Marine Drugs

Barnacles, a prevalent fouler organism in intertidal zones, has long been a source of annoyance due to significant economic losses and ecological impacts. Numerous antifouling approaches have been explored, including extensive research on antifouling chemicals. However, the excessive utilization of small-molecule chemicals appears to give rise to novel environmental concerns. Therefore, it is imperative to develop new strategies. Barnacles exhibit appropriate responses to environmental challenges with complex physiological processes and unique sensory systems. Given the assumed crucial role of bioactive peptides, an increasing number of peptides with diverse activities are being discovered in barnacles. Fouling-related processes have been identified as potential targets for antifouling strategies. In this paper, we present a comprehensive review of peptides derived from barnacles, aiming to underscore their significant potential in the quest for innovative solutions in biofouling prevention and drug discovery. Full article

Krill oil (KO) shows promise as a natural marine-derived ingredient for improving skin health. This study investigated its antioxidant, anti-inflammatory, anti-wrinkle, and moisturizing effects on skin cells and UVB-induced skin photoaging in hairless mice. In vitro assays on HDF, HaCaT, and B16/F10 cells, as well as in vivo experiments on 60 hairless mice were conducted. A cell viability assay, diphenyl-1-picryhydrazyl (DPPH) radical scavenging activity test, elastase inhibition assay, procollagen content test, MMP-1 inhibition test, and hyaluronan production assay were used to experiment on in vitro cell models. Mice received oral KO administration (100, 200, or 400 mg/kg) once a day for 15 weeks and UVB radiation three times a week. L-Ascorbic acid (L-AA) was orally administered at 100 mg/kg once daily for 15 weeks, starting from the initial ultraviolet B (UVB) exposures. L-AA administration followed each UVB session (0.18 J/cm²) after one hour. In vitro, KO significantly countered UVB-induced oxidative stress, reduced wrinkles, and prevented skin water loss by enhancing collagen and hyaluronic synthesis. In vivo, all KO dosages showed dose-dependent inhibition of oxidative stress-induced inflammatory photoaging-related skin changes. Skin mRNA expressions for hyaluronan synthesis and collagen synthesis genes also increased dose-dependently after KO treatment. Histopathological analysis confirmed that krill oil (KO) ameliorated the damage caused by UVB-irradiated skin tissues. The results imply that KO could potentially act as a positive measure in diminishing UVB-triggered skin photoaging and address various skin issues like wrinkles and moisturization when taken as a dietary supplement. Full article

Marine algae are sources of bioactive components with defensive properties of great value against microbial infections. This study investigated the bioactivity of extracts from brown algae Fucus vesiculosus against rotavirus, the worldwide leading cause of acute gastroenteritis in infants and young children. Moreover, one of the extracts was tested against four foodborne bacteria: Campylobacter jejuni, Escherichia coli, Salmonella Typhimurium, and Listeria monocytogenes, and the non-pathogenic: E. coli K12. In vitro tests using MA104 cells revealed that both whole algae extracts and crude fucoidan precipitates neutralized rotavirus in a dose-responsive manner. The maximum neutralization activity was observed when the rotavirus was incubated with 100 μg mL⁻¹ of the hydrochloric acid-obtained crude fucoidan (91.8%), although crude fucoidan extracted using citric acid also demonstrated high values (89.5%) at the same concentration. Furthermore, molecular weight fractionation of extracts decreased their antirotaviral activity and high molecular weight fractions overall exhibited higher activity compared to those of lower molecular weight. A seaweed extract with high antirotaviral activity was also found to inhibit the growth of C. jejuni, S. Typhimurium, and L. monocytogenes at a concentration of 0.2 mg mL⁻¹. Overall, this study expands the current knowledge regarding the antimicrobial mechanisms of action of extracts from F. vesiculosus. Full article

Anserine is a naturally occurring histidine dipeptide with significant antioxidant activities. This study aimed to investigate the preventive mechanism of anserine on tert-butyl hydroperoxide (TBHP)-induced liver damage in a normal human liver cell line (L-02 cells). The L-02 cells were pretreated with anserine (10, 20, and 40 mmol/L) and then induced with 400 μmol/L of TBHP for 4 h. The results showed that the survival rates of L-02 cells and the contents of GSH were significantly increased with the pretreatment of anserine; the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the extracellular fluid were sharply decreased; and the formation of reactive oxygen species (ROS), nuclear fragmentation, and apoptosis were significantly inhibited. In addition, anserine could bind to the Kelch domain of Kelch-like ECH-associated protein 1 (Keap1) with a binding force of −7.2 kcal/mol; the protein expressions of nuclear factor-erythroid 2-related factor-2 (Nrf2), quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), and Bcl-2 were upregulated by anserine in TBHP-induced L-02 cells, with the downregulation of p-JNK and caspase-3. In conclusion, anserine might alleviated liver injury in L-02 cells via regulating related proteins in the Keap1-Nrf2 and JNK-Caspase-3 signaling pathways. Full article

Secondary metabolites—organic compounds that are often bioactive—produced by endophytes, among others, provide a selective advantage by increasing the organism’s survivability. Secondary metabolites mediate the symbiotic relationship between endophytes and their host, potentially providing the host with tolerance to, and protection against biotic and abiotic stressors. Secondary metabolites can be secreted as a dissolved substance or emitted as a volatile. In a previous study, we isolated bioactive endophytes from several macroalgae and tested them in vitro for their ability to inhibit major disease-causing pathogens of aquatic animals in the aquaculture industry. One endophyte (isolate Abp5, K. flava) inhibited and killed, in vitro, the pathogen Saprolegnia parasitica, an oomycete that causes saprolegniasis—a disease affecting a wide range of aquatic animals. Here, using analytical chemistry tools, we found that Abp5 produces the volatile organic compound (VOC) 8-nonenoic acid. Once we confirmed the production of this compound by the endophyte, we tested the compound’s ability to treat S. parasitica in in vitro and in vivo bioassays. In the latter, we found that 5 mg/L of the compound improves the survival of larvae challenged with S. parasitica by 54.5%. Our isolation and characterization of the VOC emitted by the endophytic K. flava establish the groundwork for future studies of endophytic biocontrol agents from macroalgae. Use of this compound could enable managing oomycete agricultural pathogens in general, and S. parasitica in particular, a major causal agent in aquaculture diseases. Full article

Fish-derived collagen hydrolysate (CH) has shown promise in improving hair and skin health. Therefore, this study sought to comprehensively assess the effects of CH extracted from Mozambique tilapia (Oreochromis mossambicus) scales on hair and skin using in vitro and in vivo models. Human dermal papilla cells (hDPCs) were used for antioxidant and gene expression analyses, while C57BL/6 mice were orally administered CH for six weeks to assess hair growth patterns. The mice were divided into four groups: negative control (NC; distilled water), positive control (PC; 1 mg/kg finasteride), CH500 (500 mg/kg BW CH), and CH1000 (1000 mg/kg BW CH). CH mitigated catalase activity reduction in hDPCs, increased IGF-1 and VEGF levels, and decreased TGF-β1, TNF-α, and IL-1β expression. In vivo, CH treatment improved hair growth index, length, diameter, weight, and density. Scanning electron microscopy revealed reduced hair damage. Moreover, CH up-regulated IGF-1, VEGF, Elastin, and HAS2 mRNA expression while down-regulating TNF-α and IL-1β. CH enhanced hair shine, growth, and skin health while alleviating inflammation. These findings demonstrate the potential of CH in alleviating oxidative stress, promoting hair growth, and enhancing skin health, both in vitro and in vivo. Fish-derived CH offers a cost-effective and bioavailable option for improving hair and skin health. Full article

A library of naturally occurring and semi-synthetic discorhabdins was assessed for their effects on Merkel cell carcinoma (MCC) cell viability. The set included five new natural products and semi-synthetic compounds whose structures were elucidated with NMR, HRMS, and ECD techniques. Several discorhabdins averaged sub-micromolar potency against the MCC cell lines tested and most of the active compounds showed selectivity towards virus-positive MCC cell lines. An investigation of structure–activity relationships resulted in an expanded understanding of the crucial structural features of the discorhabdin scaffold. Mechanistic cell death assays suggested that discorhabdins, unlike many other MCC-active small molecules, do not induce apoptosis, as shown by the lack of caspase activation, annexin V staining, and response to caspase inhibition. Similarly, discorhabdin treatment failed to increase MCC intracellular calcium and ROS levels. In contrast, the rapid loss of cellular reducing potential and mitochondrial membrane potential suggested that discorhabdins induce mitochondrial dysfunction leading to non-apoptotic cell death. Full article

Bone tissue engineering is a promising treatment for bone loss that requires a combination of porous scaffold and osteogenic cells. The aim of this study was to evaluate and develop a tricomposite, biomimetic scaffold consisting of marine-derived biomaterials, namely, chitosan and fucoidan with hydroxyapatite (HA). The effects of chitosan, fucoidan and HA individually and in combination on the proliferation and differentiation of human mesenchymal stem cells (MSCs) were investigated. According to the SEM results, the tricomposite scaffold had a uniform porous structure, which is a key requirement for cell migration, proliferation and vascularisation. The presence of HA and fucoidan in the chitosan tricomposite scaffold was confirmed using FTIR, which showed a slight decrease in porosity and an increase in the density of the tricomposite scaffold compared to other formulations. Fucoidan was found to inhibit cell proliferation at higher concentrations and at earlier time points when applied as a single treatment, but this effect was lost at later time points. Similar results were observed with HA alone. However, both HA and fucoidan increased MSC mineralisation as measured by calcium deposition. Differentiation was significantly enhanced in MSCs cultured on the tricomposite, with increased alkaline phosphatase activity on days 17 and 25. In conclusion, the tricomposite is biocompatible, promotes osteogenesis, and has the structural and compositional properties required of a scaffold for bone tissue engineering. This biomaterial could provide an effective treatment for small bone defects as an alternative to autografts or be the basis for cell attachment and differentiation in ex vivo bone tissue engineering. Full article

(1) Background: Microalgae are promising feedstock for obtaining valuable bioactive compounds. To facilitate the release of these important biomolecules from microalgae, effective cell disruption is usually necessary, where the use of ultrasound has achieved considerable popularity as an alternative to conventional methods. (2) Methods: This paper aims to evaluate the use of ultrasound technology in water medium as a green technology to recover high added-value compounds from Dunaliella salina and improve its sensory profile towards a high level of incorporation into novel food products. (3) Results: Among the variables, the solid concentration and extraction time have the most significant impact on the process. For the extraction of protein, or fat, the most influential factor is the extraction time. Total polyphenols are only significantly affected by the extraction time. The antioxidant capacity is strongly affected by the solid to liquid ratio and, to a small extent, by the extraction time. Ultrasound-assisted extraction improves the overall odor/aroma of D. salina with good acceptability by the panelists. (4) Conclusions: The application of ultrasonic-assisted extraction demonstrates a positive overall effect on enhancing the sensory profile, particularly the odor of microalgal biomass, while the bioactive properties are preserved. Notably, the intense sea/fish odors are reduced, while earthy and citrus notes become more prominent, resulting in an improved overall sensory profile score. This is the first time, to our knowledge, that this innovative, green, and efficient technology has been used to upgrade the aroma profile of microalgae. Full article

In the present study, the recovery of valuable molecules of proven anti-inflammatory and antimicrobial activity of the acidophilic microalga Coccomyxa onubensis (C. onubensis) were evaluated using green technologies based on ultrasound-assisted extraction (UAE). Using a factorial design (3 × 2) based on response surface methodology and Pareto charts, two types of ultrasonic equipment (bath and probe) were evaluated to recover valuable compounds, including the major terpenoid of C. onubensis, lutein, and the antimicrobial activity of the microalgal extracts obtained under optimal ultrasound conditions (desirability function) was evaluated versus conventional extraction. Significant differences in lutein recovery were observed between ultrasonic bath and ultrasonic probe and conventional extraction. Furthermore, the antimicrobial activity displayed by C. onubensis UAE-based extracts was greater than that obtained in solvent-based extracts, highlighting the effects of the extracts against pathogens such as Enterococcus hirae and Bacillus subtilis, followed by Staphylococcus aureus and Escherichia coli. In addition, gas chromatography–mass spectrometry was performed to detect valuable anti-inflammatory and antimicrobial biomolecules present in the optimal C. onubensis extracts, which revealed that phytol, sterol-like, terpenoid, and even fatty acid structures could also be responsible for the antibacterial activities of the extracts. Moreover, UAE displayed a positive effect on the recovery of valuable molecules, improving biocidal effects. Our study results facilitate the use of green technology as a good tool in algal bioprocess engineering, improving energy consumption and minimizing environmental impacts and process costs, as well as provide a valuable product for applications in the field of biotechnology. Full article

The carotenoids mixture (MC) isolated from the starfish Patiria. pectinifera contains more than 50% astaxanthin, 4–6% each zeaxanthine and lutein, and less pharmacologically active components such as free fatty acids and their glycerides. Astaxanthin, the major component of MC, belongs to the xanthophyll class of carotenoids, and is well known for its antioxidant properties. In this work, in vitro and in vivo studies on the biological activity of MC were carried out. The complex was shown to exhibit anti-inflammatory, anti-allergic and cancer-preventive activity, without any toxicity at a dose of 500 mg/kg. MC effectively improves the clinical picture of the disease progressing, as well as normalizing the cytokine profile and the antioxidant defense system in the in vivo animal models of inflammatory diseases, namely: skin carcinogenesis, allergic contact dermatitis (ACD) and systemic inflammation (SI). In the skin carcinogenesis induced by 7,12-dimethylbenzanthracene, the incidence of papillomas was decreased 1.5 times; 1% MC ointment form in allergic contact dermatitis showed an 80% reduced severity of pathomorphological skin manifestations. Obtained results show that MC from starfish P. pectinifera is an effective remedy for the treatment and prevention of inflammatory processes. Full article

The protein extract of Ulva australis hydrolyzed with Alcalase and Flavourzyme was found to have multi-functional properties, including total antioxidant capacity (TAC), collagenase inhibitory, and antibacterial activities. The #5 fraction (SP5) and #7 fraction (SP7) of U. australis hydrolysate from cation-exchange chromatography displayed significantly high TAC, collagenase inhibitory, and antibacterial effects against Propionibacterium acnes, and only the Q3 fraction from anion-exchange chromatography displayed high multi-functional activities. Eight of 42 peptides identified by MALDI-TOF/MS and Q-TOF/MS/MS were selected from the results for screening with molecular docking on target proteins and were then synthesized. Thr-Gly-Thr-Trp (TGTW) displayed ABTS [2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)] radical scavenging activity. The effect of TAC as Trolox equivalence was dependent on the concentration of TGTW. Asn-Arg-Asp-Tyr (NRDY) and Arg-Asp-Arg-Phe (RDRF) exhibited collagenase inhibitory activity, which increased according to the increase in concentration, and their IC₅₀ values were 0.95 mM and 0.84 mM, respectively. Peptides RDRF and His-Ala-Val-Tyr (HAVY) displayed anti-P. Acnes effects, with IC₅₀ values of 8.57 mM and 13.23 mM, respectively. These results suggest that the U. australis hydrolysate could be a resource for the application of effective nutraceuticals and cosmetics. Full article

Ascophyllum nodosum, a brown algae abundantly found along the North Atlantic coast, is recognized for its high polysaccharide content. In this study, we investigated the anti-hyperlipidemic effect of fucoidans derived from A. nodosum, aiming to provide information for their potential application in anti-hyperlipidemic therapies and to explore comprehensive utilization of this Iceland brown seaweed. The crude fucoidan prepared from A. nodosum was separated using a diethylethanolamine column, resulting in two fucoidan fractions, AFC-1 and AFC-2. Both fractions were predominantly composed of fucose and xylose. AFC-1 exhibited a higher sulfate content of 27.8% compared to AFC-2 with 17.0%. AFC-2 was primarily sulfated at the hydroxy group of C2, whereas AFC-1 was sulfated at both the hydroxy groups of C2 and C4. To evaluate the anti-hyperlipidemic effect, a hyperlipidemia mouse model was established by feeding mice a high-fat diet. The effects of AFC-1, AFC-2, and the crude extract were investigated, with the drug atorvastatin used as a positive comparison. Among the different fucoidan fractions and doses, the high dose of AFC-2 administration demonstrated the most significant anti-hyperlipidemic effect across various aspects, including physiological parameters, blood glucose levels, lipid profile, histological analysis, and the activities of oxidative stress-related enzymes and lipoprotein-metabolism-related enzymes (p < 0.05 for the final body weight and p < 0.01 for the rest indicators, compared with the model group), and its effect is comparable to the atorvastatin administration. Furthermore, fucoidan administration resulted in a lower degree of loss in gut flora diversity compared to atorvastatin administration. These findings highlight the significant biomedical potential of fucoidans derived from A. nodosum as a promising therapeutic solution for hypolipidemia. Full article

Background: The use of conventional astaxanthin extraction methods, typically involving organic solvents, leads to a heightened environmental impact. The aim of this study was to explore the potential use of environmentally friendly extraction solvents, such as vegetable oils, for recovering the shrimp by-product astaxanthin. Methods: Ultrasound-assisted extraction (UAE) in vegetable oils, including olive oil (OO), sunflower oil (SO), and flaxseed oil (FO), was employed to extract astaxanthin. The astaxanthin antioxidant activity was evaluated using an ABTS assay, and a mixture of gum Arabic and soy lecithin was used to form coacervates to produce astaxanthin encapsulation. Results: A by-product–vegetable oil ratio of 1:60, extraction time of 210 min, 60% amplitude of the extraction process, and the use of OO as the extracting medium resulted in an astaxanthin yield of 235 ± 4.07 μg astaxanthin/g by-products. The astaxanthin encapsulation efficiency on day 0 and astaxanthin recovery on day 1 were recorded at 66.6 ± 2.7% and 94.4 ± 4.6%, respectively. Conclusions: The utilization of OO as an extraction solvent for astaxanthin from shrimp by-products in UAE represents a novel and promising approach to reducing the environmental impact of shrimp by-products. The effective astaxanthin encapsulation efficiency highlights its potential application in food industries. Full article

An analysis of the lipidome of the brown alga Undaria pinnatifida (Laminariales) was performed’ more than 900 molecular species were identified in 12 polar lipids and 1 neutral lipid using HPLC/MS-MS. The seasonal changes of U. pinnatifida lipidome were determined. It was shown that acclimatization to winter and spring was accompanied by an increase in the unsaturation of both polar and neutral lipids. In autumn and summer, on the contrary, the contents of more saturated molecular species of all lipid classes increased. Based on the data obtained, a scheme for the polar and neutral lipid synthesis in brown algae was proposed. In addition, the influence of infection with the brown filamentous endophyte Laminariocolax aecidioides (Ectocarpales) on U. pinnatifida lipidome was studied. It was found that infection has the most noticeable effect on the molecular species composition of triacylglycerides, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylhydroxyethylglycine of the host macrophyte. In infected samples of algae, changes in the composition of triacylglycerides were revealed both in areas with the presence of an endophyte and in adjacent intact tissues, which may indicate the occurrence of a secondary infection. Full article

Neurodegenerative diseases are incurable and debilitating conditions, characterized by progressive loss and degeneration of vulnerable neuronal populations. Currently, there are no effective therapies available for the treatment of most neurodegenerative disorders. A panel of extracts exhibiting interesting chemical profiles among a high number of bacterial strains isolated from East Mediterranean marine sediments and macroorganisms were evaluated for their activity on TrkB-expressing cells. Among them, the actinobacterial strain Streptomyces sp. BI0788, exhibiting neuroprotective activity in vitro, was selected and cultivated in large-scale. The chemical analysis of its organic extract resulted in the isolation of four new butanolides (1, 4–6), along with two previously reported butanolides (2 and 3) and eight previously reported butenolides (7–14). Compounds 2–4 and 7–14 were evaluated for their neuroprotective effects on TrkB-expressing NIH-3T3 cells. Among them, metabolites 3, 4, 7, 10, 11, 13 and 14 exhibited significant protective activity on the aforementioned cells through the activation of TrkB, the high-affinity receptor for the Brain-Derived Neurotrophic Factor (BDNF), which is well known to play a crucial role in neuronal cell survival and maintenance. Full article

Epilepsy is a chronic neurological disorder that is more prevalent in children, and recurrent unprovoked seizures can lead to cognitive impairment. Numerous studies have reported the benefits of docosahexaenoic acid (DHA) on neurodevelopment and cognitive ability, while comparatively less attention has been given to eicosapentaenoic acid (EPA). Additionally, little is known about the effects and mechanisms of DHA and EPA in relation to seizure-induced cognitive impairment in the young rodent model. Current research indicates that ferroptosis is involved in epilepsy and cognitive deficiency in children. Further investigation is warranted to determine whether EPA or DHA can mitigate seizure-induced cognitive deficits by inhibiting ferroptosis. Therefore, this study was conducted to compare the effects of DHA and EPA on seizure-induced cognitive deficiency and reveal the underlying mechanisms focused on ferroptosis in a pentylenetetrazol (PTZ)-kindling young mice model. Mice were fed a diet containing DHA-enriched ethyl esters or EPA-enriched ethyl esters for 21 days at the age of 3 weeks and treated with PTZ (35 mg/kg, i.p.) every other day 10 times. The findings indicated that both EPA and DHA exhibited ameliorative effects on seizure-induced cognitive impairment, with EPA demonstrating a superior efficacy. Further mechanism study revealed that supplementation of DHA and EPA significantly increased cerebral DHA and EPA levels, balanced neurotransmitters, and inhibited ferroptosis by modulating iron homeostasis and reducing lipid peroxide accumulation in the hippocampus through activating the Nrf2/Sirt3 signal pathway. Notably, EPA exhibited better an advantage in ameliorating iron dyshomeostasis compared to DHA, owing to its stronger upregulation of Sirt3. These results indicate that DHA and EPA can efficaciously alleviate seizure-induced cognitive deficiency by inhibiting ferroptosis in PTZ-kindled young mice. Full article

Skeletal constructs of diverse marine sponges remain to be a sustainable source of biocompatible porous biopolymer-based 3D scaffolds for tissue engineering and technology, especially structures isolated from cultivated demosponges, which belong to the Verongiida order, due to the renewability of their chitinous, fibre-containing architecture focused attention. These chitinous scaffolds have already shown excellent and promising results in biomimetics and tissue engineering with respect to their broad diversity of cells. However, the mechanical features of these constructs have been poorly studied before. For the first time, the elastic moduli characterising the chitinous samples have been determined. Moreover, nanoindentation of the selected bromotyrosine-containing as well as pigment-free chitinous scaffolds isolated from selected verongiids was used in the study for comparative purposes. It was shown that the removal of bromotyrosines from chitin scaffolds results in a reduced elastic modulus; however, their hardness was relatively unaffected. Full article

Diabetes mellitus is a metabolic disorder characterized by hyperglycemia due to impaired insulin secretion, insulin resistance, or both. Oxidative stress and chronic low-grade inflammation play crucial roles in the pathophysiology of diabetes mellitus. There has been a growing interest in applying natural products to improve metabolic derangements without the side effects of anti-diabetic drugs. Microalgae biomass or extract and their bioactive compounds have been applied as nutraceuticals or additives in food products and health supplements. Several studies have demonstrated the therapeutic effects of microalgae and their bioactive compounds in improving insulin sensitivity attributed to their antioxidant, anti-inflammatory, and pancreatic β-cell protective properties. However, a review summarizing the progression in this topic is lacking despite the increasing number of studies reporting their anti-diabetic potential. In this review, we gathered the findings from in vitro, in vivo, and human studies to discuss the effects of microalgae and their bioactive compounds on diabetes mellitus and the mechanisms involved. Additionally, we discuss the limitations and future perspectives of developing microalgae-based compounds as a health supplement for diabetes mellitus. In conclusion, microalgae-based supplementation has the potential to improve diabetes mellitus and be applied in more clinical studies in the future. Full article