Marine Drugs

35 pages, 11739 KiB

Open AccessArticle

Combining In Vitro, In Vivo, and Network Pharmacology Assays to Identify Targets and Molecular Mechanisms of Spirulina-Derived Biomolecules against Breast Cancer

by Soha Osama Hassanin, Amany Mohammed Mohmmed Hegab, Reham Hassan Mekky, Mohamed Adel Said, Mona G. Khalil, Alaaeldin Ahmed Hamza and Amr Amin

Mar. Drugs 2024, 22(7), 328; https://doi.org/10.3390/md22070328 - 22 Jul 2024

Cited by 2 | Viewed by 1328

Abstract

The current research employed an animal model of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary gland carcinogenesis. The estrogen receptor-positive human breast adenocarcinoma cell line (MCF-7) was used for in vitro analysis. This was combined with a network pharmacology-based approach to assess the anticancer properties of Spirulina [...] Read more.

The current research employed an animal model of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary gland carcinogenesis. The estrogen receptor-positive human breast adenocarcinoma cell line (MCF-7) was used for in vitro analysis. This was combined with a network pharmacology-based approach to assess the anticancer properties of Spirulina (SP) extract and understand its molecular mechanisms. The results showed that the administration of 1 g/kg of SP increased the antioxidant activity by raising levels of catalase (CAT) and superoxide dismutase (SOD), while decreasing the levels of malonaldehyde (MDA) and protein carbonyl. A histological examination revealed reduced tumor occurrence, decreased estrogen receptor expression, suppressed cell proliferation, and promoted apoptosis in SP protected animals. In addition, SP disrupted the G2/M phase of the MCF-7 cell cycle, inducing apoptosis and reactive oxygen species (ROS) accumulation. It also enhanced intrinsic apoptosis in MCF-7 cells by upregulating cytochrome c, Bax, caspase-8, caspase-9, and caspase-7 proteins, while downregulating Bcl-2 production. The main compounds identified in the LC-MS/MS study of SP were 7-hydroxycoumarin derivatives of cinnamic acid, hinokinin, valeric acid, and α-linolenic acid. These substances specifically targeted three important proteins: ERK1/2 MAPK, PI3K-protein kinase B (AKT), and the epidermal growth factor receptor (EGFR). Network analysis and molecular docking indicated a significant binding affinity between SP and these proteins. This was verified by Western blot analysis that revealed decreased protein levels of p-EGFR, p-ERK1/2, and p-AKT following SP administration. SP was finally reported to suppress MCF-7 cell growth and induce apoptosis by modulating the PI3K/AKT/EGFR and MAPK signaling pathways suggesting EGFR as a potential target of SP in breast cancer (BC) treatment. Full article

(This article belongs to the Special Issue Discovery of Marine-Derived Anticancer Agents)

► Show Figures

Graphical abstract

22 pages, 3208 KiB

Open AccessEditor’s ChoiceReview

Seaweeds as Source of Bioactive Pigments with Neuroprotective and/or Anti-Neurodegenerative Activities: Astaxanthin and Fucoxanthin

by Estela Guardado Yordi, Amaury Pérez Martínez, Matteo Radice, Laura Scalvenzi, Reinier Abreu-Naranjo, Eugenio Uriarte, Lourdes Santana and Maria Joao Matos

Mar. Drugs 2024, 22(7), 327; https://doi.org/10.3390/md22070327 - 22 Jul 2024

Viewed by 3881

Abstract

The marine kingdom is an important source of a huge variety of scaffolds inspiring the design of new drugs. The complex molecules found in the oceans present a great challenge to organic and medicinal chemists. However, the wide variety of biological activities they [...] Read more.

The marine kingdom is an important source of a huge variety of scaffolds inspiring the design of new drugs. The complex molecules found in the oceans present a great challenge to organic and medicinal chemists. However, the wide variety of biological activities they can display is worth the effort. In this article, we present an overview of different seaweeds as potential sources of bioactive pigments with activity against neurodegenerative diseases, especially due to their neuroprotective effects. Along with a broad introduction to seaweed as a source of bioactive pigments, this review is especially focused on astaxanthin and fucoxanthin as potential neuroprotective and/or anti-neurodegenerative agents. PubMed and SciFinder were used as the main sources to search and select the most relevant scientific articles within the field. Full article

(This article belongs to the Special Issue Synthetic Chemistry in Marine Drug Discovery: Challenges and Opportunities)

► Show Figures

Figure 1

17 pages, 10763 KiB

Open AccessArticle

Molecular Dynamics Simulation Reveal the Structure–Activity Relationships of Kainoid Synthases

by Zeyu Fan, Xinhao Li, Ruoyu Jiang, Jinqian Li, Fangyu Cao, Mingjuan Sun and Lianghua Wang

Mar. Drugs 2024, 22(7), 326; https://doi.org/10.3390/md22070326 - 22 Jul 2024

Viewed by 858

Abstract

Kainoid synthases are key enzymes in the biosynthesis of kainoids. Kainoids, as represented by DA and KA, are a class of naturally occurring non-protein amino acids with strong neurotransmitter activity in the mammalian central nervous system. Marine algae kainoid synthases include PnDabC from [...] Read more.

Kainoid synthases are key enzymes in the biosynthesis of kainoids. Kainoids, as represented by DA and KA, are a class of naturally occurring non-protein amino acids with strong neurotransmitter activity in the mammalian central nervous system. Marine algae kainoid synthases include PnDabC from diatoms, which synthesizes domoic acid (DA), and DsKabC and GfKabC from red algae, which synthesize kainic acid (KA). Elucidation of the catalytic mechanism of kainoid synthases is of great significance for the rational design of better biocatalysts to promote the industrial production of kainoids for use in new drugs. Through modeling, molecular docking, and molecular dynamics simulations, we investigated the conformational dynamics of kainoid synthases. We found that the kainoid synthase complexes showed different stability in the simulation, and the binding and catalytic processes showed significant conformational transformations of kainoid synthase. The residues involved in specific interactions with the substrate contributed to the binding energy throughout the simulation process. Binding energy, the relaxed active pocket, electrostatic potential energy of the active pocket, the number and rotation of aromatic residues interacting with substrates during catalysis, and the number and frequency of hydrogen bonds between the individual functional groups revealed the structure–activity relationships and affected the degree of promiscuity of kainoid synthases. Our research enriches the understanding of the conformational dynamics of kainoid synthases and has potential guiding significance for their rational design. Full article

(This article belongs to the Special Issue Biosynthesis, Metabolism, Pharmacology and Biological Receptors of Marine Algal Toxins)

► Show Figures

Figure 1

21 pages, 6595 KiB

Open AccessArticle

Proteomics Analysis of the Protective Effect of Polydeoxyribonucleotide Extracted from Sea Cucumber (Apostichopus japonicus) Sperm in a Hydrogen Peroxide-Induced RAW264.7 Cell Injury Model

by Zhiqiang Shu, Yizhi Ji, Fang Liu, Yuexin Jing, Chunna Jiao, Yue Li, Yunping Zhao, Gongming Wang and Jian Zhang

Mar. Drugs 2024, 22(7), 325; https://doi.org/10.3390/md22070325 - 21 Jul 2024

Viewed by 1162

Abstract

Sea cucumber viscera contain various naturally occurring active substances, but they are often underutilized during sea cucumber processing. Polydeoxyribonucleotide (PDRN) is an adenosine A_2A receptor agonist that activates the A_2A receptor to produce various biological effects. Currently, most studies on the [...] Read more.

Sea cucumber viscera contain various naturally occurring active substances, but they are often underutilized during sea cucumber processing. Polydeoxyribonucleotide (PDRN) is an adenosine A_2A receptor agonist that activates the A_2A receptor to produce various biological effects. Currently, most studies on the activity of PDRN have focused on its anti-inflammatory, anti-apoptotic, and tissue repair properties, yet relatively few studies have investigated its antioxidant activity. In this study, we reported for the first time that PDRN was extracted from the sperm of Apostichopus japonicus (AJS-PDRN), and we evaluated its antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS), and hydroxyl radical scavenging assays. An in vitro injury model was established using H₂O₂-induced oxidative damage in RAW264.7 cells, and we investigated the protective effect of AJS-PDRN on these cells. Additionally, we explored the potential mechanism by which AJS-PDRN protects RAW264.7 cells from damage using iTRAQ proteomics analysis. The results showed that AJS-PDRN possessed excellent antioxidant activity and could significantly scavenge DPPH, ABTS, and hydroxyl radicals. In vitro antioxidant assays demonstrated that AJS-PDRN was cytoprotective and significantly enhanced the antioxidant capacity of RAW264.7 cells. The results of GO enrichment and KEGG pathway analysis indicate that the protective effects of AJS-PDRN pretreatment on RAW264.7 cells are primarily achieved through the regulation of immune and inflammatory responses, modulation of the extracellular matrix and signal transduction pathways, promotion of membrane repair, and enhancement of cellular antioxidant capacity. The results of a protein–protein interaction (PPI) network analysis indicate that AJS-PDRN reduces cellular oxidative damage by upregulating the expression of intracellular selenoprotein family members. In summary, our findings reveal that AJS-PDRN mitigates H₂O₂-induced oxidative damage through multiple pathways, underscoring its significant potential in the prevention and treatment of diseases caused by oxidative stress. Full article

(This article belongs to the Special Issue Marine Anti-Inflammatory and Antioxidant Agents, 4th Edition)

► Show Figures

Figure 1

20 pages, 8211 KiB

Open AccessArticle

Aspergillusidone G Potentiates the Anti-Inflammatory Effects of Polaprezinc in LPS-Induced BV2 Microglia: A Bioinformatics and Experimental Study

by Fangfang Ban, Longjian Zhou, Zhiyou Yang, Yayue Liu and Yi Zhang

Mar. Drugs 2024, 22(7), 324; https://doi.org/10.3390/md22070324 - 19 Jul 2024

Viewed by 2662

Abstract

Neuroinflammation is one of the main mechanisms involved in the progression of neurodegenerative diseases (NDs), and microglial activation is the main feature of neuroinflammation. Polaprezinc (Pol), a chelator of L-carnosine and zinc, is widely used as a clinical drug for gastric ulcers. However, [...] Read more.

Neuroinflammation is one of the main mechanisms involved in the progression of neurodegenerative diseases (NDs), and microglial activation is the main feature of neuroinflammation. Polaprezinc (Pol), a chelator of L-carnosine and zinc, is widely used as a clinical drug for gastric ulcers. However, its potential effects on NDs remain unexplored. In LPS-induced BV-2 microglia, we found that Pol reduced the generation of NO and ROS and revealed inhibited expression of iNOS, COX-2, and inflammatory factors such as IL-6, TNF-α, and 1L-1β by Pol using qRT-PCR and Western blotting. These effects were found to be associated with the suppression of the NF-κB signaling pathway. Moreover, we evaluated the potential synergistic effects of aspergillusidone G (Asp G) when combined with Pol. Remarkably, co-treatment with low doses of Asp G enhanced the NO inhibition by Pol from approximately 30% to 80% in LPS-induced BV2 microglia, indicating a synergistic anti-inflammatory effect. A bioinformatics analysis suggested that the synergistic mechanism of Asp G and Pol might be attributed to several targets, including NFκB1, NRF2, ABL1, TLR4, and PPARα. These findings highlight the anti-neuroinflammatory properties of Pol and its enhanced efficacy when combined with Asp G, proposing a novel therapeutic strategy for managing neuroinflammation in NDs. Full article

(This article belongs to the Special Issue Marine Alkaloids: Sources, Discovery, Diversity, and Bioactivities)

► Show Figures

Graphical abstract

25 pages, 8776 KiB

Open AccessEditor’s ChoiceArticle

From Sea to Science: Coral Aquaculture for Sustainable Anticancer Drug Development

by Hung-Yu Lin, Tsen-Ni Tsai, Kai-Cheng Hsu, Yu-Ming Hsu, Lin-Chien Chiang, Mohamed El-Shazly, Ken-Ming Chang, Yu-Hsuan Lin, Shang-Yi Tu, Tony Eight Lin, Ying-Chi Du, Yi-Chang Liu and Mei-Chin Lu

Mar. Drugs 2024, 22(7), 323; https://doi.org/10.3390/md22070323 - 19 Jul 2024

Viewed by 3142

Abstract

Marine natural products offer immense potential for drug development, but the limited supply of marine organisms poses a significant challenge. Establishing aquaculture presents a sustainable solution for this challenge by facilitating the mass production of active ingredients while reducing our reliance on wild [...] Read more.

Marine natural products offer immense potential for drug development, but the limited supply of marine organisms poses a significant challenge. Establishing aquaculture presents a sustainable solution for this challenge by facilitating the mass production of active ingredients while reducing our reliance on wild populations and harm to local environments. To fully utilize aquaculture as a source of biologically active products, a cell-free system was established to target molecular components with protein-modulating activity, including topoisomerase II, HDAC, and tubulin polymerization, using extracts from aquaculture corals. Subsequent in vitro studies were performed, including MTT assays, flow cytometry, confocal microscopy, and Western blotting, along with in vivo xenograft models, to verify the efficacy of the active extracts and further elucidate their cytotoxic mechanisms. Regulatory proteins were clarified using NGS and gene modification techniques. Molecular docking and SwissADME assays were performed to evaluate the drug-likeness and pharmacokinetic and medicinal chemistry-related properties of the small molecules. The extract from Lobophytum crassum (LCE) demonstrated potent broad-spectrum activity, exhibiting significant inhibition of tubulin polymerization, and showed low IC₅₀ values against prostate cancer cells. Flow cytometry and Western blotting assays revealed that LCE induced apoptosis, as evidenced by the increased expression of apoptotic protein-cleaved caspase-3 and the populations of early and late apoptotic cells. In the xenograft tumor experiments, LCE significantly suppressed tumor growth and reduced the tumor volume (PC3: 43.9%; Du145: 49.2%) and weight (PC3: 48.8%; Du145: 7.8%). Additionally, LCE inhibited prostate cancer cell migration, and invasion upregulated the epithelial marker E-cadherin and suppressed EMT-related proteins. Furthermore, LCE effectively attenuated TGF-β-induced EMT in PC3 and Du145 cells. Bioactivity-guided fractionation and SwissADME validation confirmed that LCE’s main component, 13-acetoxysarcocrassolide (13-AC), holds greater potential for the development of anticancer drugs. Full article

(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents 3.0)

► Show Figures

Figure 1

19 pages, 4488 KiB

Open AccessArticle

Systematical Investigation on Anti-Fatigue Function and Underlying Mechanism of High Fischer Ratio Oligopeptides from Antarctic Krill on Exercise-Induced Fatigue in Mice

by Sha-Yi Mao, Shi-Kun Suo, Yu-Mei Wang, Chang-Feng Chi and Bin Wang

Mar. Drugs 2024, 22(7), 322; https://doi.org/10.3390/md22070322 - 19 Jul 2024

Cited by 3 | Viewed by 920

Abstract

High Fischer ratio oligopeptides (HFOs) have a variety of biological activities, but their mechanisms of action for anti-fatigue are less systematically studied at present. This study aimed to systematically evaluate the anti-fatigue efficacy of HFOs from Antarctic krill (HFOs-AK) and explore its mechanism [...] Read more.

High Fischer ratio oligopeptides (HFOs) have a variety of biological activities, but their mechanisms of action for anti-fatigue are less systematically studied at present. This study aimed to systematically evaluate the anti-fatigue efficacy of HFOs from Antarctic krill (HFOs-AK) and explore its mechanism of action through establishing the fatigue model of endurance swimming in mice. Therefore, according to the comparison with the endurance swimming model group, HFOs-AK were able to dose-dependently prolong the endurance swimming time, reduce the levels of the metabolites (lactic acid, blood urea nitrogen, and blood ammonia), increase the content of blood glucose, muscle glycogen, and liver glycogen, reduce lactate dehydrogenase and creatine kinase extravasation, and protect muscle tissue from damage in the endurance swimming mice. HFOs-AK were shown to enhance Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase activities and increase ATP content in muscle tissue. Meanwhile, HFOs-AK also showed significantly antioxidant ability by increasing the activities of superoxide dismutase and glutathione peroxidase in the liver and decreasing the level of malondialdehyde. Further studies showed that HFOs-AK could regulate the body’s energy metabolism and thus exert its anti-fatigue effects by activating the AMPK signaling pathway and up-regulating the expression of p-AMPK and PGC-α proteins. Therefore, HFOs-AK can be used as an auxiliary functional dietary molecules to exert its good anti-fatigue activity and be applied to anti-fatigue functional foods. Full article

(This article belongs to the Special Issue Marine Bioactive Peptides—Structure, Function, and Application 2.0)

► Show Figures

Figure 1

44 pages, 3898 KiB

Open AccessReview

Recent Discovery of Nitrogen Heterocycles from Marine-Derived Aspergillus Species

by Jueying Shi, Miao Yu, Weikang Chen, Shiji Chen, Yikang Qiu, Zhenyang Xu, Yi Wang, Guolei Huang and Caijuan Zheng

Mar. Drugs 2024, 22(7), 321; https://doi.org/10.3390/md22070321 - 18 Jul 2024

Viewed by 2869

Abstract

Nitrogen heterocycles have drawn considerable attention because of their structurally novel and significant biological activities. Marine-derived fungi, especially the Aspergillus species, possess unique metabolic pathways to produce secondary metabolites with novel structures and potent biological activities. This review prioritizes the structural diversity and [...] Read more.

Nitrogen heterocycles have drawn considerable attention because of their structurally novel and significant biological activities. Marine-derived fungi, especially the Aspergillus species, possess unique metabolic pathways to produce secondary metabolites with novel structures and potent biological activities. This review prioritizes the structural diversity and biological activities of nitrogen heterocycles that are produced by marine-derived Aspergillus species from January 2019 to January 2024, and their relevant biological activities. A total of 306 new nitrogen heterocycles, including seven major categories—indole alkaloids, diketopiperazine alkaloids, quinazoline alkaloids, isoquinoline alkaloids pyrrolidine alkaloids, cyclopeptide alkaloids, and other heterocyclic alkaloids—are presented in this review. Among these nitrogen heterocycles, 52 compounds had novel skeleton structures. Remarkably, 103 compounds showed various biological activities, such as cytotoxic, antimicrobial, anti-inflammatory, antifungal, anti-virus, and enzyme-inhibitory activities, and 21 compounds showed potent activities. This paper will guide further investigations into the structural diversity and biological activities of nitrogen heterocycles derived from the Aspergillus species and their potential contributions to the future development of new natural drug products in the medicinal and agricultural fields. Full article

(This article belongs to the Special Issue Pharmacological Potential of Marine Natural Products, 2nd Edition)

► Show Figures

Figure 1

17 pages, 1907 KiB

Open AccessArticle

Cell-Death Metabolites from Cocconeis scutellum var. parva Identified by Integrating Bioactivity-Based Fractionation and Non-Targeted Metabolomic Approaches

by Carlos Sanchez-Arcos, Mirko Mutalipassi, Valerio Zupo and Eric von Elert

Mar. Drugs 2024, 22(7), 320; https://doi.org/10.3390/md22070320 - 18 Jul 2024

Viewed by 978

Abstract

Epiphytic diatoms growing in Mediterranean seagrass meadows, particularly those of the genus Cocconeis, are abundant and ecologically significant, even in naturally acidified environments. One intriguing aspect of some benthic diatoms is their production of an unidentified cell-death-promoting compound, which induces destruction of [...] Read more.

Epiphytic diatoms growing in Mediterranean seagrass meadows, particularly those of the genus Cocconeis, are abundant and ecologically significant, even in naturally acidified environments. One intriguing aspect of some benthic diatoms is their production of an unidentified cell-death-promoting compound, which induces destruction of the androgenic gland in Hippolyte inermis Leach, 1816, a shrimp exhibiting protandric hermaphroditism, principally under normal environmental pH levels. The consumption of Cocconeis spp. by this shrimp is vital for maintaining the stability of its natural populations. Although many attempts have been made to reveal the identity of the apoptotic compound, it is still unknown. In this study, we strategically integrated a bioactivity-based fractionation, a metabolomic approach, and two different experimental avenues to identify potential apoptotic metabolites from Cocconeis scutellum var. parva responsible for the sex reversal in H. inermis. Our integrated analysis uncovered two potential candidate metabolites, one putatively identified as a lysophosphatidylglycerol (LPG) (16:1) and the other classified as a fatty acid ester. This is the first time LPG (16:1) has been reported in C. scutellum var. parva and associated with cell-death processes. These candidate metabolites mark substantial progress in elucidating the factors responsible for triggering the removal of the androgenic gland in the early post-larval phases of H. inermis. Full article

(This article belongs to the Special Issue Marine Algal Chemical Ecology 2024)

► Show Figures

Figure 1

15 pages, 1335 KiB

Open AccessArticle

Chemical and Antioxidant Properties of Solvent and Enzyme-Assisted Extracts of Fucus vesiculosus and Porphyra dioica

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

Mar. Drugs 2024, 22(7), 319; https://doi.org/10.3390/md22070319 - 18 Jul 2024

Viewed by 944

Abstract

Extraction strategies impact the efficiency and nature of extracted compounds. This work assessed the chemical composition and antioxidant capacity of ethanolic, hydroethanolic, and aqueous versus enzyme-assisted extracts (isolated or with the sequential use of alcalase^®, cellulase^®, and viscozyme^® [...] Read more.

Extraction strategies impact the efficiency and nature of extracted compounds. This work assessed the chemical composition and antioxidant capacity of ethanolic, hydroethanolic, and aqueous versus enzyme-assisted extracts (isolated or with the sequential use of alcalase^®, cellulase^®, and viscozyme^®) of the macroalgae Fucus vesiculosus (brown, Phaeophyceae) and Porphyra dioica (red, Rhodophyta. For both macroalgae, enzyme-assisted extraction (EAE) was the most efficient process compared to solvent-assisted extraction (SAE), independent of solvent. Fucus vesiculosus extraction yields were higher for EAE than for SAE (27.4% to 32.2% and 8.2% to 30.0%, respectively). Total phenolics content (TPC) was at least 10-fold higher in EAE extracts (229.2 to 311.3 GAE/g_extract) than in SAE (4.34 to 19.6 GAE/g_extract) counterparts and correlated well with antioxidant capacity (ABTS and ORAC methods), with EAE achieving values up to 8- and 2.6-fold higher than those achieved by SAE, respectively. Porphyra dioica followed F. vesiculosus’s trend for extraction yields (37.5% to 51.6% for EAE and 5.7% to 35.1% for SAE), TPC, although of a lower magnitude, (0.77 to 8.95 GAE/g_extract for SE and 9.37 to 14.73 GAE/g_extract for EAE), and antioxidant capacity. Aqueous extracts registered the highest DPPH values for both macroalgae, with 2.3 µmol TE/g_extract and 13.3 µmol TE/g_extract for F. vesiculosus and P. dioica, respectively. EAE was a more efficient process in the extraction of soluble protein and reducing sugars in comparison to SAE. Furthermore, an improved effect of enzyme-assisted combinations was observed for almost all analyzed parameters. This study shows the promising application of enzyme-assisted extraction for the extraction of valuable compounds from F. vesiculosus and P.dioica, making them excellent functional ingredients for a wide range of health and food industrial applications. Full article

(This article belongs to the Special Issue High-Value Algae Products)

► Show Figures

Figure 1

19 pages, 1553 KiB

Open AccessArticle

Chitosan-Based Oleogels: Emulsion Drying Kinetics and Physical, Rheological, and Textural Characteristics of Olive Oil Oleogels

by Mario Lama, Leticia Montes, Daniel Franco, Amaya Franco-Uría and Ramón Moreira

Mar. Drugs 2024, 22(7), 318; https://doi.org/10.3390/md22070318 - 17 Jul 2024

Viewed by 814

Abstract

Oleogels are of high interest as promising substitutes for trans fats in foods. An emulsion-templated method was used to trap olive oil in the chitosan crosslinked with vanillin matrix. Oil in water emulsions (50:50 w/w) with different chitosan content (0.7 [...] Read more.

Oleogels are of high interest as promising substitutes for trans fats in foods. An emulsion-templated method was used to trap olive oil in the chitosan crosslinked with vanillin matrix. Oil in water emulsions (50:50 w/w) with different chitosan content (0.7 and 0.8% w/w) with a constant vanillin/chitosan ratio (1.3) were air-dried at different temperatures (50, 60, 70, and 80 °C) and freeze-dried (−26 °C and 0.1 mbar) to produce oleogels. Only falling rate periods were determined during air-drying kinetics and were successfully modeled with empirical and diffusional models. At a drying temperature of 70 °C, the drying kinetics were the fastest. The viscoelasticity of oleogels showed that the elastic modulus significantly increased after drying at 60 and 70 °C, and those dried at 50 °C and freeze-dried were weaker. All oleogels showed high oil binding capacity (>91%), but the highest values (>97%) were obtained in oleogels with a threshold elastic modulus (50,000 Pa). The oleogels’ color depended on the drying temperature and chitosan content (independent of the drying method). Significant differences were observed between air-dried and freeze-dried oleogels with respect to oxidative stability. Oxidation increased with the air-drying time regardless of chitosan content. The found results indicated that drying conditions must be carefully selected to produce oleogels with specific features. Full article

(This article belongs to the Special Issue Marine Drugs Research in Spain 2nd Edition)

► Show Figures

Figure 1

25 pages, 5762 KiB

Open AccessArticle

New Zosteropenillines and Pallidopenillines from the Seagrass-Derived Fungus Penicillium yezoense KMM 4679

by Elena V. Leshchenko, Ekaterina A. Chingizova, Alexandr S. Antonov, Nadezhda P. Shlyk, Gleb V. Borkunov, Dmitrii V. Berdyshev, Viktoria E. Chausova, Natalya N. Kirichuk, Yuliya V. Khudyakova, Artur R. Chingizov, Anatoly I. Kalinovsky, Roman S. Popov, Natalya Yu. Kim, Ksenia A. Chadova, Ekaterina A. Yurchenko, Marina P. Isaeva and Anton N. Yurchenko

Mar. Drugs 2024, 22(7), 317; https://doi.org/10.3390/md22070317 - 17 Jul 2024

Viewed by 2706

Abstract

Ten new decalin polyketides, zosteropenilline M (1), 11-epi-8-hydroxyzosteropenilline M (2), zosteropenilline N (3), 8-hydroxyzosteropenilline G (4), zosteropenilline O (5), zosteropenilline P (6), zosteropenilline Q (7), 13-dehydroxypallidopenilline A [...] Read more.

Ten new decalin polyketides, zosteropenilline M (1), 11-epi-8-hydroxyzosteropenilline M (2), zosteropenilline N (3), 8-hydroxyzosteropenilline G (4), zosteropenilline O (5), zosteropenilline P (6), zosteropenilline Q (7), 13-dehydroxypallidopenilline A (8), zosteropenilline R (9) and zosteropenilline S (10), together with known zosteropenillines G (11) and J (12), pallidopenilline A (13) and 1-acetylpallidopenilline A (14), were isolated from the ethyl acetate extract of the fungus Penicillium yezoense KMM 4679 associated with the seagrass Zostera marina. The structures of isolated compounds were established based on spectroscopic methods. The absolute configurations of zosteropenilline Q (7) and zosteropenilline S (10) were determined using a combination of the modified Mosher’s method and ROESY data. The absolute configurations of zosteropenilline M (1) and zosteropenilline N (3) were determined using time-dependent density functional theory (TD-DFT) calculations of the ECD spectra. A biogenetic pathway for compounds 1–14 is proposed. The antimicrobial, cytotoxic and cytoprotective activities of the isolated compounds were also studied. The significant cytoprotective effects of the new zosteropenilline M and zosteropenillines O and R were found in a cobalt chloride (II) mimic in in vitro hypoxia in HEK-293 cells. 1-Acetylpallidopenilline A (14) exhibited high inhibition of human breast cancer MCF-7 cell colony formation with IC₅₀ of 0.66 µM and its anticancer effect was reduced when MCF-7 cells were pretreated with 4-hydroxitamoxifen. Thus, we propose 1-acetylpallidopenilline A as a new xenoestrogen with significant activity against breast cancer. Full article

(This article belongs to the Collection Marine Compounds and Cancer)

► Show Figures

Graphical abstract

27 pages, 14164 KiB

Open AccessArticle

A Comparative Analysis of the Anti-Tumor Activity of Sixteen Polysaccharide Fractions from Three Large Brown Seaweed, Sargassum horneri, Scytosiphon lomentaria, and Undaria pinnatifida

by Lin Song, Yunze Niu, Ran Chen, Hao Ju, Zijian Liu, Bida Zhang, Wancui Xie and Yi Gao

Mar. Drugs 2024, 22(7), 316; https://doi.org/10.3390/md22070316 - 16 Jul 2024

Viewed by 958

Abstract

Searching for natural products with anti-tumor activity is an important aspect of cancer research. Seaweed polysaccharides from brown seaweed have shown promising anti-tumor activity; however, their structure, composition, and biological activity vary considerably, depending on many factors. In this study, 16 polysaccharide fractions [...] Read more.

Searching for natural products with anti-tumor activity is an important aspect of cancer research. Seaweed polysaccharides from brown seaweed have shown promising anti-tumor activity; however, their structure, composition, and biological activity vary considerably, depending on many factors. In this study, 16 polysaccharide fractions were extracted and purified from three large brown seaweed species (Sargassum horneri, Scytosiphon lomentaria, and Undaria pinnatifida). The chemical composition analysis revealed that the polysaccharide fractions have varying molecular weights ranging from 8.889 to 729.67 kDa, and sulfate contents ranging from 0.50% to 10.77%. Additionally, they exhibit different monosaccharide compositions and secondary structures. Subsequently, their anti-tumor activity was compared against five tumor cell lines (A549, B16, HeLa, HepG_2, and SH-SY5Y). The results showed that different fractions exhibited distinct anti-tumor properties against tumor cells. Flow cytometry and cytoplasmic fluorescence staining (Hoechst/AO staining) further confirmed that these effective fractions significantly induce tumor cell apoptosis without cytotoxicity. qRT-RCR results demonstrated that the polysaccharide fractions up-regulated the expression of Caspase-3, Caspase-8, Caspase-9, and Bax while down-regulating the expression of Bcl-2 and CDK-2. This study comprehensively compared the anti-tumor activity of polysaccharide fractions from large brown seaweed, providing valuable insights into the potent combinations of brown seaweed polysaccharides as anti-tumor agents. Full article

(This article belongs to the Collection Marine Polysaccharides)

► Show Figures

Figure 1

14 pages, 8540 KiB

Open AccessArticle

Marizomib (Salinosporamide A) Promotes Apoptosis in A375 and G361 Melanoma Cancer Cells

by Wiktoria Monika Piskorz, Rafał Krętowski and Marzanna Cechowska-Pasko

Mar. Drugs 2024, 22(7), 315; https://doi.org/10.3390/md22070315 - 15 Jul 2024

Cited by 1 | Viewed by 946

Abstract

Malignant melanoma—a tumor originating from melanocytes—is characterized by dynamic growth and frequent metastases in the early stage of development. Current therapy methods are still insufficient, and there is a need to search for new ways of treating this malady. The induction of apoptosis—physiological [...] Read more.

Malignant melanoma—a tumor originating from melanocytes—is characterized by dynamic growth and frequent metastases in the early stage of development. Current therapy methods are still insufficient, and there is a need to search for new ways of treating this malady. The induction of apoptosis—physiological cell death—by proteasome inhibitors is recognized as an effective method of non-invasive elimination of cancer cells. In our research, we wanted to check the potential of marizomib (MZB, salinosporamide A, NPI-0052)—an irreversible proteasome inhibitor derived from the marine actinomycete Salinispora tropica—to induce apoptosis in A375 and G361 malignant melanoma cells. We determined the cytotoxic activity of marizomib by performing an MTT test. Ethidium bromide and acridine orange staining demonstrated the disruption of membrane integrity in the examined cell lines. We confirmed the proapoptotic activity of marizomib by flow cytometry with the use of an FITC-Annexin V assay. A Western blot analysis presented an increase in the expression of proteins related to endoplasmic reticulum (ER) stress as well as markers of the apoptosis. The gathered findings suggest that marizomib induced the ER stress in the examined melanoma cancer cells and directed them towards the apoptosis pathway. Full article

(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents 4.0)

► Show Figures

Figure 1

14 pages, 3175 KiB

Open AccessArticle

Stapling Cysteine[2,4] Disulfide Bond of α-Conotoxin LsIA and Its Potential in Target Delivery

by Xin Sun, Jiangnan Hu, Maomao Ren, Hong Chang, Dongting Zhangsun, Baojian Zhang and Shuai Dong

Mar. Drugs 2024, 22(7), 314; https://doi.org/10.3390/md22070314 - 14 Jul 2024

Viewed by 1117

Abstract

α-Conotoxins, as selective nAChR antagonists, can be valuable tools for targeted drug delivery and fluorescent labeling, while conotoxin-drug or conotoxin-fluorescent conjugates through the disulfide bond are rarely reported. Herein, we demonstrate the [2,4] disulfide bond of α-conotoxin as a feasible new chemical modification [...] Read more.

α-Conotoxins, as selective nAChR antagonists, can be valuable tools for targeted drug delivery and fluorescent labeling, while conotoxin-drug or conotoxin-fluorescent conjugates through the disulfide bond are rarely reported. Herein, we demonstrate the [2,4] disulfide bond of α-conotoxin as a feasible new chemical modification site. In this study, analogs of the α-conotoxin LsIA cysteine[2,4] were synthesized by stapling with five linkers, and their inhibitory activities against human α7 and rat α3β2 nAChRs were maintained. To further apply this method in targeted delivery, the alkynylbenzyl bromide linker was synthesized and conjugated with Coumarin 120 (AMC) and Camptothecin (CPT) by copper-catalyzed click chemistry, and then stapled between cysteine[2,4] of the LsIA to construct a fluorescent probe and two peptide-drug conjugates. The maximum emission wavelength of the LsIA fluorescent probe was 402.2 nm, which was essentially unchanged compared with AMC. The cytotoxic activity of the LsIA peptide-drug conjugates on human A549 was maintained in vitro. The results demonstrate that the stapling of cysteine[2,4] with alkynylbenzyl bromide is a simple and feasible strategy for the exploitation and utilization of the α-conotoxin LsIA. Full article

(This article belongs to the Section Marine Toxins)

► Show Figures

Graphical abstract

22 pages, 2518 KiB

Open AccessReview

Anti-Biofilm Extracts and Molecules from the Marine Environment

by Flore Caudal, Catherine Roullier, Sophie Rodrigues, Alain Dufour, Sébastien Artigaud, Gwenaelle Le Blay, Alexis Bazire and Sylvain Petek

Mar. Drugs 2024, 22(7), 313; https://doi.org/10.3390/md22070313 - 10 Jul 2024

Cited by 1 | Viewed by 4313

Abstract

Pathogenic bacteria and their biofilms are involved in many diseases and represent a major public health problem, including the development of antibiotic resistance. These biofilms are known to cause chronic infections for which conventional antibiotic treatments are often ineffective. The search for new [...] Read more.

Pathogenic bacteria and their biofilms are involved in many diseases and represent a major public health problem, including the development of antibiotic resistance. These biofilms are known to cause chronic infections for which conventional antibiotic treatments are often ineffective. The search for new molecules and innovative solutions to combat these pathogens and their biofilms has therefore become an urgent need. The use of molecules with anti-biofilm activity would be a potential solution to these problems. The marine world is rich in micro- and macro-organisms capable of producing secondary metabolites with original skeletons. An interest in the chemical strategies used by some of these organisms to regulate and/or protect themselves against pathogenic bacteria and their biofilms could lead to the development of bioinspired, eco-responsible solutions. Through this original review, we listed and sorted the various molecules and extracts from marine organisms that have been described in the literature as having strictly anti-biofilm activity, without bactericidal activity. Full article

(This article belongs to the Special Issue Marine Anti-Biofilm Compounds from Natural to Synthetic Compounds)

► Show Figures

Graphical abstract

19 pages, 2859 KiB

Open AccessArticle

Australian Marine and Terrestrial Streptomyces-Derived Surugamides, and Synthetic Analogs, and Their Ability to Inhibit Dirofilaria immitis (Heartworm) Motility

by Taizong Wu, Waleed M. Hussein, Kaumadi Samarasekera, Yuxuan Zhu, Zeinab G. Khalil, Shengbin Jin, David F. Bruhn, Yovany Moreno, Angela A. Salim and Robert J. Capon

Mar. Drugs 2024, 22(7), 312; https://doi.org/10.3390/md22070312 - 9 Jul 2024

Cited by 3 | Viewed by 5372

Abstract

A bioassay-guided chemical investigation of a bacterium, Streptomyces sp. CMB-MRB032, isolated from sheep feces collected near Bathurst, Victoria, Australia, yielded the known polyketide antimycins A4a (1) and A2a (2) as potent inhibitors of Dirofilaria immitis (heartworm) microfilaria (mf) motility [...] Read more.

A bioassay-guided chemical investigation of a bacterium, Streptomyces sp. CMB-MRB032, isolated from sheep feces collected near Bathurst, Victoria, Australia, yielded the known polyketide antimycins A4a (1) and A2a (2) as potent inhibitors of Dirofilaria immitis (heartworm) microfilaria (mf) motility (EC₅₀ 0.0013–0.0021 µg/mL), along with the octapeptide surugamide A (3) and the new N-methylated analog surugamide K (4). With biological data suggesting surugamides may also exhibit activity against D. immitis, a GNPS molecular network analysis of a library of microbes sourced from geographically diverse Australian ecosystems identified a further five taxonomically and chemically distinct surugamide producers. Scaled-up cultivation of one such producer, Streptomyces sp. CMB-M0112 isolated from a marine sediment collected at Shorncliff, Qld, Australia, yielded 3 along with the new acyl-surugamides A1–A4 (5–8). Solid-phase peptide synthesis provided additional synthetic analogs, surugamides S1–S3 (9–11), while derivatization of 3 returned the semi-synthetic surugamide S4 (12) and acyl-surugamides AS1–AS3 (13–15). The natural acyl-surugamide A3 (7) and semi-synthetic acyl-surugamide AS3 (15) were shown to selectively inhibit D. immitis mf motility (EC₅₀ 3.3–3.4 µg/mL), however, unlike antimycins 1 and 2, were inactive against the gastrointestinal nematode Haemonchus contortus L1–L3 larvae (EC₅₀ > 25 µg/mL) and were not cytotoxic to mammalian cells (human colorectal carcinoma SW620, IC₅₀ > 30 µg/mL). A structure–activity relationship (SAR) study on the surugamides 3–15 revealed that selective acylation of the Lys³-ε-NH₂ correlates with anthelmintic activity. Full article

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

► Show Figures

Graphical abstract

19 pages, 5252 KiB

Open AccessArticle

Toxin Dynamics among Populations of the Bioluminescent HAB Species Pyrodinium bahamense from the Indian River Lagoon, FL

by Kathleen D. Cusick, Bofan Wei, Sydney Hall, Nicole Brown, Edith A. Widder and Gregory L. Boyer

Mar. Drugs 2024, 22(7), 311; https://doi.org/10.3390/md22070311 - 4 Jul 2024

Viewed by 1133

Abstract

Dinoflagellate species that form some of the most frequent toxic blooms are also bioluminescent, yet the two traits are rarely linked when studying bloom development and persistence. P. bahamense is a toxic, bioluminescent dinoflagellate that previously bloomed in Florida with no known record [...] Read more.

Dinoflagellate species that form some of the most frequent toxic blooms are also bioluminescent, yet the two traits are rarely linked when studying bloom development and persistence. P. bahamense is a toxic, bioluminescent dinoflagellate that previously bloomed in Florida with no known record of saxitoxin (STX) production. Over the past 20 years, STX was identified in P. bahamense populations. The goal of this study was to examine toxin dynamics and associated molecular mechanisms in spatially and temporally distinct P. bahamense populations from the Indian River Lagoon, FL. SxtA4 is a key gene required for toxin biosynthesis. SxtA4 genotype analysis was performed on individual cells from multiple sites. Cell abundance, toxin quota cell⁻¹, and sxtA4 and RubisCo (rbcL) transcript abundance were also measured. There was a significant negative correlation between cell abundance and toxin quota cell⁻¹. While the sxtA4+ genotype was dominant at all sites, its frequency varied, but it occurred at 90–100% in many samples. The underlying mechanism for toxin decrease with increased cell abundance remains unknown. However, a strong, statistically significant negative correlation was found between stxA4 transcripts and the sxtA4/rbcL ratio, suggesting cells make fewer sxtA4 transcripts as a bloom progresses. However, the influence of sxtA4− cells must also be considered. Future plans include bioluminescence measurements, normalized to a per cell basis, at sites when toxicity is measured along with concomitant quantification of sxtA4 gene and transcript copy numbers as a means to elucidate whether changes in bloom toxicity are driven more at the genetic (emergence of sxtA4− cells) or transcriptional (repression of sxtA4 in sxtA4+ cells) level. Based on the results of this study, a model is proposed that links the combined traits of toxicity and bioluminescence in P. bahamense bloom development. Full article

(This article belongs to the Special Issue Biosynthesis, Metabolism, Pharmacology and Biological Receptors of Marine Algal Toxins)

► Show Figures

Figure 1

13 pages, 1730 KiB

Open AccessArticle

Total Synthesis and Biological Profiling of Putative (±)-Marinoaziridine B and (±)-N-Methyl Marinoaziridine A

by Anđela Buljan, Višnja Stepanić, Ana Čikoš, Sanja Babić Brčić, Krunoslav Bojanić and Marin Roje

Mar. Drugs 2024, 22(7), 310; https://doi.org/10.3390/md22070310 - 3 Jul 2024

Viewed by 1318

Abstract

The total synthesis of two new marine natural products, (±)-marinoaziridine B 7 and (±)-N-methyl marinoaziridine A 8, was accomplished. The (±)-marinoaziridine 7 was prepared in a six-step linear sequence with a 2% overall yield. The key steps in our strategy [...] Read more.

The total synthesis of two new marine natural products, (±)-marinoaziridine B 7 and (±)-N-methyl marinoaziridine A 8, was accomplished. The (±)-marinoaziridine 7 was prepared in a six-step linear sequence with a 2% overall yield. The key steps in our strategy were the preparation of the chiral epoxide (±)-5 using the Johnson Corey Chaykovsky reaction, followed by the ring-opening reaction and the Staudinger reaction. The N,N-dimethylation of compound (±)-7 gives (±)-N-methyl marinoaziridine A 8. The NMR spectra of synthetized (±)-marinoaziridine B 7 and isolated natural product did not match. The compounds are biologically characterized using relevant in silico, in vitro and in vivo methods. In silico ADMET and bioactivity profiling predicted toxic and neuromodulatory effects. In vitro screening by MTT assay on three cell lines (MCF-7, H-460, HEK293T) showed that both compounds exhibited moderate to strong antiproliferative and cytotoxic effects. Antimicrobial tests on bacterial cultures of Escherichia coli and Staphylococcus aureus demonstrated the dose-dependent inhibition of the growth of both bacteria. In vivo toxicological tests were performed on zebrafish Danio rerio and showed a significant reduction of zebrafish mortality due to N-methylation in (±)-8. Full article

(This article belongs to the Special Issue Total Synthesis and Synthetic Approaches towards Marine Bioactive Natural Products and Analogues)

► Show Figures

Figure 1

58 pages, 5548 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Marine Pharmacology in 2019–2021: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action

by Alejandro M. S. Mayer, Veronica A. Mayer, Michelle Swanson-Mungerson, Marsha L. Pierce, Abimael D. Rodríguez, Fumiaki Nakamura and Orazio Taglialatela-Scafati

Mar. Drugs 2024, 22(7), 309; https://doi.org/10.3390/md22070309 - 30 Jun 2024

Cited by 1 | Viewed by 2204

Abstract

The current 2019–2021 marine pharmacology literature review provides a continuation of previous reviews covering the period 1998 to 2018. Preclinical marine pharmacology research during 2019–2021 was published by researchers in 42 countries and contributed novel mechanism-of-action pharmacology for 171 structurally characterized marine compounds. [...] Read more.

The current 2019–2021 marine pharmacology literature review provides a continuation of previous reviews covering the period 1998 to 2018. Preclinical marine pharmacology research during 2019–2021 was published by researchers in 42 countries and contributed novel mechanism-of-action pharmacology for 171 structurally characterized marine compounds. The peer-reviewed marine natural product pharmacology literature reported antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral mechanism-of-action studies for 49 compounds, 87 compounds with antidiabetic and anti-inflammatory activities that also affected the immune and nervous system, while another group of 51 compounds demonstrated novel miscellaneous mechanisms of action, which upon further investigation, may contribute to several pharmacological classes. Thus, in 2019–2021, a very active preclinical marine natural product pharmacology pipeline provided novel mechanisms of action as well as new lead chemistry for the clinical marine pharmaceutical pipeline targeting the therapy of several disease categories. Full article

(This article belongs to the Section Marine Pharmacology)

► Show Figures

Figure 1

16 pages, 4540 KiB

Open AccessArticle

Protective Effects of Laminaria japonica Polysaccharide Composite Microcapsules on the Survival of Lactobacillus plantarum during Simulated Gastrointestinal Digestion and Heat Treatment

by Honghui Guo, Yelin Zhou, Quanling Xie, Hui Chen, Ming’en Zhang, Lei Yu, Guangyu Yan, Yan Chen, Xueliang Lin, Yiping Zhang and Zhuan Hong

Mar. Drugs 2024, 22(7), 308; https://doi.org/10.3390/md22070308 - 30 Jun 2024

Viewed by 1220

Abstract

To improve probiotics’ survivability during gastrointestinal digestion and heat treatment, Lactobacillus plantarum was microencapsulated by spray-drying using Laminaria japonica polysaccharide/sodium caseinate/gelatin (LJP/SC/GE) composites. Thermogravimetry and differential scanning calorimetry results revealed that the denaturation of LJP/SC/GE microcapsules requires higher thermal energy than that of [...] Read more.

To improve probiotics’ survivability during gastrointestinal digestion and heat treatment, Lactobacillus plantarum was microencapsulated by spray-drying using Laminaria japonica polysaccharide/sodium caseinate/gelatin (LJP/SC/GE) composites. Thermogravimetry and differential scanning calorimetry results revealed that the denaturation of LJP/SC/GE microcapsules requires higher thermal energy than that of SC/GE microcapsules, and the addition of LJP may improve thermal stability. Zeta potential measurements indicated that, at low pH of the gastric fluid, the negatively charged LJP attracted the positively charged SC/GE, helping to maintain an intact microstructure without disintegration. The encapsulation efficiency of L. plantarum-loaded LJP/SC/GE microcapsules reached about 93.4%, and the survival rate was 46.9% in simulated gastric fluid (SGF) for 2 h and 96.0% in simulated intestinal fluid (SIF) for 2 h. In vitro release experiments showed that the LJP/SC/GE microcapsules could protect the viability of L. plantarum in SGF and release probiotics slowly in SIF. The cell survival of LJP/SC/GE microcapsules was significantly improved during the heat treatment compared to SC/GE microcapsules and free cells. LJP/SC/GE microcapsules can increase the survival of L. plantarum by maintaining the lactate dehydrogenase and Na⁺-K⁺-ATPase activity. Overall, this study demonstrates the great potential of LJP/SC/GE microcapsules to protect and deliver probiotics in food and pharmaceutical systems. Full article

(This article belongs to the Special Issue Marine Biopolymers and Their Applications in Drug Delivery)

► Show Figures

Figure 1

12 pages, 2231 KiB

Open AccessArticle

ROS Induced by Aphrocallistes vastus Lectin Enhance Oncolytic Vaccinia Virus Replication and Induce Apoptosis in Hepatocellular Carcinoma Cells

by Yanan Zhang, Ying Zhu, Gaohui Jiang, Ke Chen, Guohui Zhang, Kan Chen, Ting Ye, Yanrong Zhou and Gongchu Li

Mar. Drugs 2024, 22(7), 307; https://doi.org/10.3390/md22070307 - 30 Jun 2024

Cited by 1 | Viewed by 1267

Abstract

Oncolytic virotherapy is expected to provide a new treatment strategy for cancer. Aphrocallistes vastus lectin (AVL) is a Ca²⁺-dependent lectin receptor containing the conserved domain of C-type lectin and the hydrophobic N-terminal region, which can bind to the bird’s nest glycoprotein [...] Read more.

Oncolytic virotherapy is expected to provide a new treatment strategy for cancer. Aphrocallistes vastus lectin (AVL) is a Ca²⁺-dependent lectin receptor containing the conserved domain of C-type lectin and the hydrophobic N-terminal region, which can bind to the bird’s nest glycoprotein and D-galactose. Our previous studies suggested that the oncolytic vaccinia virus (oncoVV) armed with the AVL gene exerted remarkable replication and antitumor effects in vitro and in vivo. In this study, we found that oncoVV-AVL may reprogram the metabolism of hepatocellular carcinoma cells to promote ROS, and elevated ROS subsequently promoted viral replication and induced apoptosis. This study will provide a new theoretical basis for the application of oncoVV-AVL in liver cancer. Full article

(This article belongs to the Special Issue Marine Lectins 2nd Edition)

► Show Figures

Figure 1

13 pages, 3126 KiB

Open AccessArticle

Light Intensity Enhances the Lutein Production in Chromochloris zofingiensis Mutant LUT-4

by Qiaohong Chen, Mingmeng Liu, Wujuan Mi, Dong Wan, Gaofei Song, Weichao Huang and Yonghong Bi

Mar. Drugs 2024, 22(7), 306; https://doi.org/10.3390/md22070306 - 29 Jun 2024

Viewed by 999

Abstract

Chromochloris zofingiensis, a unicellular green alga, is a potential source of natural carotenoids. In this study, the mutant LUT-4 was acquired from the chemical mutagenesis pool of C. zofingiensis strain. The biomass yield and lutein content of LUT-4 reached 9.23 g·L⁻¹ [...] Read more.

Chromochloris zofingiensis, a unicellular green alga, is a potential source of natural carotenoids. In this study, the mutant LUT-4 was acquired from the chemical mutagenesis pool of C. zofingiensis strain. The biomass yield and lutein content of LUT-4 reached 9.23 g·L⁻¹, and 0.209% of dry weight (DW) on Day 3, which was 49.4%, and 33% higher than that of wild-type (WT), respectively. The biomass yields of LUT-4 under 100, 300, and 500 µmol/m²/s reached 8.4 g·L⁻¹, 7.75 g·L⁻¹, and 6.6 g·L⁻¹, which was 10.4%, 21%, and 29.6% lower compared with the control, respectively. Under mixotrophic conditions, the lutein yields were significantly higher than that obtained in the control. The light intensity of 300 µmol/m²/s was optimal for lutein biosynthesis and the content of lutein reached 0.294% of DW on Day 3, which was 40.7% more than that of the control. When LUT-4 was grown under 300 µmol/m²/s, a significant increase in expression of genes implicated in lutein biosynthesis, including phytoene synthase (PSY), phytoene desaturase (PDS), and lycopene epsilon cyclase (LCYe) was observed. The changes in biochemical composition, Ace-CoA, pyruvate, isopentenyl pyrophosphate (IPP), and geranylgeranyl diphosphate (GGPP) contents during lutein biosynthesis were caused by utilization of organic carbon. It was thereby concluded that 300 µmol/m²/s was the optimal culture light intensity for the mutant LUT-4 to synthesize lutein. The results would be helpful for the large-scale production of lutein. Full article

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

► Show Figures

Graphical abstract

18 pages, 2645 KiB

Open AccessArticle

Potential of Marine Bacterial Metalloprotease A69 in the Preparation of Peanut Peptides with Angiotensin-Converting Enzyme (ACE)-Inhibitory and Antioxidant Properties

by Wen-Jie Cao, Rui Liu, Wen-Xiao Zhao, Jian Li, Yan Wang, Xiao-Jie Yuan, Hui-Lin Wang, Yu-Zhong Zhang, Xiu-Lan Chen and Yu-Qiang Zhang

Mar. Drugs 2024, 22(7), 305; https://doi.org/10.3390/md22070305 - 29 Jun 2024

Viewed by 1096

Abstract

Marine bacterial proteases have rarely been used to produce bioactive peptides, although many have been reported. This study aims to evaluate the potential of the marine bacterial metalloprotease A69 from recombinant Bacillus subtilis in the preparation of peanut peptides (PPs) with antioxidant activity [...] Read more.

Marine bacterial proteases have rarely been used to produce bioactive peptides, although many have been reported. This study aims to evaluate the potential of the marine bacterial metalloprotease A69 from recombinant Bacillus subtilis in the preparation of peanut peptides (PPs) with antioxidant activity and angiotensin-converting enzyme (ACE)-inhibitory activity. Based on the optimization of the hydrolysis parameters of protease A69, a process for PPs preparation was set up in which the peanut protein was hydrolyzed by A69 at 3000 U g⁻¹ and 60 °C, pH 7.0 for 4 h. The prepared PPs exhibited a high content of peptides with molecular weights lower than 1000 Da (>80%) and 3000 Da (>95%) and contained 17 kinds of amino acids. Moreover, the PPs displayed elevated scavenging of hydroxyl radical and 1,1-diphenyl-2-picryl-hydrazyl radical, with IC₅₀ values of 1.50 mg mL⁻¹ and 1.66 mg mL⁻¹, respectively, indicating the good antioxidant activity of the PPs. The PPs also showed remarkable ACE-inhibitory activity, with an IC₅₀ value of 0.71 mg mL⁻¹. By liquid chromatography mass spectrometry analysis, the sequences of 19 ACE inhibitory peptides and 15 antioxidant peptides were identified from the PPs. These results indicate that the prepared PPs have a good nutritional value, as well as good antioxidant and antihypertensive effects, and that the marine bacterial metalloprotease A69 has promising potential in relation to the preparation of bioactive peptides from peanut protein. Full article

(This article belongs to the Special Issue Biotechnological Applications of Marine Enzymes)

► Show Figures

Figure 1

33 pages, 3944 KiB

Open AccessReview

Immunomodulatory Compounds from the Sea: From the Origins to a Modern Marine Pharmacopoeia

by Edoardo Andrea Cutolo, Rosanna Campitiello, Roberto Caferri, Vittorio Flavio Pagliuca, Jian Li, Spiros Nicolas Agathos and Maurizio Cutolo

Mar. Drugs 2024, 22(7), 304; https://doi.org/10.3390/md22070304 - 28 Jun 2024

Cited by 1 | Viewed by 2030

Abstract

From sea shores to the abysses of the deep ocean, marine ecosystems have provided humanity with valuable medicinal resources. The use of marine organisms is discussed in ancient pharmacopoeias of different times and geographic regions and is still deeply rooted in traditional medicine. [...] Read more.

From sea shores to the abysses of the deep ocean, marine ecosystems have provided humanity with valuable medicinal resources. The use of marine organisms is discussed in ancient pharmacopoeias of different times and geographic regions and is still deeply rooted in traditional medicine. Thanks to present-day, large-scale bioprospecting and rigorous screening for bioactive metabolites, the ocean is coming back as an untapped resource of natural compounds with therapeutic potential. This renewed interest in marine drugs is propelled by a burgeoning research field investigating the molecular mechanisms by which newly identified compounds intervene in the pathophysiology of human diseases. Of great clinical relevance are molecules endowed with anti-inflammatory and immunomodulatory properties with emerging applications in the management of chronic inflammatory disorders, autoimmune diseases, and cancer. Here, we review the historical development of marine pharmacology in the Eastern and Western worlds and describe the status of marine drug discovery. Finally, we discuss the importance of conducting sustainable exploitation of marine resources through biotechnology. Full article

(This article belongs to the Special Issue Marine Immunomodulatory Compounds)

► Show Figures

Figure 1

16 pages, 1224 KiB

Open AccessEditor’s ChoiceArticle

Isolation and Total Synthesis of PM170453, a New Cyclic Depsipeptide Isolated from Lyngbya sp.

by Rogelio Fernández, Marta Pérez, Alejandro Losada, Silvia Reboredo, Asier Gómez-San Juan, María Jesús Martín, Andrés Francesch, Simon Munt and Carmen Cuevas

Mar. Drugs 2024, 22(7), 303; https://doi.org/10.3390/md22070303 - 28 Jun 2024

Viewed by 1435

Abstract

In our continuing search for biologically active new chemical entities from marine organisms, we have isolated a new cyclic depsipeptide, PM170453 (1), from a cyanobacterium of the genus Lyngbya sp., collected in the Indo-Pacific Ocean. Structure elucidation of the isolated compound [...] Read more.

In our continuing search for biologically active new chemical entities from marine organisms, we have isolated a new cyclic depsipeptide, PM170453 (1), from a cyanobacterium of the genus Lyngbya sp., collected in the Indo-Pacific Ocean. Structure elucidation of the isolated compound was determined by spectroscopic methods including MS, ¹H, ¹³C and 2D-NMR. To solve the supply problem for 1 and progress pharmaceutical development, the total synthesis of 1 that involves a total of 20 chemical steps in a convergent process was carried out. Its in vitro cytotoxic activity against four human tumor cell lines, as well as the inhibition of the interaction between the programmed cell death protein 1 PD-1 and its ligand PD-L1 were also evaluated. Full article

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

► Show Figures

Figure 1

18 pages, 10761 KiB

Open AccessArticle

Streptomyces-Fungus Co-Culture Enhances the Production of Borrelidin and Analogs: A Genomic and Metabolomic Approach

by Tan Liu, Xi Gui, Gang Zhang, Lianzhong Luo and Jing Zhao

Mar. Drugs 2024, 22(7), 302; https://doi.org/10.3390/md22070302 - 28 Jun 2024

Viewed by 1354

Abstract

The marine Streptomyces harbor numerous biosynthetic gene clusters (BGCs) with exploitable potential. However, many secondary metabolites cannot be produced under laboratory conditions. Co-culture strategies of marine microorganisms have yielded novel natural products with diverse biological activities. In this study, we explored the metabolic [...] Read more.

The marine Streptomyces harbor numerous biosynthetic gene clusters (BGCs) with exploitable potential. However, many secondary metabolites cannot be produced under laboratory conditions. Co-culture strategies of marine microorganisms have yielded novel natural products with diverse biological activities. In this study, we explored the metabolic profiles of co-cultures involving Streptomyces sp. 2-85 and Cladosporium sp. 3-22—derived from marine sponges. Combining Global Natural Products Social (GNPS) Molecular Networking analysis with natural product database mining, 35 potential antimicrobial metabolites annotated were detected, 19 of which were exclusive to the co-culture, with a significant increase in production. Notably, the Streptomyces-Fungus interaction led to the increased production of borrelidin and the discovery of several analogs via molecular networking. In this study, borrelidin was first applied to combat Saprolegnia parasitica, which caused saprolegniosis in aquaculture. We noted its superior inhibitory effects on mycelial growth with an EC₅₀ of 0.004 mg/mL and on spore germination with an EC₅₀ of 0.005 mg/mL compared to the commercial fungicide, preliminarily identifying threonyl-tRNA synthetase as its target. Further analysis of the associated gene clusters revealed an incomplete synthesis pathway with missing malonyl-CoA units for condensation within this strain, hinting at the presence of potential compensatory pathways. In conclusion, our findings shed light on the metabolic changes of marine Streptomyces and fungi in co-culture, propose the potential of borrelidin in the control of aquatic diseases, and present new prospects for antifungal applications. Full article

(This article belongs to the Special Issue Genome Mining and Drug Discovery of Marine and Halophilic Microorganisms)

► Show Figures

Graphical abstract

17 pages, 988 KiB

Open AccessReview

Marine-Derived Lipases for Enhancing Enrichment of Very-Long-Chain Polyunsaturated Fatty Acids with Reference to Omega-3 Fatty Acids

by Mahejbin Karia, Mona Kaspal, Mariam Alhattab and Munish Puri

Mar. Drugs 2024, 22(7), 301; https://doi.org/10.3390/md22070301 - 28 Jun 2024

Viewed by 3362

Abstract

Omega-3 fatty acids are essential fatty acids that are not synthesised by the human body and have been linked with the prevention of chronic illnesses such as cardiovascular and neurodegenerative diseases. However, the current dietary habits of the majority of the population include [...] Read more.

Omega-3 fatty acids are essential fatty acids that are not synthesised by the human body and have been linked with the prevention of chronic illnesses such as cardiovascular and neurodegenerative diseases. However, the current dietary habits of the majority of the population include lower omega-3 content compared to omega-6, which does not promote good health. To overcome this, pharmaceutical and nutraceutical companies aim to produce omega-3-fortified foods. For this purpose, various approaches have been employed to obtain omega-3 concentrates from sources such as fish and algal oil with higher amounts of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Among these techniques, enzymatic enrichment using lipase enzymes has gained tremendous interest as it is low in capital cost and simple in operation. Microorganism-derived lipases are preferred as they are easily produced due to their higher growth rate, and they hold the ability to be manipulated using genetic modification. This review aims to highlight the recent studies that have been carried out using marine lipases for the enrichment of omega-3, to provide insight into future directions. Overall, the covalent bond-based lipase immobilization to various support materials appears most promising; however, greener and less expensive options need to be strengthened. Full article

(This article belongs to the Special Issue Biotechnological Applications of Marine Enzymes)

► Show Figures

Figure 1

16 pages, 3682 KiB

Open AccessArticle

Posidonia oceanica (L.) Delile Is a Promising Marine Source Able to Alleviate Imiquimod-Induced Psoriatic Skin Inflammation

by Laura Micheli, Marzia Vasarri, Donatella Degl’Innocenti, Lorenzo Di Cesare Mannelli, Carla Ghelardini, Antiga Emiliano, Alice Verdelli, Marzia Caproni and Emanuela Barletta

Mar. Drugs 2024, 22(7), 300; https://doi.org/10.3390/md22070300 - 28 Jun 2024

Viewed by 1248

Abstract

Psoriasis is a chronic immune-mediated inflammatory cutaneous disease characterized by elevated levels of inflammatory cytokines and adipokine Lipocalin-2 (LCN-2). Recently, natural plant-based products have been studied as new antipsoriatic compounds. We investigate the ability of a leaf extract of the marine plant Posidonia [...] Read more.

Psoriasis is a chronic immune-mediated inflammatory cutaneous disease characterized by elevated levels of inflammatory cytokines and adipokine Lipocalin-2 (LCN-2). Recently, natural plant-based products have been studied as new antipsoriatic compounds. We investigate the ability of a leaf extract of the marine plant Posidonia oceanica (POE) to inhibit psoriatic dermatitis in C57BL/6 mice treated with Imiquimod (IMQ). One group of mice was topically treated with IMQ (IMQ mice) for 5 days, and a second group received POE orally before each topical IMQ treatment (IMQ-POE mice). Psoriasis Area Severity Index (PASI) score, thickness, and temperature of the skin area treated with IMQ were measured in both groups. Upon sacrifice, the organs were weighed, and skin biopsies and blood samples were collected. Plasma and lesional skin protein expression of IL-17, IL-23, IFN-γ, IL-2, and TNF-α and plasma LCN-2 concentration were evaluated by ELISA. PASI score, thickness, and temperature of lesional skin were reduced in IMQ-POE mice, as were histological features of psoriatic dermatitis and expression of inflammatory cytokines and LCN-2 levels. This preliminary study aims to propose P. oceanica as a promising naturopathic anti-inflammatory treatment that could be introduced in Complementary Medicine for psoriasis. Full article

(This article belongs to the Special Issue Marine Anti-inflammatory and Antioxidant Agents 3.0)

► Show Figures

Figure 1

29 pages, 1672 KiB

Open AccessReview

Whole-Cell Biosensor for Iron Monitoring as a Potential Tool for Safeguarding Biodiversity in Polar Marine Environments

by Marzia Calvanese, Caterina D’Angelo, Maria Luisa Tutino and Concetta Lauro

Mar. Drugs 2024, 22(7), 299; https://doi.org/10.3390/md22070299 - 28 Jun 2024

Viewed by 3123

Abstract

Iron is a key micronutrient essential for various essential biological processes. As a consequence, alteration in iron concentration in seawater can deeply influence marine biodiversity. In polar marine environments, where environmental conditions are characterized by low temperatures, the role of iron becomes particularly [...] Read more.

Iron is a key micronutrient essential for various essential biological processes. As a consequence, alteration in iron concentration in seawater can deeply influence marine biodiversity. In polar marine environments, where environmental conditions are characterized by low temperatures, the role of iron becomes particularly significant. While iron limitation can negatively influence primary production and nutrient cycling, excessive iron concentrations can lead to harmful algal blooms and oxygen depletion. Furthermore, the growth of certain phytoplankton species can be increased in high-iron-content environments, resulting in altered balance in the marine food web and reduced biodiversity. Although many chemical/physical methods are established for inorganic iron quantification, the determination of the bio-available iron in seawater samples is more suitably carried out using marine microorganisms as biosensors. Despite existing challenges, whole-cell biosensors offer other advantages, such as real-time detection, cost-effectiveness, and ease of manipulation, making them promising tools for monitoring environmental iron levels in polar marine ecosystems. In this review, we discuss fundamental biosensor designs and assemblies, arranging host features, transcription factors, reporter proteins, and detection methods. The progress in the genetic manipulation of iron-responsive regulatory and reporter modules is also addressed to the optimization of the biosensor performance, focusing on the improvement of sensitivity and specificity. Full article

(This article belongs to the Special Issue Polar Marine Bacteria: From Physiology to Biotechnological Applications)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Mar. Drugs, Volume 22, Issue 7 (July 2024) – 41 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI