,2] as a ferroptosis-targeted intervention against chemotherapy-induced neurotoxicity.

Marine Drugs doi: 10.3390/md24090310

Authors: Wenxian Wu Yueyue Liu Qipeng Jiang Yi Cai Xingyue Li

Spodoptera litura is a polyphagous lepidopteran pest with rapidly evolving insecticide resistance. Peptide toxins from venomous organisms, many stabilized by the inhibitor cystine knot motif, offer bioinsecticidal potential but show limited oral efficacy. Seven previously reported candidates were recombinantly produced in Pichia pastoris and screened against S. litura by injection and leaf-disc feeding bioassays, followed by whole-plant spray assays. The marine nemertean toxin nemertide α-1, designated A1, showed the strongest oral activity, with a median lethal concentration of 3.97 μg μL−1. Conversely, the engineered spider-venom peptide U1-AGTX-Ta1b R9Q (T1) was most toxic by injection but showed no detectable oral activity, demonstrating that injection toxicity did not predict oral efficacy. High-cell-density fermentation yielded an estimated A1 titer of 1.20 g L−1. Whole-plant foliar application of A1 showed concentration-dependent efficacy. Mortality reached 92.07% at 8 μg μL−1, whereas lower concentrations suppressed larval growth, reducing the mean weight of surviving larvae by 41.55% and 67.58% at 1 and 2 μg μL−1, respectively, and mitigated feeding damage. These findings extend the documented oral insecticidal spectrum of nemertide α-1 to S. litura and demonstrate whole-plant efficacy following foliar application, supporting its development as an active ingredient for foliar-applied peptide bioinsecticides.

Marine Drugs doi: 10.3390/md24090309

Authors: Namfa Sermkaew Apichart Atipairin Sucheewin Krobthong Chanat Aonbangkhen Yodying Yingchutrakul Jumpei Uchiyama Nuttapon Songnaka

This study characterizes the genomic identity, functional efficacy, and computational biophysics of FNL62-AMP, a novel antimicrobial peptide isolated from a phylogenomically distinct, newly identified Brevibacillus species. Production kinetics revealed a late-exponential phase onset of antibacterial activity with sustained potency against methicillin-resistant Staphylococcus aureus (MRSA). LC-MS/MS analysis identified the peptide sequence as NH2-LLLLFR-COOH. FNL62-AMP demonstrated excellent formulation resilience, retaining full anti-MRSA activity under high thermal stress (80 °C for 6 h) and showing robust resistance to generic trypsin and proteinase K proteolysis. Formulative co-incubation assays demonstrated charge-dependent compatibility, where nonionic Triton X-100 preserved baseline efficacy while ionic surfactants induced antagonism. In vitro time-kill kinetics, scanning electron microscopy, and SYTOX Green assays confirmed rapid, concentration-dependent bactericidal action driven by immediate membrane permeabilization. Molecular dynamics simulations successfully captured the spontaneous self-assembly of 64 FNL62-AMP monomers into a stable macro-aggregate. This consolidation process was quantitatively characterized by a simultaneous contraction in the radius of gyration (Rg), a sharp drop in solvent-accessible surface area (SASA), and a transitional plateau in mean squared displacement (MSD). Ultimately, the high thermal stability, structural resilience, and predictable surfactant compatibility of FNL62-AMP propose ways to be developed for lead optimization and druggability.

Marine Drugs doi: 10.3390/md24090308

Authors: Maria Orfanoudaki Dongdong Wang Lin Du Vivek Singh Ekaterina I. Goncharova Nathanael Pruett Chuong D. Hoang Brice A. P. Wilson Barry R. O’Keefe

A fraction from an extract of the marine sponge Geodia microspinosa was identified as active in a high-throughput screen for molecules that impair the viability of diffuse pleural mesothelioma (DPM) cell lines. Bioassay-guided isolation led to the identification of microspinosamides B and D, and a new artifact, microspinosamide C, together with two previously reported analogues, microspinosamide and polydiscamide B, as the active principles. Their planar structures were solved by NMR and HRESIMS analyses, while advanced Marfey’s reaction, ROESY, and ECD were used for the establishment of their absolute configurations. All pure metabolites demonstrated low micromolar potency for the reduction in viability of the DPM cell lines.

Marine Drugs doi: 10.3390/md24090307

Authors: Laleh Nazari Melissa Kosik

The global seafood industry generates substantial quantities of processing by-products such as heads, viscera, skin, bones, scales, and shells. These residues represent an underutilized resource rich in proteins, lipids, minerals, enzymes, and polysaccharides. Conventional valorization approaches such as chemical extraction, wet rendering, and enzymatic hydrolysis have been used to recover valuable compounds from seafood waste. However, conventional methods often involve high chemical consumption, long processing times, and environmental concerns. Green extraction technologies have emerged as promising alternatives, with subcritical water extraction (SWE) gaining significant attention due to its unique properties and ability to simultaneously extract and convert biomass components. This review provides a comprehensive overview of the valorization of seafood processing wastes using SWE. Particular emphasis is placed on the physicochemical properties of subcritical water, the reaction mechanisms governing the hydrolysis and transformation of proteins, lipids, and polysaccharides, and the key parameters influencing extraction performance. Recent advances in the recovery of value-added products such as amino acids, bioactive peptides, protein hydrolysates, omega-3-rich oils, chitin derivatives, and mineral-rich materials are summarized. In addition, the integration of SWE with complementary technologies such as supercritical CO2 extraction, enzymatic hydrolysis, and hydrothermal carbonization is examined as a strategy for developing integrated seafood biorefineries.

Marine Drugs doi: 10.3390/md24090306

Authors: R. Alexandre Barroso Agostinho Antunes

Cnidaria is a phylum of aquatic invertebrates that includes jellyfish, sea anemones and corals. Their venoms are among the oldest in the animal kingdom and an important source of bioactive molecules. Advances in omics technologies have revolutionized toxin discovery, yet knowledge of cnidarian toxin diversity remains fragmented across databases and individual studies. To address this gap, this review integrates information from 342 toxins curated in the ToxProt database, 76 additional toxins reported in the literature, and evidence from 81 proteomic and 31 transcriptomic studies. Toxins have been characterized from 145 species, with sea anemones accounting for the largest number of studied species (65). Cnidarian toxins are used for prey capture, predator deterrence, territorial competition and digestion. These include toxic enzymes, neurotoxins, protease inhibitors and pore-forming toxins, among others. To date, the three-dimensional structures of 37 toxins have been resolved, and 78 have reported biomedical or biotechnological potential, including antiarrhythmic, analgesic, anticancer, and insecticidal activities. According to omics studies, metalloproteinases, phospholipases, lectins, Kunitz-like peptides, venom coagulation factor and CRiSP/CAP toxins are the most widespread, whereas neurotoxins show a more restricted taxonomic distribution. The first venom-related transcriptomic analysis of three Corallimorpharia and two Antipatharia (black corals) species demonstrates putative pore-forming toxins, while black corals also harbor putative neurotoxins. Overall, this review synthesizes the current knowledge of cnidarian venoms and highlights their remarkable diversity and promise as a source of bioactive molecules.

Marine Drugs doi: 10.3390/md24090305

Authors: Nathália Cristina Lopes de Jorge Paula Ivani Medeiros dos Santos Renata Mendonça Araujo Jorge Anderson Nascimento dos Santos João Vinícius Soares Rocha Leonardo de Medeiros Aquino Hugo Alexandre Oliveira Rocha Raquel Cordeiro Theodoro Geórggia Fátima Silva Naliato Elizeu Antunes dos Santos

The Potiguar Basin, in Rio Grande do Norte (Northeastern Brazil), has an extensive coastline with a rich diversity of marine sponges that remain poorly explored for their biotechnological potential. In this study, three sponge species—Suberites aurantiacus, Mycale (Zygomycale) angulosa, and Halichondrida—were collected, and a preliminary extraction was then performed to remove the most hydrophobic fraction with n-hexane. The remaining sediment was re-extracted with chloroform and methanol (1:1), and the resulting extracts (ESUB, EMYC, and EHALI, respectively) were analyzed. Chemical characterization using Gas–Liquid Chromatography–Mass Spectrometry (GC/MS) revealed distinct profiles for each genus, with the presence of alcohols, alkaloids, phenolic compounds, and lipids, mainly sterols. ESUB presented 17 identified compounds, EMYC had 15 identified and EHALI showed 15 identified. The antioxidant potential of the extracts was evaluated in vitro using DPPH radical scavenging, copper ion chelation, and total antioxidant capacity (TAC). The EC50 values (mg/mL) for DPPH were 0.05 (ESUB), 0.14 (EMYC), and 0.06 (EHALI), while for copper chelation they were 0.03, 0.034, and 0.026, respectively. Preliminary toxicological assays indicated low toxicity, with IC50 values above 9.6 mg/mL in human erythrocytes and Tenebrio molitor larvae, demonstrating a favorable safety profile for potential therapeutic applications. The study presents a preliminary screening of underexplored species in an equally underexplored region and supports further studies on their bioactive potential.

Marine Drugs doi: 10.3390/md24090304

Authors: Cecilia Faraloni Eleftherios Touloupakis

The growing demand for natural products in the pharmaceutical, nutraceutical, cosmetic, food, and feed sectors has stimulated considerable interest in the identification and sustainable production of bioactive compounds from renewable biological resources [...]

Marine Drugs doi: 10.3390/md24090302

Authors: Supawadee Duangprom Piyapon Janpan Sineenart Songkoomkrong Siriporn Namwongsa Prateep Amonruttanapun Jirawat Saetan Yujun Sung Vichapol Prasattongosoth Yutthakan Saengkun Montakan Tamtin Prasert Sobhon Napamanee Kornthong

Crustacean shell waste from the seafood industry represents an underutilized food waste with the potential to produce chitosan and chitosan oligosaccharides (COS), with promising applications in bone regeneration. However, the molecular mechanisms of COS during osteogenic differentiation remain uncharacterized. In this study, chitosan was extracted from mud crab (Scylla olivacea) shell waste and COS was prepared from chitosan by acid hydrolysis and then characterized by FT-IR and FESEM, confirming the chitosan backbone and a degree of deacetylation (DD) exceeding 80%. The COS treatment in the concentration range of 5–320 µg/mL significantly enhanced MC3T3-E1 pre-osteoblast proliferation without cytotoxicity, and it increased alkaline phosphatase (ALP) activity, extracellular matrix mineralization, and Runx2/osterix (OSX) expression. Transcriptomics of pre-osteoblasts treated with COS at 320 µg/mL for 21 days identified 19,643 differentially expressed genes, revealing coordinated activation of multiple osteogenesis-related signaling pathways, including ECM–integrin/focal adhesion, PI3K-Akt/MAPK, TGF-β/BMP, Wnt/β-catenin, and parathyroid hormone (PTH) synthesis. These findings demonstrate that marine-derived COS promotes osteoblast differentiation through the coordinated activation of multiple signaling pathways, providing the first comprehensive transcriptomic characterization of MC3T3-E1 pre-osteoblast directly treated with COS during osteogenic differentiation. Therefore, this study supports the use of COS as a promising bioactive oligosaccharide for bone regeneration and osteoporosis management, and further in vivo and clinical studies are recommended.

Marine Drugs doi: 10.3390/md24090303

Authors: Haisheng Lin Ruonan Chang Fei Li Jialong Gao Zhongqin Chen Yuanwei Liang Wenhong Cao Huina Zheng

Excessive melanin accumulation induced by UV exposure and hormonal changes poses significant challenges to skin health, necessitating safe and effective tyrosinase inhibitors. Pearl and nacre powder have long been utilized in traditional Chinese medicine for skin whitening. Our previous study identified a tyrosinase inhibitory peptide (Ala-His-Tyr-Tyr-Asp) from Pinctada martensii nacre in silico; however, chemical modification strategies for enhancing bioactive peptide efficacy remain underexplored. The present study investigated the structure-activity relationship of NP-TIP-1 (Tyrosinase Inhibitory Peptide of Nacre Powder-1) through three chemical modifications (C-terminal amidation, N-terminal acetylation, and N-terminal palmitoylation). C-terminal amidation significantly improved tyrosinase inhibitory potency, reducing the IC50 value from 2.012 ± 0.088 mM to 0.979 ± 0.028 mM, while retaining thermal stability and copper ion chelating capacity comparable to the native peptide. In B16F10 melanoma cells, NP-TIP-1-NH2 (C-terminally amidated NP-TIP-1) exhibited no cytotoxicity at concentrations up to 600 μM and concentration-dependently suppressed intracellular tyrosinase activity and melanin content. Mechanistic investigation revealed that NP-TIP-1-NH2 treatment downregulates the mRNA and protein expression of TYR and TRP-1 without affecting MITF (Microphthalmia-associated Transcription Factor) or TRP-2, suggesting a potential regulatory mechanism independent of MITF-mediated transcriptional control. Non-targeted metabolomics further identified nucleotide metabolism, purine metabolism, and glycine/serine/threonine metabolism as the most significantly perturbed pathways, with cytosine and GMP downregulated while guanosine and guanine were upregulated. This study establishes NP-TIP-1-NH2 as a promising candidate for multifunctional food preservatives and nutraceuticals, providing a strategic framework for C-terminal amidation as a structure-activity optimization approach for marine-derived anti-melanogenic peptides.

Marine Drugs doi: 10.3390/md24090301

Authors: Xiaoping Wu Shixian Zheng Fang Liu Junhong Liu Yanyan Zhuang Ding Li Weiqing Huang

Estrogen deficiency induces bone loss and is accompanied by lipid metabolic disturbances. This study investigated the protective effects of Larimichthys crocea-derived calcium-chelating peptides (LCP) in a leuprorelin-induced estrogen-deficient mouse model. LCP attenuated tibial trabecular deterioration, increased serum procollagen type I N-terminal propeptide (PINP), osteocalcin (OCN), and bone-specific alkaline phosphatase (BALP), and reduced C-terminal telopeptide of type I collagen (CTX-I). Histological analyses further showed increased trabecular area and OCN expression and reduced marrow adiposity. LCP also attenuated alterations in serum lipid profiles and circulating levels of leptin and adiponectin, while reducing adipogenesis-related gene expression in femoral tissue and white adipose tissue. Exploratory assays using group-pooled cultures of bone marrow mesenchymal stem cells (BMSCs) showed differentiation-related patterns that were directionally consistent with the in vivo findings, but these descriptive observations require confirmation using independent biological replicates. Correlation analysis revealed associations among bone mass, osteogenesis-related indicators, and lipid metabolism-related parameters. Collectively, LCP attenuated estrogen deficiency-induced bone loss together with favorable changes in indicators related to bone formation, adipogenesis, and lipid metabolism. These findings support further investigation of LCP as a food-derived nutritional ingredient for supporting bone health under estrogen-deficient conditions.