Marine Drugs

11 pages, 1265 KiB

Open AccessArticle

Statins Diversity Revealed by the Deep-Sea-Derived Fungus Penicillium viridicatum

by Meng Zhang, Rong Chao, Jia-Jian Wang, Zi-Han Xu, Ji-Hong Zhang, Da-Li Meng, Tai-Zong Wu and Xian-Wen Yang

Mar. Drugs 2025, 23(2), 87; https://doi.org/10.3390/md23020087 - 17 Feb 2025

Abstract

Seven new (1–7) and six known (8–13) statin derivatives were obtained from the deep-sea-derived fungus Penicillium viridicatum MCCC 3A00265. The structures assigned to the new compounds were based on a comprehensive analysis of the spectroscopic [...] Read more.

Seven new (1–7) and six known (8–13) statin derivatives were obtained from the deep-sea-derived fungus Penicillium viridicatum MCCC 3A00265. The structures assigned to the new compounds were based on a comprehensive analysis of the spectroscopic data, with absolute configurations established by Mosher analysis and biogenetic consideration. Most of the new compounds (1–5 and 7) share an octohydronaphthalene backbone, except that viridecalin F (6) possesses an uncommon naphthalene core. Viridecalins C (3) and F (6) and the two known compounds 9 and 11 exhibit considerable ability in reactivating mutant p53 protein at 10 μM, while viridecalin C showcases the most potent reactivation activity, indicating the potential of application in cancer therapy. Full article

(This article belongs to the Special Issue Bioactive Natural Products from the Deep-Sea-Sourced Microbes)

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23 pages, 1204 KiB

Open AccessReview

Marine Phytoplankton Bioactive Lipids and Their Perspectives in Clinical Inflammation

by Edoardo Andrea Cutolo, Rosanna Campitiello, Valeria Di Dato, Ida Orefice, Max Angstenberger and Maurizio Cutolo

Mar. Drugs 2025, 23(2), 86; https://doi.org/10.3390/md23020086 - 17 Feb 2025

Abstract

Marine phytoplankton is an emerging source of immunomodulatory bioactive lipids (BLs). Under physiological growth conditions and upon stress challenges, several eukaryotic microalgal species accumulate lipid metabolites that resemble the precursors of animal mediators of inflammation: eicosanoids and prostaglandins. Therefore, marine phytoplankton could serve [...] Read more.

Marine phytoplankton is an emerging source of immunomodulatory bioactive lipids (BLs). Under physiological growth conditions and upon stress challenges, several eukaryotic microalgal species accumulate lipid metabolites that resemble the precursors of animal mediators of inflammation: eicosanoids and prostaglandins. Therefore, marine phytoplankton could serve as a biotechnological platform to produce functional BLs with therapeutic applications in the management of chronic inflammatory diseases and other clinical conditions. However, to be commercially competitive, the lipidic precursor yields should be enhanced. Beside tailoring the cultivation of native producers, genetic engineering is a feasible strategy to accrue the production of lipid metabolites and to introduce heterologous biosynthetic pathways in microalgal hosts. Here, we present the state-of-the-art clinical research on immunomodulatory lipids from eukaryotic marine phytoplankton and discuss synthetic biology approaches to boost their light-driven biosynthesis. Full article

(This article belongs to the Special Issue Lipidomics in Marine Microalgae and Seaweeds: Applications and Perspectives)

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21 pages, 10431 KiB

Open AccessArticle

Large-Scale AI-Based Structure and Activity Prediction Analysis of ShK Domain Peptides from Sea Anemones in the South China Sea

by Ziqiang Hua, Limin Lin, Wanting Yang, Linlin Ma, Meiling Huang and Bingmiao Gao

Mar. Drugs 2025, 23(2), 85; https://doi.org/10.3390/md23020085 - 16 Feb 2025

Abstract

Sea anemone peptides represent a valuable class of biomolecules in the marine toxin library due to their various structures and functions. Among these, ShK domain peptides are particularly notable for their selective inhibition of the Kv1.3 channel, holding great potential for applications in [...] Read more.

Sea anemone peptides represent a valuable class of biomolecules in the marine toxin library due to their various structures and functions. Among these, ShK domain peptides are particularly notable for their selective inhibition of the Kv1.3 channel, holding great potential for applications in immune regulation and the treatment of metabolic disorders. However, these peptides’ structural complexity and diversity have posed challenges for functional prediction. In this study, we compared 36 ShK domain peptides from four species of sea anemone in the South China Sea and explored their binding ability with Kv1.3 channels by combining molecular docking and dynamics simulation studies. Our findings highlight that variations in loop length, residue composition, and charge distribution among ShK domain peptides affect their binding stability and specificity. This work presents an efficient strategy for large-scale peptide structure prediction and activity screening, providing a valuable foundation for future pharmacological research. Full article

(This article belongs to the Special Issue Chemoinformatics for Marine Drug Discovery)

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41 pages, 1468 KiB

Open AccessReview

Omega-3 Fatty Acids for the Treatment of Bipolar Disorder Symptoms: A Narrative Review of the Current Clinical Evidence

by Evmorfia Psara, Sousana K. Papadopoulou, Maria Mentzelou, Gavriela Voulgaridou, Theophanis Vorvolakos, Thomas Apostolou and Constantinos Giaginis

Mar. Drugs 2025, 23(2), 84; https://doi.org/10.3390/md23020084 - 15 Feb 2025

Abstract

Background: Bipolar disorder is a chronic mental disease that is characterized by depressive and manic episodes. Antipsychotics and mood stabilizers are known therapies that work, but their restrictions and disadvantages resulted in the need for complementary and alternative therapies, such as natural compounds. [...] Read more.

Background: Bipolar disorder is a chronic mental disease that is characterized by depressive and manic episodes. Antipsychotics and mood stabilizers are known therapies that work, but their restrictions and disadvantages resulted in the need for complementary and alternative therapies, such as natural compounds. Omega-3 fatty acids, as basic ingredients of fishes and seafood, play crucial roles in brain development, function of brain membrane enzymes, learning, and many other instances, and their deficiency has been associated with many mental diseases, including bipolar disorder. Methods: The present narrative review aims to critically summarize and scrutinize the available clinical studies on the use of omega-3 fatty acids in the management and co-treatment of bipolar disorder episodes and symptoms. For this purpose, a thorough and in-depth search was performed in the most accurate scientific databases, e.g., PubMed., Scopus, Web of Science, Cochrane, Embase, and Google Scholar, applying effective and relevant keywords. Results: There are currently several clinical studies that assessed the effect of omega-3 fatty acids on the severity of BD symptoms. Some of them supported evidence for the potential beneficial impact of omega-3 fatty acids supplementation in the prevention and/or co-treatment of bipolar disorder severity and symptomatology. Nevertheless, a considerable number of clinical studies did not show high efficiency, rendering the existing data rather conflicting. The above may be ascribed to the fact that there is a high heterogeneity amongst the available clinical studies concerning the dosage, the administration duration, the combination of fatty acids administration, the method designs and protocols, and the study populations. Conclusion: Although the currently available clinical evidence seems promising, it is highly recommended to accomplish larger, long-term, randomized, double-blind, controlled clinical trials with a prospective design in order to derive conclusive results as to whether omega-fatty acids could act as a co-treatment agent or even as protective factors against bipolar disorder symptomatology. Drug design strategies could be developed to derive novel synthetic omega-3 fatty acids analogs, which could be tested for their potential to attenuate the severity of BD episodes and symptoms. Full article

(This article belongs to the Special Issue Sustainable Valorization of Seafood By-Products through Recovery of Valuable Bioactive Compounds 2nd Edition)

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25 pages, 1059 KiB

Open AccessArticle

Antiaging Potential of Lipophilic Extracts of Caulerpa prolifera

by Gonçalo P. Rosa, Maria Carmo Barreto, Ana M. L. Seca and Diana C. G. A. Pinto

Mar. Drugs 2025, 23(2), 83; https://doi.org/10.3390/md23020083 - 14 Feb 2025

Abstract

The cosmeceutical industry has increasingly turned its attention to marine macroalgae, recognizing their significant bioactive potential as sources of natural compounds for skincare applications. A growing number of products now incorporate extracts or isolated compounds from various macroalgae species. However, many species remain [...] Read more.

The cosmeceutical industry has increasingly turned its attention to marine macroalgae, recognizing their significant bioactive potential as sources of natural compounds for skincare applications. A growing number of products now incorporate extracts or isolated compounds from various macroalgae species. However, many species remain underexplored, highlighting a valuable opportunity for further research. Among these, Caulerpa prolifera (Forsskål) J.V. Lamouroux has emerged as a promising candidate for cosmeceutical applications. This study provides the most comprehensive phytochemical assessment of C. prolifera to date, revealing its potential as a source of bioactive extracts and compounds. The analysis identified key components of its lipophilic profile, predominantly saturated and unsaturated fatty acids, alongside di-(2-ethylhexyl) phthalate—an endocrine disruptor potentially biosynthesized or bioaccumulated by the algae. While the crude extract exhibited moderate tyrosinase inhibitory activity, its overall antioxidant capacity was limited. Fractionation of the extract, however, yielded subfractions with distinct bioactivities linked to changes in chemical composition. Notably, enhanced inhibitory activities against elastase and collagenase were observed in subfractions enriched with 1-octadecanol and only traces of phthalate. Conversely, antioxidant activity diminished with the loss of specific compounds such as β-sitosterol, erucic acid, nervonic acid, and lignoceric acid. This work advances the understanding of the relationship between the chemical composition of C. prolifera and its bioactivities, emphasizing its potential as a source of cosmeceutical ingredients, leading to a more comprehensive valorization of this macroalga. Full article

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

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25 pages, 4725 KiB

Open AccessArticle

Bioprospecting Bioactive Peptides in Halobatrachus didactylus Body Mucus: From In Silico Insights to Essential In Vitro Validation

by Marta Fernandez Cunha, Ezequiel R. Coscueta, María Emilia Brassesco, Frederico Almada, David Gonçalves and Maria Manuela Pintado

Mar. Drugs 2025, 23(2), 82; https://doi.org/10.3390/md23020082 - 13 Feb 2025

Abstract

Fish body mucus plays a protective role, especially in Halobatrachus didactylus, which inhabits intertidal zones vulnerable to anthropogenic contaminants. In silico predicted bioactive peptides were identified in its body mucus, namely, EDNSELGQETPTLR (HdKTLR), DPPNPKNL (HdKNL), PAPPPPPP (HdPPP), VYPFPGPLPN (HdVLPN), and PFPGPLPN (HdLPN). [...] Read more.

Fish body mucus plays a protective role, especially in Halobatrachus didactylus, which inhabits intertidal zones vulnerable to anthropogenic contaminants. In silico predicted bioactive peptides were identified in its body mucus, namely, EDNSELGQETPTLR (HdKTLR), DPPNPKNL (HdKNL), PAPPPPPP (HdPPP), VYPFPGPLPN (HdVLPN), and PFPGPLPN (HdLPN). These peptides were studied in vitro for bioactivities and aggregation behavior under different ionic strengths and pH values. Size exclusion chromatography revealed significant peptide aggregation at 344 mM and 700 mM ionic strengths at pH 7.0, decreasing at pH 3.0 and pH 5.0. Although none exhibited antimicrobial properties, they inhibited Pseudomonas aeruginosa biofilm formation. Notably, HdVLPN demonstrated potential antioxidant activity (ORAC: 1.560 μmol TE/μmol of peptide; ABTS: 1.755 μmol TE/μmol of peptide) as well as HdLPN (ORAC: 0.195 μmol TE/μmol of peptide; ABTS: 0.128 μmol TE/μmol of peptide). Antioxidant activity decreased at pH 5.0 and pH 3.0. Interactions between the peptides and mucus synergistically enhanced antioxidant effects. HdVLPN and HdLPN were non-toxic to Caco-2 and HaCaT cells at 100 μg of peptide/mL. HdPPP showed potential antihypertensive and antidiabetic effects, with IC₅₀ values of 557 μg of peptide/mL for ACE inhibition and 1700 μg of peptide/mL for α-glucosidase inhibition. This study highlights the importance of validating peptide bioactivities in vitro, considering their native environment (mucus), and bioprospecting novel bioactive molecules while promoting species conservation. Full article

(This article belongs to the Special Issue Proteomic Studies for the Identification and Characterization of Marine Bioactive Molecules)

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15 pages, 4887 KiB

Open AccessArticle

Screening of Potential Angiotensin-Converting Enzyme-Inhibitory Peptides in Squid (Todarodes pacificus) Skin Hydrolysates: Preliminary Study of Its Mechanism of Inhibition

by Mingyuan Li, Qianqian Liang, Yurui Zhang, Xin Jiang, Yuan Gu, Xin Song, Xichang Wang and Wenzheng Shi

Mar. Drugs 2025, 23(2), 81; https://doi.org/10.3390/md23020081 - 13 Feb 2025

Abstract

Background: Hypertension has been identified as a significant risk factor for cardiovascular disease. Given the prevalence of the adverse effects of angiotensin-converting enzyme-inhibitory (ACEI) drugs, natural and effective alternatives to these medications need to be identified. Methods: An investigative study was conducted to [...] Read more.

Background: Hypertension has been identified as a significant risk factor for cardiovascular disease. Given the prevalence of the adverse effects of angiotensin-converting enzyme-inhibitory (ACEI) drugs, natural and effective alternatives to these medications need to be identified. Methods: An investigative study was conducted to assess the ACEI capacity and structural characteristics of enzymatic hydrolysates with varying molecular weights derived from squid skin. The amino acid sequences of the enzymatic digests were analyzed via Nano LC-MS/MS and screened for peptides with ACEI activity using an in silico analysis. Furthermore, molecular docking was employed to investigate the interaction between potential ACEI peptides and ACE. Results: TPSH-V (MW < 1 kDa) exhibited the highest rate of ACEI, a property attributable to its substantial hydrophobic amino acid content. Additionally, TPSH-V exhibited high temperature and pH stability, indicative of regular ordering in its secondary structure. The binding modes of four potential novel ACEI peptides to ACE were predicted via molecular docking with the sequences of FHGLPAK, IIAPPERKY, RGLPAYE, and VPSDVEF, all of which can bind to the ACE active site via hydrogen bonding, with FHGLPAK, RGLPAYE, and VPSDVEF being able to coordinate with Zn²⁺. Conclusions: Squid skin constitutes a viable resource for the production of ACEI peptides. Full article

(This article belongs to the Special Issue Value-Added Products from Marine Fishes)

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13 pages, 1096 KiB

Open AccessArticle

Marmaricines A-C: Antimicrobial Brominated Pyrrole Alkaloids from the Red Sea Marine Sponge Agelas sp. aff. marmarica

by Diaa T. A. Youssef, Areej S. Alqarni, Ameen M. Almohammadi, Turki Abujamel and Lamiaa A. Shaala

Mar. Drugs 2025, 23(2), 80; https://doi.org/10.3390/md23020080 - 12 Feb 2025

Abstract

The Red Sea is the home of a rich diversity of sponge species with unique ecological adaptations that thrive in its saline, warm, and nutrient-poor waters. Red Sea sponges offer potential as sources of bioactive compounds and novel drugs. The organic extract of [...] Read more.

The Red Sea is the home of a rich diversity of sponge species with unique ecological adaptations that thrive in its saline, warm, and nutrient-poor waters. Red Sea sponges offer potential as sources of bioactive compounds and novel drugs. The organic extract of the Red Sea sponge Agelas sp. aff. marmarica was investigated for its antimicrobial constituents. Through bioassay-guided fractionation of the antimicrobial fraction of the extract on SiO₂ and Sephadex LH-20, as well as HPLC purification, three bioactive compounds, marmaricines A-C (1–3), were isolated. Structural elucidation of the compounds was performed using 1D (¹H and ¹³C) and 2D (COSY, HSQC, HMBC, and NOESY) NMR, as well as (+)-HRESIMS, leading to the identification of the compounds. The antimicrobial activities of the compounds were assessed through evaluation of their inhibition zones, MIC, MBC, and MFC, against Methicillin-Resistant Staphylococcus aureus (MRSA), Escherichia coli, and Candida albicans. Marmaricines A and B exhibited the strongest antibacterial effects against MRSA, with inhibition zones ranging from 14.00 to 15.00 mm, MIC values of 8 µg/mL, and MBC values of 16 µg/mL. In comparison, marmaracine C showed slightly weaker activity (inhibition zone: 12 mm, MIC: 16 µg/mL, MBC: 32 µg/mL). In terms of antifungal activity, marmaricines B and C demonstrated the greatest effect against C. albicans, with inhibition zones of 14–15 mm, MIC values of 8 µg/mL, and MFCs of 16 µg/mL. Interestingly, none of the compounds showed any inhibitory effect against E. coli. The results indicate that marmaricines A-C are selectively active against MRSA, and marmaricines B and C demonstrate potential against C. albicans, making them promising candidates for the development of novel antimicrobial agents targeting resistant pathogens. Full article

(This article belongs to the Special Issue Antimicrobial Compounds from Marine and Island Ecosystems: Exploration, Characterization, and Application)

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24 pages, 12035 KiB

Open AccessArticle

Proteomic Diversity of the Sea Anemone Actinia fragacea: Comparative Analysis of Nematocyst Venom, Mucus, and Tissue-Specific Profiles

by Ricardo Alexandre Barroso, Tomás Rodrigues, Alexandre Campos, Daniela Almeida, Francisco A. Guardiola, Maria V. Turkina and Agostinho Antunes

Mar. Drugs 2025, 23(2), 79; https://doi.org/10.3390/md23020079 - 11 Feb 2025

Abstract

Sea anemones (Actiniaria, Cnidaria) are promising targets for biomedical research, as they produce unique bioactive compounds, including toxins and antimicrobial peptides (AMPs). However, the diversity and mechanisms underlying their chemical defenses remain poorly understood. In this study, we investigate the proteomic profiles of [...] Read more.

Sea anemones (Actiniaria, Cnidaria) are promising targets for biomedical research, as they produce unique bioactive compounds, including toxins and antimicrobial peptides (AMPs). However, the diversity and mechanisms underlying their chemical defenses remain poorly understood. In this study, we investigate the proteomic profiles of the unexplored sea anemone Actinia fragacea by analyzing its venom nematocyst extract, tissues, and mucus secretion. A total of 4011 different proteins were identified, clustered into 3383 protein groups. Among the 83 putative toxins detected, actinoporins, neurotoxins, and phospholipase A2 were uncovered, as well as two novel zinc metalloproteinases with two specific domains (ShK) associated with potassium channel inhibition. Common Gene Ontology (GO) terms were related to immune responses, cell adhesion, protease inhibition, and tissue regeneration. Furthermore, 1406 of the 13,276 distinct peptides identified were predicted as potential AMPs, including a putative Aurelin-like AMP localized within the nematocysts. This discovery highlights and strengthens the evidence for a cnidarian-exclusive Aurelin peptide family. Several other bioactive compounds with distinctive defense functions were also detected, including enzymes, pattern recognition proteins (PRPs), and neuropeptides. This study provides the first proteome map of A. fragacea, offering a critical foundation for exploring novel bioactive compounds and valuable insights into its molecular complexity. Full article

(This article belongs to the Special Issue Chemical Defense in Marine Organisms, 3rd Edition)

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11 pages, 1931 KiB

Open AccessArticle

Geliboluols A–D: Kaurane-Type Diterpenoids from the Marine-Derived Rare Actinomycete Actinomadura geliboluensis

by Chang-Su Heo, Jong Soon Kang, Jeong-Wook Yang, Min Ah Lee, Hwa-Sun Lee, Chang Hwan Kim and Hee Jae Shin

Mar. Drugs 2025, 23(2), 78; https://doi.org/10.3390/md23020078 - 10 Feb 2025

Abstract

Four new kaurane-type diterpenoids, geliboluols A–D (1–4), along with one known analog (5), were isolated from the culture broth of the marine-derived rare actinomycete Actinomadura geliboluensis. The structures of compounds 1–4 were determined by [...] Read more.

Four new kaurane-type diterpenoids, geliboluols A–D (1–4), along with one known analog (5), were isolated from the culture broth of the marine-derived rare actinomycete Actinomadura geliboluensis. The structures of compounds 1–4 were determined by spectroscopic analysis (HR-ESIMS, 1D, and 2D NMR), the MPA method, and by comparing their optical rotation values with those in the literature. The new compounds were evaluated for their cytotoxicity against seven blood cancer cell lines by a CellTiter-Glo (CTG) assay and six solid cancer cell lines by a sulforhodamine B (SRB) assay. Among the new compounds, compound 4 exhibited moderate cytotoxic activity against some blood cancer cell lines, with GI₅₀ values ranging from 2.59 to 19.64 µM, and against solid cancer cell lines with GI₅₀ values ranging from 4.34 to 7.23 µM. Full article

(This article belongs to the Special Issue Marine-Derived Terpenes: Chemistry, Synthesis and Their Therapeutic Potential)

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23 pages, 1810 KiB

Open AccessArticle

Wound Healing, Antioxidant, and Antiviral Properties of Bioactive Polysaccharides of Microalgae Strains Isolated from Greek Coastal Lagoons

by Gabriel Vasilakis, Sofia Marka, Alexandros Ntzouvaras, Maria-Eleftheria Zografaki, Eirini Kyriakopoulou, Katerina I. Kalliampakou, Georgios Bekiaris, Evangelos Korakidis, Niki Papageorgiou, Stefania Christofi, Niki Vassilaki, Georgia Moschopoulou, Ioannis Tzovenis, Athena Economou-Amilli, Seraphim Papanikolaou and Emmanouil Flemetakis

Mar. Drugs 2025, 23(2), 77; https://doi.org/10.3390/md23020077 - 10 Feb 2025

Abstract

Microalgae have gained significant attention as sustainable sources of high value compounds, such as bioactive polysaccharides that are usually rich in sulfated groups and exhibit antioxidant properties. Here, 14 new microalgae strains of the genera Tetraselmis, Dunaliella, and Nannochloropsis, isolated from [...] Read more.

Microalgae have gained significant attention as sustainable sources of high value compounds, such as bioactive polysaccharides that are usually rich in sulfated groups and exhibit antioxidant properties. Here, 14 new microalgae strains of the genera Tetraselmis, Dunaliella, and Nannochloropsis, isolated from Greek coastal lagoons were analyzed to quantify and characterize their polysaccharide content. Heterogeneity was observed regarding the content of their total sugars (5.5–40.9 g/100 g dry biomass). The strains with a total sugar content above 20% were analyzed concerning the content of total, α- and β-glucans. Tetraselmis verrucosa f. rubens PLA1-2 and T. suecica T3-1 were rich in β-glucans (11%, and 8.1%, respectively). The polysaccharides of the two Tetraselmis strains were isolated and they were mainly composed of glucose and galactose. The isolated polysaccharides were fractionated using ion-exchange-chromatography. The anionic fraction from T. verrucosa f. rubens PLA1-2 was rich in sulfated polysaccharides, had antioxidant capacity, and exhibited healing properties. The anionic polysaccharides from the two Tetraselmis strains did not negatively influence the viability of human cells, while exhibiting antiviral properties against the replication of Hepatitis C Virus (HCV), with median efficient concentrations (EC50) at a range of 210–258 μg/mL. Full article

(This article belongs to the Special Issue The Extraction and Application of Functional Components in Algae)

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17 pages, 9845 KiB

Open AccessArticle

Integration of Transcriptomics and Proteomics to Elucidate Inhibitory Effect and Mechanism of Antifungalmycin B from Marine Streptomyces hiroshimensis in Treating Talaromyces marneffei

by Qiqi Li, Zhou Wang, Cuiping Jiang, Jianglin Yin, Yonghong Liu, Xinjian Qu, Xiangxi Yi and Chenghai Gao

Mar. Drugs 2025, 23(2), 76; https://doi.org/10.3390/md23020076 - 10 Feb 2025

Abstract

Talaromyces marneffei (TM) is an opportunistic pathogenic fungus that mainly infects immunocompromised patients. Currently, the global prevalence of talaromycosis caused by TM is increasing, leading to an increased demand for anti-TM drugs. In our previous study, a novel 28-membered macrolide compound, antifungalmycin B [...] Read more.

Talaromyces marneffei (TM) is an opportunistic pathogenic fungus that mainly infects immunocompromised patients. Currently, the global prevalence of talaromycosis caused by TM is increasing, leading to an increased demand for anti-TM drugs. In our previous study, a novel 28-membered macrolide compound, antifungalmycin B (ANB), was isolated from Streptomyces hiroshimensis GXIMD 06359, exhibiting significant antifungal properties. However, its in vivo mechanisms and direct antifungal effects warrant further investigation. In this study, we employed a mouse model in conjunction with transcriptomic and proteomic approaches to explore the antifungal activity of ANB against T. marneffei. In an in vivo mouse model infected with T. marneffei infection, ANB significantly reduced fungal burdens in the liver, spleen, lungs, and kidneys. Additionally, it markedly decreased the levels of reactive oxygen species (ROS) and cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. Proteomic and transcriptomic studies, complemented by parallel reaction monitoring (PRM) analysis, revealed that ANB effectively disrupted acid biosynthesis and cellular energy metabolism, thereby impairing mitochondrial functions in T. marneffei. These effects were exerted through multiple pathways. These findings highlight the potential of ANB as a versatile inhibitor of polyene macrolide-resistant fungi, offering a promising therapeutic avenue for the treatment of talaromycosis. Full article

(This article belongs to the Special Issue Novel Marine Antimicrobial Agents: Isolation, Synthesis, and Biological Evaluation)

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23 pages, 12666 KiB

Open AccessArticle

Preparation of Acetylcholinesterase Inhibitory Peptides from Yellowfin Tuna Pancreas Using Moderate Ultrasound-Assisted Enzymatic Hydrolysis

by Pai Peng, Hui Yu, Meiting Xian, Caiye Qu, Zhiqiang Guo, Shuyi Li, Zhenzhou Zhu and Juan Xiao

Mar. Drugs 2025, 23(2), 75; https://doi.org/10.3390/md23020075 - 9 Feb 2025

Abstract

Bioactive peptides represent a promising therapeutic approach for Alzheimer’s disease (AD) by maintaining cholinergic system homeostasis through the inhibition of acetylcholinesterase (AChE) activity. This study focused on extracting AChE inhibitory peptides from yellowfin tuna pancreas using moderate ultrasound-assisted enzymatic hydrolysis (MUE). Firstly, papain [...] Read more.

Bioactive peptides represent a promising therapeutic approach for Alzheimer’s disease (AD) by maintaining cholinergic system homeostasis through the inhibition of acetylcholinesterase (AChE) activity. This study focused on extracting AChE inhibitory peptides from yellowfin tuna pancreas using moderate ultrasound-assisted enzymatic hydrolysis (MUE). Firstly, papain and MUE stood out from five enzymes and four enzymatic hydrolysis methods, respectively, by comparing the degree of hydrolysis and AChE inhibitory activity of different pancreatic protein hydrolysates. Subsequently, the optimal MUE conditions were obtained by single-factor, Plackett–Burman, and response surface methodologies. The pancreatic protein hydrolysate prepared under optimal MUE conditions was then purified by ultrafiltration followed by RP-HPLC, from which a novel AChE inhibitory peptide (LLDF) was identified by LC-MS/MS and virtual screening. LLDF effectively inhibited AChE activity by a competitive inhibition mechanism, with an IC₅₀ of 18.44 ± 0.24 μM. Molecular docking and molecular dynamic simulation revealed that LLDF bound robustly to the active site of AChE via hydrogen bonds. These findings provided a theoretical basis for the valuable use of yellowfin tuna pancreas and introduced a new viewpoint on the potential therapeutic advantages of AChE inhibitory peptides for future AD treatment. Full article

(This article belongs to the Special Issue Enzyme Inhibitors from Marine Resources, 2nd Edition)

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18 pages, 10369 KiB

Open AccessArticle

TMF Attenuates Cognitive Impairment and Neuroinflammation by Inhibiting the MAPK/NF-κB Pathway in Alzheimer’s Disease: A Multi-Omics Analysis

by Yonglin Liu, Xi Xu, Xiaoming Wu, Guodong Yang, Jiaxin Luo, Xinli Liang, Jie Chen and Yiguang Li

Mar. Drugs 2025, 23(2), 74; https://doi.org/10.3390/md23020074 - 7 Feb 2025

Abstract

The rising prevalence of Alzheimer’s disease (AD) underscores the urgent need for novel therapeutic agents derived from natural sources. Among flavonoids, 3′,4′,5,7-tetramethoxyflavone (TMF), a structural analog of luteolin, has gained attention for its favorable pharmacokinetics and potential neuroprotective properties. Despite the significant neuroprotective [...] Read more.

The rising prevalence of Alzheimer’s disease (AD) underscores the urgent need for novel therapeutic agents derived from natural sources. Among flavonoids, 3′,4′,5,7-tetramethoxyflavone (TMF), a structural analog of luteolin, has gained attention for its favorable pharmacokinetics and potential neuroprotective properties. Despite the significant neuroprotective effects and favorable pharmacokinetics of TMF, its efficacy and mechanism of action in AD remain unclear. This study explored TMF’s pharmacological effects in AD models, highlighting its ability to improve memory and cognitive deficits in APP/PS1 mice. TMF reduced Aβ plaques, NFTs formation, and glial activation while suppressing neuroinflammation through the MAPK/NF-κB pathway. Further analysis in LPS-induced BV2 cells revealed TMF’s ability to reduce microglial activation. These findings highlight the anti-neuroinflammatory activity of TMF, suggesting its potential as a treatment for AD. Full article

(This article belongs to the Special Issue Marine Natural Products as Regulators in Cell Signaling Pathway)

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20 pages, 4758 KiB

Open AccessArticle

Integrated Macrogenomics and Metabolomics Analysis of the Effect of Sea Cucumber Ovum Hydrolysates on Dextran Sodium Sulfate-Induced Colitis

by Shunmin Gong, Liqin Sun, Yongjun Sun, Wenming Ju, Gongming Wang, Jian Zhang, Xuejun Fu, Chang Lu, Yu Zhang, Wenkui Song, Mingbo Li and Leilei Sun

Mar. Drugs 2025, 23(2), 73; https://doi.org/10.3390/md23020073 - 7 Feb 2025

Abstract

Inflammatory bowel disease remains a significant challenge in clinical settings. This study investigated the therapeutic potential of sea cucumber ovum hydrolysates (SCH) in a dextran sulfate sodium (DSS)-induced colitis mouse model. SCH, defined by its elevated stability and solubility, with a molecular weight [...] Read more.

Inflammatory bowel disease remains a significant challenge in clinical settings. This study investigated the therapeutic potential of sea cucumber ovum hydrolysates (SCH) in a dextran sulfate sodium (DSS)-induced colitis mouse model. SCH, defined by its elevated stability and solubility, with a molecular weight below 1000 Da, significantly alleviated DSS-induced colitis, as evidenced by enhanced splenic index, reduced colonic damage, and diminished serum pro-inflammatory cytokines. Furthermore, macrogenomic analysis demonstrated that SCH increased beneficial gut microbes and decreased pro-inflammatory bacteria. Furthermore, metabolomic analysis of colonic tissues identified elevated levels of anti-inflammatory metabolites, such as Phenyllactate, 2-Hydroxyglutarate, and L-Aspartic acid, in colitis mice after oral administration of SCH. In conclusion, SCH represents a promising candidate for the treatment of colitis. Full article

(This article belongs to the Special Issue Bioactive Proteins and Peptides from Marine Mollusks)

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52 pages, 6096 KiB

Open AccessReview

Marine-Derived Diterpenes from 2019 to 2024: Structures, Biological Activities, Synthesis and Potential Applications

by Lin Zhang, Debao Li, Xuan Chen and Feng Zhao

Mar. Drugs 2025, 23(2), 72; https://doi.org/10.3390/md23020072 - 7 Feb 2025

Abstract

Marine diterpenes are an important category of secondary metabolites derived from marine sources, found in a variety of marine animals, plants, and fungi. The increasing diversity of diterpene compounds, along with their unique chemical structures and specific biological activities, have attracted widespread attention. [...] Read more.

Marine diterpenes are an important category of secondary metabolites derived from marine sources, found in a variety of marine animals, plants, and fungi. The increasing diversity of diterpene compounds, along with their unique chemical structures and specific biological activities, have attracted widespread attention. These activities include anti-inflammatory, antiviral, antitumor, antibacterial effects, and therapeutic actions against cancer, with many already developed into clinical drugs. Additionally, as marine medicinal resources continue to be exploited over the long term, the natural resources of many marine diterpene compounds are diminishing, and the biosynthesis of key active components has become a hot topic of research. In this review, we summarize diterpene compounds discovered in the ocean over the past five years, reclassify these compounds, and summarize their structures, biological activities, biosynthesis, and potential applications of marine diterpenoids from 2019 to 2024. This review can provide a reference for the basic research and potential applications of marine-derived diterpene compounds. Full article

(This article belongs to the Special Issue Marine-Derived Terpenes: Chemistry, Synthesis and Their Therapeutic Potential)

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22 pages, 19510 KiB

Open AccessArticle

The Role of Brown Algae as a Capping Agent in the Synthesis of ZnO Nanoparticles to Enhance the Antibacterial Activities of Cotton Fabrics

by Eli Rohaeti, Helmiyati, Rasamimanana Joronavalona, Paulina Taba, Dewi Sondari and Azlan Kamari

Mar. Drugs 2025, 23(2), 71; https://doi.org/10.3390/md23020071 - 7 Feb 2025

Abstract

Research was conducted on the role of brown algae as a capping agent in the synthesis of ZnO nanoparticles, the characteristics of ZnO nanoparticles, and the effect of the addition of ZnO nanoparticles and/or silane compounds on antibacterial and antifungal activities. The synthesis [...] Read more.

Research was conducted on the role of brown algae as a capping agent in the synthesis of ZnO nanoparticles, the characteristics of ZnO nanoparticles, and the effect of the addition of ZnO nanoparticles and/or silane compounds on antibacterial and antifungal activities. The synthesis of ZnO nanoparticles involved green synthesis, and then nanoparticles were characterized using UV/VIS/NIR, ATR-FTIR, XRD, PSA, and SEM-EDS, followed by the in situ deposition of ZnO nanoparticles on cotton fabrics and the addition of silane compounds. The characterization of modified and unmodified cotton fabrics and antibacterial and antifungal activity tests were carried out using the disc diffusion method through measurements of the diameter of the inhibition zone against Pseudomonas aeruginosa, Staphylococcus epidermidis, and Malassezia furfur. The characterization of ZnO nanoparticles showed absorption at a wavelength of 357 nm; the number of waves was 450 cm⁻¹; the diffraction peak occurred at an angle of 36.14°; the crystal size was 15.35 nm; there was a heterogeneous particle distribution; the particle size was in the ranges of 1.74–706 nm (PSA) and 45–297 nm (SEM); and an irregular particle shape was noted. The results showed that the best antibacterial and antifungal activity was obtained in cotton + HDTMS + ZnO nanoparticles (K8) and cotton + ZnO nanoparticles+HDTMS/MTMS (K4). Full article

(This article belongs to the Special Issue Marine Algae: Exploring Their Nutritional, Health, and Nutraceutical Potential)

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24 pages, 1711 KiB

Open AccessReview

Anticancer Properties of Macroalgae: A Comprehensive Review

by Sara Frazzini and Luciana Rossi

Mar. Drugs 2025, 23(2), 70; https://doi.org/10.3390/md23020070 - 7 Feb 2025

Abstract

In recent years, the exploration of bioactive molecules derived from natural sources has gained interest in several application fields. Among these, macroalgae have garnered significant attention due to their functional properties, which make them interesting in therapeutic applications, including cancer treatment. Cancer constitutes [...] Read more.

In recent years, the exploration of bioactive molecules derived from natural sources has gained interest in several application fields. Among these, macroalgae have garnered significant attention due to their functional properties, which make them interesting in therapeutic applications, including cancer treatment. Cancer constitutes a significant global health burden, and the side effects of existing treatment modalities underscore the necessity for the exploration of novel therapeutic models that, in line with the goal of reducing drug treatments, take advantage of natural compounds. This review explores the anticancer properties of macroalgae, focusing on their bioactive compounds and mechanisms of action. The key findings suggest that macroalgae possess a rich array of bioactive compounds, including polysaccharides (e.g., fucoidans and alginates), polyphenols (e.g., phlorotannins), and terpenoids, which exhibit diverse anticancer activities, such as the inhibition of cell proliferation, angiogenesis, induction of apoptosis, and modulation of the immune system. This review provides an overview of the current understanding of macroalgae’s anticancer potential, highlighting the most promising compounds and their mechanisms of action. While preclinical studies have shown promising results, further research is necessary to translate these findings into effective clinical applications. Full article

(This article belongs to the Special Issue Marine Algae: Exploring Their Nutritional, Health, and Nutraceutical Potential)

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65 pages, 7602 KiB

Open AccessReview

Advanced Technologies for Large Scale Supply of Marine Drugs

by Henar Martínez, Mercedes Santos, Lucía Pedraza and Ana M. Testera

Mar. Drugs 2025, 23(2), 69; https://doi.org/10.3390/md23020069 - 7 Feb 2025

Abstract

Marine organisms represent a source of unique chemical entities with valuable biomedical potentialities, broad diversity, and complexity. It is essential to ensure a reliable and sustainable supply of marine natural products (MNPs) for their translation into commercial drugs and other valuable products. From [...] Read more.

Marine organisms represent a source of unique chemical entities with valuable biomedical potentialities, broad diversity, and complexity. It is essential to ensure a reliable and sustainable supply of marine natural products (MNPs) for their translation into commercial drugs and other valuable products. From a structural point of view and with few exceptions, MNPs of pharmaceutical importance derive from the so-called secondary metabolism of marine organisms. When production strategies rely on marine macroorganisms, harvesting or culturing coupled with extraction procedures frequently remain the only alternative to producing these compounds on an industrial scale. Their supply can often be implemented with laboratory scale cultures for bacterial, fungal, or microalgal sources. However, a diverse approach, combining traditional methods with modern synthetic biology and biosynthesis strategies, must be considered for invertebrate MNPs, as they are usually naturally accumulated in only very small quantities. This review offers a comprehensive examination of various production strategies for MNPs, addressing the challenges related to supply, synthesis, and scalability. It also underscores recent biotechnological advancements that are likely to transform the current industrial-scale manufacturing methods for pharmaceuticals derived from marine sources. Full article

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

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