Marine Drugs

15 pages, 2375 KiB

Open AccessArticle

Synthesis and Evaluation of Antitumor and Anti-Angiogenesis Activity of Pyrone- or Pyridone-Embedded Analogs of Cortistatin A

by Yuri Fujimoto, Kanako Mizuno, Yuta Nakamura, Masayoshi Arai and Naoyuki Kotoku

Mar. Drugs 2025, 23(4), 179; https://doi.org/10.3390/md23040179 - 20 Apr 2025

Viewed by 142

Abstract

Simplified analogs of cortistatin A were synthesized and biologically evaluated to develop novel antitumor substances that target angiogenesis. To analyze the effect of substituents at positions corresponding to C-2 and/or C-4 of the A-ring, various pyrone- or pyridone-embedded analogs were designed and synthesized. [...] Read more.

Simplified analogs of cortistatin A were synthesized and biologically evaluated to develop novel antitumor substances that target angiogenesis. To analyze the effect of substituents at positions corresponding to C-2 and/or C-4 of the A-ring, various pyrone- or pyridone-embedded analogs were designed and synthesized. Among the prepared analogs, the pyridone analog 19 bearing a methyl group at C-2 and a hydroxyl group at C-4 showed potent and selective growth inhibitory activity against human umbilical vein endothelial cells (HUVECs, IC₅₀ = 0.001 µM, selective index over that against human epidermoid carcinoma KB3-1 cells = 6400), exceeding those of natural products. The analog 19 of oral administration exhibited excellent in vivo antitumor activity in mice subcutaneously inoculated with sarcoma S180 cells. Full article

(This article belongs to the Special Issue Synthetic Studies of Marine Bioactive Natural Products and Analogs to Develop Novel Drug Leads)

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18 pages, 8998 KiB

Open AccessArticle

Synthesis and Evaluation of Aquatic Antimicrobial Peptides Derived from Marine Metagenomes Using a High-Throughput Screening Approach

by Kaiyue Wu, Guangxin Xu, Yin Tian, Guizhen Li, Zhiwei Yi and Xixiang Tang

Mar. Drugs 2025, 23(4), 178; https://doi.org/10.3390/md23040178 - 20 Apr 2025

Viewed by 163

Abstract

Bacterial diseases cause high mortality and considerable losses in aquaculture. The rapid expansion of intensive aquaculture has further increased the risk of large-scale outbreaks. However, the emergence of drug-resistant bacteria, food safety concerns, and environmental regulations have severely limited the availability of antimicrobial. [...] Read more.

Bacterial diseases cause high mortality and considerable losses in aquaculture. The rapid expansion of intensive aquaculture has further increased the risk of large-scale outbreaks. However, the emergence of drug-resistant bacteria, food safety concerns, and environmental regulations have severely limited the availability of antimicrobial. Compared to traditional antibiotics, antimicrobial peptides (AMPs) offer broad spectrum activity, physicochemical stability, and lower resistance development. However, their low natural yield and high extraction costs along with the time-consuming and expensive nature of traditional drug discovery, pose a challenge. In this study, we applied a machine-learning macro-model to predict AMPs from three macrogenomes in the water column of South American white shrimp aquaculture ponds. The AMP content per megabase in the traditional earthen pond (TC1) was 1.8 times higher than in the biofloc pond (ZA1) and 63% higher than in the elevated pond (ZP11). A total of 1033 potential AMPs were predicted, including 6 anionic linear peptides, 616 cationic linear peptides, and 411 cationic cysteine-containing peptides. After screening based on structural, and physio-chemical properties, we selected 10 candidate peptides. Using a rapid high-throughput cell-free protein expression system, we identified nine peptides with antimicrobial activity against aquatic pathogens. Three were further validated through chemical synthesis. The three antimicrobial peptides (K-5, K-58, K-61) showed some inhibitory effects on all four pathogenic bacteria. The MIC of K-5 against Vibrio alginolyticus was 25 μM, the cell viability of the three peptides was higher than 70% at low concentrations (≤12.5 μM), and the hemolysis rate of K-5 and K-58 was lower than 5% at 200 μM. This study highlights the benefits of machine learning in AMP discovery, demonstrates the potential of cell-free protein synthesis systems for peptide screening, and provides an efficient method for high-throughput AMP identification for aquatic applications. Full article

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18 pages, 3560 KiB

Open AccessArticle

Exploring the In Vivo Fate of β-1, 3/1, 6-Glucan Using Quantitative Tandem Mass Spectrometry Based on a Structure-Specific Fragment

by Shuying Xu, Jiale Hao, Chunyan Ye, Xintong Li, Pengcheng Gao, Ni Song, Chanjuan Liu, Youjing Lv, Guangli Yu and Guoyun Li

Mar. Drugs 2025, 23(4), 177; https://doi.org/10.3390/md23040177 - 20 Apr 2025

Viewed by 113

Abstract

β-glucan, a promising drug candidate for immuno-antitumor therapy, holds tremendous potential for clinical applications. However, the absence of highly sensitive quantitative methods for polysaccharides, attributed to their complicated chemical structures and susceptibility to endogenous interference, has posed significant challenges for their clinical development. [...] Read more.

β-glucan, a promising drug candidate for immuno-antitumor therapy, holds tremendous potential for clinical applications. However, the absence of highly sensitive quantitative methods for polysaccharides, attributed to their complicated chemical structures and susceptibility to endogenous interference, has posed significant challenges for their clinical development. Here, we report a highly sensitive and reliable analytical strategy for quantifying β-1, 3/1, 6-glucan derived from Durvillaea antarctica (BG136) in various biological matrices. This approach integrates targeted depolymerization and derivatization, followed by oligosaccharide isomer fingerprinting using ultra-high-performance liquid chromatography-triple quadrupole tandem mass spectrometry (UHPLC-MS/MS). The absolute quantification of BG136 relied on the abundance of the structure-specific trisaccharide (Glc-β1, 6-Glc-β1, 3-Glc) generated. This methodology not only facilitates prototype-based BG136 administration but also exhibits remarkable sensitivity. Following method optimization and validation, we successfully explored the in vivo fate of BG136 across multiple models, including cellular uptake and release kinetics, as well as preclinical and clinical pharmacokinetics. These achievements provide insight into the “black box” of BG136 from administration to elimination in vivo. This work marks the first practical application of this strategy in complex biological matrices, offering methodological support for the successful execution of the BG136 Phase I clinical trial. Full article

(This article belongs to the Special Issue Marine Polysaccharides and Oligosaccharides: Extraction and Biological Activities)

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20 pages, 17520 KiB

Open AccessArticle

The Identification and Characterization of a Novel Alginate Lyase from Mesonia hitae R32 Exhibiting High Thermal Stability and Potent Antioxidant Oligosaccharide Production

by Yongshang Ye, Zhiyu Li, Ying Zhou, Xiujun Gao and Dingfan Yan

Mar. Drugs 2025, 23(4), 176; https://doi.org/10.3390/md23040176 - 17 Apr 2025

Viewed by 168

Abstract

Alginate lyases are of great importance in biotechnological and industrial processes, yet research on these enzymes from Mesonia genus bacteria is still limited. In this study, a novel PL6 family alginate lyase, MhAly6, was cloned and characterized from the deep-sea bacterium Mesonia hitae [...] Read more.

Alginate lyases are of great importance in biotechnological and industrial processes, yet research on these enzymes from Mesonia genus bacteria is still limited. In this study, a novel PL6 family alginate lyase, MhAly6, was cloned and characterized from the deep-sea bacterium Mesonia hitae R32. The enzyme, composed of 797 amino acids, contains both PL6 and GH28 catalytic domains. A phylogenetic analysis revealed its classification into subfamily 1 of the PL6 family. MhAly6 showed optimal activity at 45 °C and pH 9.0, retaining over 50% activity after 210 min of incubation at 40 °C, highlighting its remarkable thermal stability. The enzyme exhibited degradation activity toward sodium alginate, Poly M, and Poly G, with the highest affinity for its natural substrate, sodium alginate, producing alginate oligosaccharides (AOSs) with degrees of polymerization (DP) ranging from 2 to 7. Molecular docking identified conserved catalytic sites (Lys241/Arg262) and Ca²⁺ binding sites (Asn202/Glu234/Glu236), while the linker and GH28 domain played an auxiliary role in substrate binding. Antioxidant assays revealed that the MhAly6-derived AOSs showed potent radical-scavenging activity, achieving 80.64% and 95.39% inhibition rates against DPPH and ABTS radicals, respectively. This work not only expands our understanding of alginate lyases from the Mesonia genus but also highlights their biotechnological potential for producing functional AOSs with antioxidant properties, opening new avenues for their applications in food and pharmaceuticals. Full article

(This article belongs to the Special Issue Marine Proteins and Enzymes: Bioactivities and Medicinal Applications)

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26 pages, 8897 KiB

Open AccessArticle

Epicoccin A Ameliorates PD-like Symptoms in Zebrafish: Enhancement of PINK1/Parkin-Dependent Mitophagy and Inhibition of Excessive Oxidative Stress

by Haicheng Ye, Dan Li, Lei Zhang, Yufei Wang, Cong Wang, Meng Jin, Houwen Lin, Peihai Li, Chen Sun and Ning Li

Mar. Drugs 2025, 23(4), 175; https://doi.org/10.3390/md23040175 - 17 Apr 2025

Viewed by 282

Abstract

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder, yet effective agents for its prevention and therapy remain highly limited. Epicoccin A, a significant secondary metabolite from Exserohilum sp., demonstrates various biological activities; however, its neuroprotective effects have not been elucidated. Here, [...] Read more.

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder, yet effective agents for its prevention and therapy remain highly limited. Epicoccin A, a significant secondary metabolite from Exserohilum sp., demonstrates various biological activities; however, its neuroprotective effects have not been elucidated. Here, we investigated the therapeutic potential of epicoccin A for PD by evaluating its impact on neural phenotype, reactive oxygen species (ROS) generation, and locomotor activity in PD-like zebrafish. Transcriptomic analysis and molecular docking were conducted, with key gene expressions further verified using real-time qPCR. As a result, epicoccin A notably mitigated dopaminergic neuron loss, neural vasculature deficiency, nervous system injury, ROS accumulation, locomotor impairments, and abnormal expressions of hallmark genes associated with PD and oxidative stress. Underlying mechanism investigation indicated epicoccin A may alleviate PD-like symptoms by activating PINK1/Parkin-dependent mitophagy, as evidenced by the reversal of aberrant gene expressions related to the pink1/parkin pathway and its upstream mTOR/FoxO pathway following epicoccin A co-treatments. This finding was further confirmed by the robust interactions between epicoccin A and these mitophagy regulators. Our results suggest that epicoccin A relieves PD symptoms by activating pink1/parkin-dependent mitophagy and inhibiting excessive oxidative stress, highlighting its potential as a therapeutic approach for PD. Full article

(This article belongs to the Special Issue Marine-Derived Bioactive Compounds for Neuroprotection)

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15 pages, 3538 KiB

Open AccessArticle

Rational High-Throughput System for Screening Emodin High-Yielding Mutant from Marine Strains of Aspergillus flavipes HN4-13

by Lizhi Gong, Zixuan Li, Meina Xu, Yushan Zhou, Wenqing Zhang, Jian Zhao, Xiujuan Xin and Faliang An

Mar. Drugs 2025, 23(4), 174; https://doi.org/10.3390/md23040174 - 16 Apr 2025

Viewed by 153

Abstract

Emodin is an anthraquinone compound known for its diverse biological activities, including anti-tumor and anti-inflammatory effects, making it highly applicable in the fields of biology and medicine. The production of emodin using microorganisms represents a sustainable and environmentally friendly approach. A marine-derived Aspergillus [...] Read more.

Emodin is an anthraquinone compound known for its diverse biological activities, including anti-tumor and anti-inflammatory effects, making it highly applicable in the fields of biology and medicine. The production of emodin using microorganisms represents a sustainable and environmentally friendly approach. A marine-derived Aspergillus flavipes HN4-13 was found to produce emodin, but the yield was too low for industrial production. To develop a high-yielding emodin-producing strain, we established the high-through detection and screening methods of alkaline coloration and deep-well plant culture, enabling the effective selection of high-yielding strains. Following ARTP mutagenesis of the wild strain A. flavipes HN4-13, the resulting mutant strain, M1440, exhibited an increased emodin yield of 124.6 ± 4.95 mg/L. Furthermore, the production of the emodin was enhanced by the exogenous addition of metal ions Mn²⁺ to the medium. Specifically, the addition of 3 mM Mn²⁺ resulted in a 133.2% increase in emodin production, with the highest yield reaching 178.6 ± 7.80 mg/L. Full article

(This article belongs to the Special Issue Marine Biorefinery for Bioactive Compounds Production)

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26 pages, 21610 KiB

Open AccessArticle

Effects of Amphidinium carterae Phytocompounds on Proliferation and the Epithelial–Mesenchymal Transition Process in T98G Glioblastoma Cells

by Julia Oyón Díaz de Cerio, Giulia Venneri, Ida Orefice, Martina Forestiero, Carlos Roman Baena, Gianluca Bruno Tassone, Isabella Percopo, Angela Sardo, Maria Luisa Panno, Francesca Giordano and Valeria Di Dato

Mar. Drugs 2025, 23(4), 173; https://doi.org/10.3390/md23040173 - 16 Apr 2025

Viewed by 372

Abstract

Glioblastoma (GBM) is an aggressive type of brain cancer, frequently invasive, with a low survival rate and complicated treatment. Recent studies have shown the modulation of epithelial–mesenchymal transition (EMT) biomarkers in glioblastoma cells associated with tumor progression, chemoresistance, and relapse after treatment. GBM [...] Read more.

Glioblastoma (GBM) is an aggressive type of brain cancer, frequently invasive, with a low survival rate and complicated treatment. Recent studies have shown the modulation of epithelial–mesenchymal transition (EMT) biomarkers in glioblastoma cells associated with tumor progression, chemoresistance, and relapse after treatment. GBM handlings are based on aggressive chemical therapies and surgical resection with poor percentage of survival, boosting the search for more specific remedies. Marine eukaryotic microalgae are rapidly advancing as a source of anticancer drugs due to their ability to produce potent secondary metabolites with biological activity. Among such microalgae, dinoflagellates, belonging to the species Amphidinium carterae, are known producers of neurotoxins and cytotoxic compounds. We tested the capability of chemical extracts from two different strains of A. carterae to modulate the EMT markers in T98G, human GBM cells. In vitro proliferation and migration studies and EMT biomarkers’ abundance and modulation assays showed that the different A. carterae strains differently modulated both EMT markers and the proliferation/migration capability of GBM cells. This study sets the bases to find a marine microalgae-derived natural compound that could potentially target the epithelial–mesenchymal transition in brain-derived tumor types. Full article

(This article belongs to the Special Issue Metabolites in Marine Planktonic Organisms)

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20 pages, 3069 KiB

Open AccessArticle

Cynthichlorine Extracted from Ascidian Cynthia savignyi from Djibouti: Optimization of Extraction, In Vitro Anticancer Profiling, and In Silico Approach

by Fatouma Mohamed Abdoul-Latif, Houda Mohamed, Ibrahim Houmed Aboubaker, Omaima Saoudi, Ayoub Ainane, Ali Merito Ali, Stefano Cacciatore, Luiz Fernando Zerbini, Abdelmjid Abourriche and Tarik Ainane

Mar. Drugs 2025, 23(4), 172; https://doi.org/10.3390/md23040172 - 16 Apr 2025

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Abstract

This work focuses on the extraction of cynthichlorine from the ascidian Cynthia savignyi, a molecule that has potential promise as an anticancer agent. The main objective was to optimize the extraction conditions and evaluate the cytotoxic activity of cynthichlorine in tumor cell [...] Read more.

This work focuses on the extraction of cynthichlorine from the ascidian Cynthia savignyi, a molecule that has potential promise as an anticancer agent. The main objective was to optimize the extraction conditions and evaluate the cytotoxic activity of cynthichlorine in tumor cell lines. Two extraction methods, maceration and Soxhlet extraction, were compared, with maceration showing a significantly higher yield (2.2 ± 0.2%) compared to Soxhlet extraction (1.0 ± 0.2%). An optimization of the factors influencing the extraction was performed using the Box–Behnken method, showing that the extraction temperature and time have a negative impact on the yield, with the optimal conditions of temperature being below 25 °C and those of extraction time being below 12 h. Cytotoxic activity assessment revealed the marked inhibition of cell growth in all tested lines (U87-MG, U2OS, NCI-N87, HCT116, and A2780), with IC₅₀ values ranging from 0.162 µg/mL in U87-MG to 0.576 µg/mL in NCI-N87. Finally, computational analysis showed that cynthichlorine exhibits high electronic stability and notable affinity for some biological targets, including NM23-H2, suggesting its potential as a targeted therapy in cancer treatment. These results pave the way for future studies on the therapeutic use of cynthichlorine. Full article

(This article belongs to the Special Issue Discovery, Synthesis and Mechanism of Marine Drugs for Treating Cancer)

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19 pages, 1009 KiB

Open AccessReview

Recent Advances in Research on Inhibitory Effects of Seaweed Extracts Against Parasites

by Wenbing Cheng, Xiangyang Yang, Dengfeng Yang, Ting Zhang, Liguang Tian, Jiahao Dao, Zheng Feng and Wei Hu

Mar. Drugs 2025, 23(4), 171; https://doi.org/10.3390/md23040171 - 16 Apr 2025

Viewed by 243

Abstract

Parasitic diseases pose a serious threat to the health of humans and the steady development of livestock husbandry. Although there are certain drug-based treatment methods, with the widespread application of drugs, various parasites are gradually developing drug resistance. Natural products are highly favored [...] Read more.

Parasitic diseases pose a serious threat to the health of humans and the steady development of livestock husbandry. Although there are certain drug-based treatment methods, with the widespread application of drugs, various parasites are gradually developing drug resistance. Natural products are highly favored by researchers due to their characteristics such as low toxicity, multi-target effects, and low risk of drug resistance. The ocean, as the largest treasure trove of biological resources on Earth, has a special ecosystem (high pressure, high salt, and low oxygen). This enables marine organisms to develop a large number of unique structures during their survival competition. So far, a variety of compounds, such as terpenoids, have been isolated from the algae. As potential drugs, these compounds have certain curative effects on various diseases, including tumors, parasitic diseases, Alzheimer’s disease, and tuberculosis. This paper systematically reviews and analyzes the current advances in research on the antiparasite effects of seaweed extracts. The primary objective of this research is to formulate a conceptual foundation for marine pharmaceutical exploration, focusing on the creation of innovative marine-based medicinal compounds to overcome the emerging problem of parasite resistance to conventional treatments. Full article

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

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12 pages, 1713 KiB

Open AccessArticle

Antibacterial Methyl Ester Cembranoids from the Soft Coral Sarcophyton ehrenbergi and Their Structural Elucidation

by Meng-Jun Wu, Song-Wei Li, Fei Xu, Ming-Zhi Su and Yue-Wei Guo

Mar. Drugs 2025, 23(4), 170; https://doi.org/10.3390/md23040170 - 15 Apr 2025

Viewed by 213

Abstract

Six previously undescribed methyl ester cembranoids, namely sarcoehrenolides L–Q (1–6), along with three known related ones (7–9), were isolated from the soft coral Sarcophyton ehrenbergi collected off Weizhou Island in the South China Sea. Their [...] Read more.

Six previously undescribed methyl ester cembranoids, namely sarcoehrenolides L–Q (1–6), along with three known related ones (7–9), were isolated from the soft coral Sarcophyton ehrenbergi collected off Weizhou Island in the South China Sea. Their structures and absolute configurations were unambiguously established in the light of extensive spectroscopic data analysis, X-ray diffraction analysis, chemical conversion, and TDDFT-ECD calculations. All isolated compounds were evaluated via in vitro bioassays to investigate their antibacterial activity against eighteen human and fish pathogens. Compounds 2, 8, and 9 exhibited moderate antibacterial activity against Streptococcus parauberis with MIC values of 38.8, 37.4 and 31.6 μg/mL, respectively. Full article

(This article belongs to the Special Issue Celebrating the 100th Anniversary of Ocean University of China: Potential Therapeutic Benefits of Marine Novel Natural Products)

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16 pages, 3022 KiB

Open AccessArticle

Insights into the Mechanism Underpinning Composite Molecular Docking During the Self-Assembly of Fucoidan Biopolymers with Peptide Nanofibrils

by Rui Li, Min-Rui Tai, Xian-Ni Su, Hong-Wu Ji, Jian-Ping Chen, Xiao-Fei Liu, Bing-Bing Song, Sai-Yi Zhong, David. R. Nisbet, Colin J. Barrow and Richard J. Williams

Mar. Drugs 2025, 23(4), 169; https://doi.org/10.3390/md23040169 - 15 Apr 2025

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Abstract

Composite hydrogels with improved mechanical and chemical properties can be formed by non-covalently decorating the nanofibrillar structures formed by the self-assembly of peptides with fucoidan. Nevertheless, the precise interactions, and the electrochemical and thermodynamic stability of these composite materials have not been determined. [...] Read more.

Composite hydrogels with improved mechanical and chemical properties can be formed by non-covalently decorating the nanofibrillar structures formed by the self-assembly of peptides with fucoidan. Nevertheless, the precise interactions, and the electrochemical and thermodynamic stability of these composite materials have not been determined. Here, we present a thermodynamic analysis of the interacting forces that drive the formation of a composite fucoidan/9-fluorenylmethoxycarbonyl-phenylalanine-arginine-glycine-aspartic acid-phenylalanine (Fmoc-FRGDF) hydrogel. The results showed that the co-assembly of fucoidan and Fmoc-FRGDF was spontaneous and exothermic. The melting point increased from 87.0 °C to 107.7 °C for Fmoc-FRGDF with 8 mg/mL of added fucoidan. A complex network of hydrogen bonds formed between the molecules of Fmoc-FRGDF, and electrostatic, hydrogen bond, and van der Waals interactions were the main interactions driving the co-assembly of fucoidan and Fmoc-FRGDF. Furthermore, the sulfate group of fucoidan formed a strong salt bridge with the arginine of Fmoc-FRGDF. This study provides useful biomedical engineering design parameters for the inclusion of other highly soluble biopolymers into these types of hydrogel vectors. Full article

(This article belongs to the Special Issue Marine Polysaccharides-Based Biomaterials)

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11 pages, 2869 KiB

Open AccessArticle

An Orthogonal Protection Strategy for the Synthesis of Conotoxins Containing Three Disulfide Bonds

by Hengyu Zhang, Lai Yue Chan, Huanhuan Zhang, Tao Jiang, David J. Craik, Wenqing Cai and Rilei Yu

Mar. Drugs 2025, 23(4), 168; https://doi.org/10.3390/md23040168 - 14 Apr 2025

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Abstract

Disulfide bonds are crucial for stabilizing bioactive peptides such as conotoxins. We have developed a method for synthesizing conotoxins with three disulfide bonds using Mob, Trt, and Acm protection groups for regionally selective synthesis. This approach enabled the efficient synthesis of peptides with [...] Read more.

Disulfide bonds are crucial for stabilizing bioactive peptides such as conotoxins. We have developed a method for synthesizing conotoxins with three disulfide bonds using Mob, Trt, and Acm protection groups for regionally selective synthesis. This approach enabled the efficient synthesis of peptides with the desired disulfide bond connectivities independent of their sequences. Using our strategy, we synthesized five conotoxins, achieving yields of 20–30%. The results demonstrate the potential of our method for synthesizing complex peptides with multiple disulfide bonds. Full article

(This article belongs to the Special Issue Conotoxins: Detection, Classification and Potential Therapeutic Benefits)

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18 pages, 8249 KiB

Open AccessArticle

Extracts from Allium pseudojaponicum Makino Target STAT3 Signaling Pathway to Overcome Cisplatin Resistance in Lung Cancer

by Soo-Bin Nam, Jung Hoon Choi, Ga-Eun Lee, Jin Young Kim, Mee-Hyun Lee, Gabsik Yang, Yong-Yeon Cho, Hye Gwang Jeong, Geul Bang and Cheol-Jung Lee

Mar. Drugs 2025, 23(4), 167; https://doi.org/10.3390/md23040167 - 14 Apr 2025

Viewed by 290

Abstract

Lung cancer, particularly non-small-cell lung cancer (NSCLC), remains a leading cause of cancer-related mortality, with cisplatin-based chemotherapy being a standard treatment. However, the development of chemoresistance significantly limits its efficacy, necessitating alternative therapeutic approaches. Here, we demonstrate the anticancer effects of the extracts [...] Read more.

Lung cancer, particularly non-small-cell lung cancer (NSCLC), remains a leading cause of cancer-related mortality, with cisplatin-based chemotherapy being a standard treatment. However, the development of chemoresistance significantly limits its efficacy, necessitating alternative therapeutic approaches. Here, we demonstrate the anticancer effects of the extracts of Allium pseudojaponicum Makino (APE), a salt-tolerant plant, in cisplatin-resistant NSCLC. Metabolite profiling using UPLC-Q-TOF-MS^E identified 13 major compounds, predominantly alkaloids (71.65%) and flavonoids (8.81%), with key bioactive constituents such as lycorine (29.81%), tazettine (17.22%), and tricetin (8.19%). APE significantly inhibited cell viability in A549 and H460 cells, reducing viability to 38.6% (A549-Ctr), 37.2% (A549-CR), 28.4% (H460-Ctr), and 30.4% (H460-CR) at 40 µg/mL after 48 h. APE also suppressed colony formation by over 90% in both 2D and soft agar assays, while showing no cytotoxicity in normal human keratinocytes up to 80 µg/mL. Flow cytometry analysis revealed APE-induced G1 phase arrest, with the G1 population increasing from 50.4% to 56.6% (A549-Ctr) and 47.5% to 58.4% (A549-CR), accompanied by reduced S phase populations. This effect was associated with the downregulation of G1/S transition regulators, including cyclin D1, CDK4, cyclin E, and CDK2. Furthermore, proteomic analysis identified STAT3 signaling as a major target of APE; APE decreased phosphorylated STAT3 and c-Myc expression, and STAT3 knockdown phenocopied the effects of APE. These findings highlight the potential of APE as a natural product-based therapeutic strategy for overcoming cisplatin resistance in NSCLC. Full article

(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents, 4th Edition)

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20 pages, 3238 KiB

Open AccessArticle

Advanced Strategies for Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Production: PHA Synthase Homologous Overexpression in the Extremophile Haloferax mediterranei

by Alexandra Simica, Yolanda Segovia, Alicia Navarro-Sempere, Rosa María Martínez-Espinosa and Carmen Pire

Mar. Drugs 2025, 23(4), 166; https://doi.org/10.3390/md23040166 - 11 Apr 2025

Viewed by 322

Abstract

Bioplastics such as poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) are promising alternatives to conventional plastics. However, the high production cost limits their industrial application. In this study, PHBV production was optimized in Haloferax mediterranei by the homologous overexpression of the key enzyme PHA synthase (PhaEC), resulting in [...] Read more.

Bioplastics such as poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) are promising alternatives to conventional plastics. However, the high production cost limits their industrial application. In this study, PHBV production was optimized in Haloferax mediterranei by the homologous overexpression of the key enzyme PHA synthase (PhaEC), resulting in the OEphaEC strain. The growth and PHBV production of OEphaEC compared with the parental strain (HM26) were evaluated in three culture media with different nitrogen sources (KNO₃, NH₄Cl, and casamino acids). The OEphaEC strain exhibited a 20% increase in PHBV production and a 40% increase in 3-hydroxyvalerate monomer (3HV) content in a defined medium with nitrate as a nitrogen source, as determined by GC-MS. Moreover, enzyme activity, measured spectrophotometrically, increased from 2.3 to 3.9 U/mg. Soluble and insoluble protein fractions were analysed to assess the overexpression of PHA synthase. Only PhaE was found in the insoluble protein fraction, where PHBV granules accumulate. Transmission electron microscopy (TEM) images confirmed a higher PHBV content in OEphaEC compared to the parental strain. These results demonstrate that the homologous overexpression of the key enzyme implicated in PHBV biosynthesis can enhance PHBV content, making its production competitive for industrial applications. Full article

(This article belongs to the Special Issue Marine Extremophiles: Adaptations and Biotechnological Applications)

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22 pages, 3728 KiB

Open AccessReview

Unveiling the Anti-Aging Potential of Marine Natural Bioproducts

by Nedeljka Rosic

Mar. Drugs 2025, 23(4), 165; https://doi.org/10.3390/md23040165 - 11 Apr 2025

Viewed by 477

Abstract

Aging is a natural process resulting in the progressive impairment of multiple functions in the human body, leading to a decline in cellular functionality and the development of aging-related diseases. External stress factors, such as ultraviolet (UV) radiation, pollution, and toxin exposure, increase [...] Read more.

Aging is a natural process resulting in the progressive impairment of multiple functions in the human body, leading to a decline in cellular functionality and the development of aging-related diseases. External stress factors, such as ultraviolet (UV) radiation, pollution, and toxin exposure, increase oxidative stress, damage cellular repair mechanisms, and speed up aging processes. With the rise in the world’s aging population, there are enlarged demands for the use of sustainable natural products in food, nutrient supplements and cosmetics that can slow down aging and prolong healthy life and longevity. Algae, including both macroalgae and microalgae, have been recognised as a source of valuable proteins, amino acids, fatty acids, vitamins, and minerals useful for human consumption and medical applications. With increasing demands for nutraceutical and pharmaceutical bioproducts from environmentally friendly resources, the biotechnological industry, over recent decades, has had to provide new, advanced solutions using modern high-throughput omics technologies. The application of proteomics in the area of discoveries of natural products with anti-aging properties has become more popular for wide industry applications. New proteomics profiling provides a better understanding of changes occurring in protein and peptide content, their structure, function and interactions, as well as the regulatory processes and molecular pathways. Mass spectrometry-based proteomics has been used for a wide range of applications including protein identification, characterisation, as well as quantification of proteins within the proteome and sub-proteome. The application of chemical proteomics facilitated the identification of natural products approach and included the synthesis of probes and target fishing, allowing the advanced identification of proteins of interest. This review focuses on marine macro- and microalgal anti-aging compounds and novel proteomics approaches, providing recent experimental evidence of their involvement in anti-aging processes that should facilitate their use in innovative approaches and sustainable biotechnological applications. Full article

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

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28 pages, 7480 KiB

Open AccessArticle

Effect of Heterologous Expression of Key Enzymes Involved in Astaxanthin and Lipid Synthesis on Lipid and Carotenoid Production in Aurantiochytrium sp.

by Yaping Shao, Zhengquan Gao, Fengjie Sun, Yulin Cui, Xinyu Zou, Jinju Ma, Qiaolei Wang, Hao Zhang, Yuyong Wu and Chunxiao Meng

Mar. Drugs 2025, 23(4), 164; https://doi.org/10.3390/md23040164 - 11 Apr 2025

Viewed by 375

Abstract

Aurantiochytrium sp., a heterotrophic microorganism, has received increasing attention for its high production of polyunsaturated fatty acids and has been widely applied in various industries. This study intended to optimize the carotenoid synthesis pathway in Aurantiochytrium sp. by metabolic engineering to increase the [...] Read more.

Aurantiochytrium sp., a heterotrophic microorganism, has received increasing attention for its high production of polyunsaturated fatty acids and has been widely applied in various industries. This study intended to optimize the carotenoid synthesis pathway in Aurantiochytrium sp. by metabolic engineering to increase the carotenoid content. Multi-sourced key enzyme genes involved in lipid synthesis (LPAAT and DGAT) and astaxanthin synthesis (crtZ and crtW) were selected to construct single-gene expression vectors and transformed into Aurantiochytrium sp. The results showed that the overexpression of LPAAT of Phaeodactylum tricornutum in Aurantiochytrium sp. caused an increase of 39.3% in astaxanthin, 424.7% in β-carotene, 901.8% in canthaxanthin, and 575.9% in lutein, as well as a down-regulation of 15.3% in the fatty acid content. Transcriptomics analysis revealed enhanced expression of genes involved in purine and amino acid metabolism in the transformed strains, and the down-regulation of the citric acid cycle led to an increase in the source of acetyl coenzyme A for the production of fatty acids. This study provides strong experimental evidence to support the application of increasing carotenoid levels in Aurantiochytrium sp. Full article

(This article belongs to the Special Issue Synthetic Biology in Marine Microalgae)

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26 pages, 1785 KiB

Open AccessReview

Therapeutic Prospects of Undaria pinnatifida Polysaccharides: Extraction, Purification, and Functional Activity

by Kit-Leong Cheong, Wenjie Chen, Min Wang, Saiyi Zhong and Suresh Veeraperumal

Mar. Drugs 2025, 23(4), 163; https://doi.org/10.3390/md23040163 - 8 Apr 2025

Viewed by 500

Abstract

Undaria pinnatifida, an edible brown seaweed that is widely consumed in East Asia, has gained increasing recognition for its health benefits. Among its bioactive compounds, polysaccharides have attracted significant attention due to their diverse biological activity. This review provides a comprehensive overview [...] Read more.

Undaria pinnatifida, an edible brown seaweed that is widely consumed in East Asia, has gained increasing recognition for its health benefits. Among its bioactive compounds, polysaccharides have attracted significant attention due to their diverse biological activity. This review provides a comprehensive overview of recent advancements in the extraction, purification, structural characterization, and bioactivity of U. pinnatifida polysaccharides. We discuss state-of-the-art extraction techniques, including ultrasound-assisted, microwave-assisted, and enzyme-assisted extraction, as well as purification strategies such as membrane separation and chromatographic methods. Furthermore, we highlight their potential biological activity, including antioxidant, immunomodulatory, anticancer, gut health-promoting, and anti-hyperglycemic effects, along with their underlying mechanisms of action. By summarizing the latest research, this review aims to provide valuable insights into the development and application of U. pinnatifida polysaccharides in functional foods and pharmaceuticals. Full article

(This article belongs to the Special Issue Isolation, Identification and Applications of Marine Source Polysaccharides and Peptides—2nd Edition)

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18 pages, 2724 KiB

Open AccessArticle

Identification and Evaluation of Antioxidant and Anti-Aging Peptide Fractions from Enzymatically Hydrolyzed Proteins of Spirulina platensis and Chlorella vulgaris

by Baran Masoumifeshani, Abdolmohammad Abedian Kenari, Ignacio Sottorff, Max Crüsemann and Jamshid Amiri Moghaddam

Mar. Drugs 2025, 23(4), 162; https://doi.org/10.3390/md23040162 - 8 Apr 2025

Viewed by 479

Abstract

Microalgae are a promising source of bioactive compounds, particularly proteins and peptides, with potential applications in skin health and the cosmetic industry. This study investigated the antioxidant and anti-aging properties of peptide fractions derived from Spirulina platensis and Chlorella vulgaris. Both microalgae [...] Read more.

Microalgae are a promising source of bioactive compounds, particularly proteins and peptides, with potential applications in skin health and the cosmetic industry. This study investigated the antioxidant and anti-aging properties of peptide fractions derived from Spirulina platensis and Chlorella vulgaris. Both microalgae were cultivated, and their proteins were subsequently extracted, enzymatically hydrolyzed with alcalase, and fractionated through ultrafiltration. Alkaline extraction yielded 82% protein from S. platensis and 72% from C. vulgaris. Enzymatic hydrolysis predominantly yielded <3 kDa peptides, which exhibited strong antioxidant activity reaching 78% for 2,2-diphenyl-1-picrylhidrazol (DPPH), 82% for 2,2′-azinobis-3-etilbenzothiazoline-6-sulfonic acid (ABTS), and 74% for ferric reducing antioxidant power (FRAP), with IC₅₀ values as low as 23.44 µg/mL for ABTS inhibition in C. vulgaris. These peptides also significantly inhibited skin-aging enzymes, showing 84% inhibition of elastase, 90% of collagenase, and 66% of tyrosinase. Mass spectrometry and GNPS molecular networking of the <3 kDa fraction identified several di- and tri-peptides, including Lys-Val, Val-Arg, His-Ile, Lys-Leu, Ile-Leu, and Leu-Phe, Tyr-Phe, and Leu-Gly-Leu, potentially contributing to these bioactivities. These findings suggest that the enzymatic hydrolysis of S. platensis and C. vulgaris proteins provides a sustainable and natural source of bioactive peptides for antioxidant and anti-aging applications in food, pharmaceutical, and cosmetic industries. Full article

(This article belongs to the Special Issue Marine Algal Biotechnology and Applications)

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19 pages, 5789 KiB

Open AccessArticle

Sustained Release of αO-Conotoxin GeXIVA[1,2] via Hydrogel Microneedle Patch for Chronic Neuropathic Pain Management

by Rongyan He, Mingjuan Li, Weitao Li, Wenqi Li, Shuting Xiao, Qiuyu Cao, Huanbai Wang, Dongting Zhangsun and Sulan Luo

Mar. Drugs 2025, 23(4), 161; https://doi.org/10.3390/md23040161 - 7 Apr 2025

Viewed by 332

Abstract

Chronic neuropathic pain severely impairs quality of life, with current therapies often causing adverse effects. Our research group identified αO-conotoxin GeXIVA[1,2] as a potent analgesic candidate derived from marine cone snails. However, its clinical application is limited by rapid clearance and complex administration. [...] Read more.

Chronic neuropathic pain severely impairs quality of life, with current therapies often causing adverse effects. Our research group identified αO-conotoxin GeXIVA[1,2] as a potent analgesic candidate derived from marine cone snails. However, its clinical application is limited by rapid clearance and complex administration. This study developed a sustained-release hydrogel microneedle patch encapsulating GeXIVA[1,2] to address these challenges. Optimized 4:3 (w/w) polyvinyl alcohol (PVA)–sucrose hydrogel formulation achieved 98.6% structural integrity and controlled swelling (ratio = 1.9 at 48 h). The microneedles demonstrated uniform conical morphology (height: 889 ± 49 µm, base: 381 ± 26 µm) enabling epidermal penetration. In spared nerve injury (SNI) models, a single microneedle patch application increased mechanical paw withdrawal thresholds from 0.056 g to 0.7269 g, maintaining efficacy for 3 days. Chronic constriction injury (CCI) models showed comparable pain relief. Notably, microneedle patch treatment improved locomotor function in SNI mice (total movement: 1518 cm vs. 1126 cm untreated). This hydrogel microneedle patch platform extends GeXIVA[1,2]’s analgesic duration from hours to days through sustained release, while resolving administration challenges through transdermal delivery, expanding the potential applications of GeXIVA[1,2], and demonstrating a promising strategy for the chronic neuropathic pain management. Full article

(This article belongs to the Section Marine Toxins)

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16 pages, 6298 KiB

Open AccessArticle

Optimization and Preparation of Polysaccharide–Protamine Microspheres with Enhanced Hemostatic and Antibacterial Properties for Wound Healing

by Danling Mei, Feifan Cheng, Yifan Li, Suzhen Zhang, Xueqin Zhao and Yanyan Zhao

Mar. Drugs 2025, 23(4), 160; https://doi.org/10.3390/md23040160 - 6 Apr 2025

Viewed by 314

Abstract

This study employs layer-by-layer self-assembly technology to develop novel antibacterial hemostatic microspheres to tackle significant blood loss and related complications resulting from accidents, surgeries, and natural disasters. By measuring the zeta potential and particle size of protamine, carboxymethyl starch (CMS), and hydroxypropyl trimethyl [...] Read more.

This study employs layer-by-layer self-assembly technology to develop novel antibacterial hemostatic microspheres to tackle significant blood loss and related complications resulting from accidents, surgeries, and natural disasters. By measuring the zeta potential and particle size of protamine, carboxymethyl starch (CMS), and hydroxypropyl trimethyl ammonium chloride chitosan (HACC), the optimal assembly conditions were determined. The optimal pH for the monolayer assembly is 3.0, with a CMS concentration of 3 mg/mL and a mass ratio of 1:4 between protamine and CMS, and the assembly process lasts for 2 h. The optimal assembly conditions for the bilayer assembly are a pH of 4.0, an HACC concentration of 1 mg/mL, and a mass ratio of the one-layer assembly to HACC of 1:2. The performance of the assembled microspheres was analyzed via antibacterial and coagulation experiments, revealing excellent antibacterial and coagulation effects, with inhibition rates against Escherichia coli and Bacillus subtilis both exceeding 99%, and a coagulation index of 0%. Additionally, the bilayer assembled microspheres also exhibited strong adsorption capacity and good biocompatibility. In summary, this study provides important scientific evidence for the development of new hemostatic materials, demonstrating significant clinical application potential. Full article

(This article belongs to the Special Issue Marine Polysaccharide-Based Biomaterials)

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15 pages, 5117 KiB

Open AccessArticle

Heterologous Expression and Biochemical Characterization of a New α-Amylase from Nocardiopsis aegyptia HDN19-252 of Antarctic Animal Origin

by Fuhao Liu, Xiangnan Zheng, Wenhui Liao, Xingtao Ren, Chuanteng Ma, Guojian Zhang, Qian Che, Tianjiao Zhu, Wenxue Wang, Tao Zhang, Feng Han and Dehai Li

Mar. Drugs 2025, 23(4), 159; https://doi.org/10.3390/md23040159 - 4 Apr 2025

Viewed by 418

Abstract

α-Amylases, catalyzing starch degradation, serve as vital biocatalysts in industrial and pharmaceutical applications. This study identified a new α-amylase, Alphaz, from Nocardiopsis aegyptia HDN19-252 of Antarctic animal origin, achieving heterologous expression in Escherichia coli. Phylogenetic analysis confirmed its classification into the GH13_5 [...] Read more.

α-Amylases, catalyzing starch degradation, serve as vital biocatalysts in industrial and pharmaceutical applications. This study identified a new α-amylase, Alphaz, from Nocardiopsis aegyptia HDN19-252 of Antarctic animal origin, achieving heterologous expression in Escherichia coli. Phylogenetic analysis confirmed its classification into the GH13_5 subfamily of glycoside hydrolases. Recombinant Alphaz exhibited optimal activity at 40 °C/pH 8.0 while maintaining stability across 0–30 °C and pH 6.6–9.6. Its distinctive halotolerant properties included full activity retention in 0.6 M NaCl and >60% efficiency in salt-free conditions. The enzyme exhibits tolerance to K⁺, Ca²⁺, and Fe³⁺ while demonstrating specific inhibition by Cu²⁺/Zn²⁺. With its heterologously validated functional properties, Alphaz emerges as a programmable enzymatic tool offering advantages in sustained-release formulation quality control, targeted prodrug modification, and precision medicine applications, thereby enabling sustainable biomanufacturing solutions that harmonize process reliability with environmental compatibility. Full article

(This article belongs to the Special Issue Advances of Marine-Derived Enzymes)

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43 pages, 3187 KiB

Open AccessReview

Marine-Derived Bioactive Compounds: A Promising Strategy for Ameliorating Skeletal Muscle Dysfunction in COPD

by Meiling Jiang, Peijun Li, Xiaoyu Han, Linhong Jiang, Lihua Han, Qinglan He, Chen Yang, Zhichao Sun, Yingqi Wang, Yuanyuan Cao, Xiaodan Liu and Weibing Wu

Mar. Drugs 2025, 23(4), 158; https://doi.org/10.3390/md23040158 - 4 Apr 2025

Viewed by 461

Abstract

Chronic obstructive pulmonary disease (COPD) is frequently accompanied by skeletal muscle dysfunction, a critical and severe extrapulmonary complication. This dysfunction contributes to reduced exercise capacity, increased frequency of acute exacerbations, and elevated mortality, serving as an independent risk factor for poor prognosis in [...] Read more.

Chronic obstructive pulmonary disease (COPD) is frequently accompanied by skeletal muscle dysfunction, a critical and severe extrapulmonary complication. This dysfunction contributes to reduced exercise capacity, increased frequency of acute exacerbations, and elevated mortality, serving as an independent risk factor for poor prognosis in COPD patients. Owing to the unique physicochemical conditions of the marine environment, marine-derived bioactive compounds exhibit potent anti-inflammatory and antioxidant properties, demonstrating therapeutic potential for ameliorating COPD skeletal muscle dysfunction. This review summarizes marine-derived bioactive compounds with promising efficacy against skeletal muscle dysfunction in COPD, including polysaccharides, lipids, polyphenols, peptides, and carotenoids. The discussed compounds have shown bioactivities in promoting skeletal muscle health and suppressing muscle atrophy, thereby providing potential strategies for the prevention and treatment of COPD skeletal muscle dysfunction. These findings may expand the therapeutic strategies for managing COPD skeletal muscle dysfunction. Full article

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

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48 pages, 2121 KiB

Open AccessReview

Bioactivity of Marine-Derived Peptides and Proteins: A Review

by Fereidoon Shahidi and Abu Saeid

Mar. Drugs 2025, 23(4), 157; https://doi.org/10.3390/md23040157 - 4 Apr 2025

Viewed by 661

Abstract

The marine environment, covering over 70% of the Earth’s surface, serves as a reservoir of bioactive molecules, including peptides and proteins. Due to the unique and often extreme marine conditions, these molecules exhibit distinctive structural features and diverse functional properties, making them promising [...] Read more.

The marine environment, covering over 70% of the Earth’s surface, serves as a reservoir of bioactive molecules, including peptides and proteins. Due to the unique and often extreme marine conditions, these molecules exhibit distinctive structural features and diverse functional properties, making them promising candidates for therapeutic applications. Marine-derived bioactive peptides, typically consisting of 3 to 40 amino acid residues—though most commonly, 2 to 20—are obtained from parent proteins through chemical or enzymatic hydrolysis, microbial fermentation, or gastrointestinal digestion. Like peptides, protein hydrolysates from collagen, a dominant protein of such materials, play an important role. Peptide bioactivities include antioxidant, antihypertensive, antidiabetic, antimicrobial, anti-inflammatory, anticoagulant, and anti-cancer effects as well as immunoregulatory and wound-healing activities. These peptides exert their effects through mechanisms such as enzyme inhibition, receptor modulation, and free radical scavenging, among others. Fish, algae, mollusks, crustaceans, microbes, invertebrates, and marine by-products such as skin, bones, and viscera are some of the key marine sources of bioactive proteins and peptides. The advancements in the extraction and purification processes, e.g., enzymatic hydrolysis, ultrafiltration, ion-exchange chromatography, high-performance liquid chromatography (HPLC), and molecular docking, facilitate easy identification and purification of such bioactive peptides in greater purity and activity. Despite their colossal potential, their production, scale-up, stability, and bioavailability are yet to be enhanced for industrial applications. Additional work needs to be carried out for optimal extraction processes, to unravel the mechanisms of action, and to discover novel marine sources. This review emphasizes the enormous scope of marine-derived peptides and proteins in the pharmaceutical, nutraceutical, cosmeceutical, and functional food industries, emphasizing their role in health promotion and risk reduction of chronic diseases. Full article

(This article belongs to the Special Issue The Bioactive Potential of Marine-Derived Peptides and Proteins)

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15 pages, 3276 KiB

Open AccessArticle

In Vitro Digestion and Gut Microbiota Fermentation of the Anticancer Marine Drug BG136: Stability and Biotransformation Investigation

by Xintong Li, Shuying Xu, Baiyuan Chen, Pengcheng Gao, Youjing Lv, Qingsen Shang, Guangli Yu and Guoyun Li

Mar. Drugs 2025, 23(4), 156; https://doi.org/10.3390/md23040156 - 3 Apr 2025

Viewed by 376

Abstract

BG136, a β-1,3/1,6-glucan derived from Durvillaea antarctica, is an injectable anticancer drug and has entered Phase II clinical trials. Rational oral formulation design is a pivotal focus for our future drug development research; therefore, elucidating the gastrointestinal fate of BG136 becomes imperative. [...] Read more.

BG136, a β-1,3/1,6-glucan derived from Durvillaea antarctica, is an injectable anticancer drug and has entered Phase II clinical trials. Rational oral formulation design is a pivotal focus for our future drug development research; therefore, elucidating the gastrointestinal fate of BG136 becomes imperative. This study investigated the stability and biotransformation of BG136 via in vitro digestion and gut microbiota fermentation. The results confirmed BG136’s structural integrity, resistance to degradation in a highly acid environment and by gastrointestinal tract enzymes. In contrast, BG136 was degraded by intestinal bacteria into mid-size fragments along with smaller oligosaccharides. Additionally, the biotransformation process notably elevated total short-chain fatty acids (SCFAs) to 38.37 ± 3.29 mM, representing a 59.4% increase versus controls (24.08 ± 2.29 mM), with propionic acid exhibiting the most substantial increase. Meanwhile, the process was accompanied by significant microbial regulation, including an increase in beneficial genera (Lactobacillus, Enterococcus) and a reduction in Lachnoclostridium populations. Overall, these findings systematically map the oral bioavailability challenges and prebiotic potential of BG136, highlighting its microbiota-modulating capacity through species-specific ecological regulation, providing insights into oral drug development for BG136. Full article

(This article belongs to the Special Issue Marine Natural Products and Signaling Pathways, 2nd Edition)

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9 pages, 2006 KiB

Open AccessCommunication

Effect of Nrf2 Activators in Hepatitis B Virus-Infected Cells Under Oxidative Stress

by Junsei Taira, Takuya Kubo, Hiroya Nagano, Ryuji Tsuda, Takayuki Ogi, Kenji Nakashima and Tetsuro Suzuki

Mar. Drugs 2025, 23(4), 155; https://doi.org/10.3390/md23040155 - 3 Apr 2025

Viewed by 266

Abstract

The liver is an active metabolic site that generates high levels of reactive oxygen species (ROS). Oxidative stress has been implicated in the chronicity of hepatitis and hepatitis B virus (HBV) infection. This study aimed to determine the involvement of oxidative stress in [...] Read more.

The liver is an active metabolic site that generates high levels of reactive oxygen species (ROS). Oxidative stress has been implicated in the chronicity of hepatitis and hepatitis B virus (HBV) infection. This study aimed to determine the involvement of oxidative stress in HBV-infected cells and the efficacy of natural Nrf2 activators. The intracellular HBV pregenomic RNA copy number relative to total RNA was measured by RT-PCR, and various protein expressions associated with oxidative stress were analyzed by a Western blot analysis. The results showed that the Nrf2, HO-1, Akt, and Bcl-xL proteins were decreased by the continuous infection, indicating that HBV-positive cells were exposed to oxidative stress. The present study evaluated the anti-HBV infection effects of the Nrf2 activator fucoxanthin (Fx), a marine carotenoid from edible biological resources, including the comparative natural Nrf2 activator pteryxin (Ptx). These Nrf2 activators suppressed the HBV pregenomic RNA production in the HBV-infected cells, thus increasing the expression of the proteins of Nrf2 and HO-1. In the persistently infected cells transfected with the HBV genome, the Bcl-xL and Keap1 proteins, which contribute to suppressing the HBx protein involved in the HBV replication, were overexpressed. In particular, the activity of these protein expressions was marked at low concentrations of Fx. This suggests that natural Nrf2 activators may play a significant role in the HBV infection and could be a valuable source for further development through the functional utilization of food resources. Full article

(This article belongs to the Special Issue Marine-Derived Bioactive Substances and Their Mechanisms of Action)

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14 pages, 268 KiB

Open AccessArticle

Polyunsaturated Fatty Acids Improved Long Term Prognosis by Reducing Oxidative Stress, Inflammation, and Endothelial Dysfunction in Acute Coronary Syndromes

by Alexandru Covaciu, Theodora Benedek, Elena Bobescu, Horatiu Rus, Valentina Benza, Luigi Geo Marceanu, Simona Grigorescu and Christian Gabriel Strempel

Mar. Drugs 2025, 23(4), 154; https://doi.org/10.3390/md23040154 - 1 Apr 2025

Viewed by 367

Abstract

Background: Oxidative stress, inflammation, and endothelial dysfunction are important processes in the progression of atherosclerosis and the occurrence of acute coronary syndromes (ACSs). Omega-3 polyunsaturated fatty acids (Omega-3 PUFAs) are present in marine organisms and have the capacity to reduce all these processes [...] Read more.

Background: Oxidative stress, inflammation, and endothelial dysfunction are important processes in the progression of atherosclerosis and the occurrence of acute coronary syndromes (ACSs). Omega-3 polyunsaturated fatty acids (Omega-3 PUFAs) are present in marine organisms and have the capacity to reduce all these processes and, at the same time, the progression of atherosclerosis and the emergence of ACSs. Aim: To evaluate the role of Omega-3 PUFAs therapy on parameters of oxidative stress, inflammatory syndrome, endothelial dysfunction, and long-term prognosis in acute coronary syndromes. Methods: One thousand one hundred forty patients were admitted to Clinic County Emergency Hospital Brasov with ACS and were enrolled in a prospective study. The study was divided into four groups related to the type of ACS and treatment with Omega-3 PUFAs added to the optimal medical therapy (OMT). The effect of Omega-3 PUFAs therapy associated with the OMT was determined by measuring the dynamics of the following parameters: (a) oxidative stress—total antioxidant status (TAS), oxidated low density lipoprotein cholesterol antibodies (Ab anti-ox-LDL), IgG anti-Myeloperoxidase antibodies (IgG type Ab anti-MPO); (b) inflammatory syndrome—C-reactive protein and fibrinogen; (c) endothelial dysfunction—flow mediated dilation (FMD) and von Willebrand factor (vWf) activity, from baseline to 6 months of follow-up. Clinical events followed at 5 years were cardiovascular and sudden death, Non-ST and ST segment elevation ACS, in stent thrombosis and restenosis, stroke, readmission in hospital for ACS and for heart failure. Results: In ACS groups, treatment with Omega-3 PUFAs added to the OMT significantly decreased the parameters of oxidative stress, inflammatory syndrome, and endothelial dysfunction at 6 months of follow-up. Regarding the clinical events, a significant reduction in the risk of cardiovascular and sudden death and a decreased incidence of Non-ST and ST segment elevation ACS, in-stent restenosis, readmission for ACS and heart failure, was observed in Omega-3 PUFA-treated groups in comparison to control groups. Conclusions: In acute coronary syndromes, therapy with Omega-3 PUFAs added to the OMT resulted in a significant decrease of parameters of oxidative stress, inflammation, and endothelial dysfunction at 6 months and also a significant improvement in the long-term prognosis. Full article

(This article belongs to the Special Issue Fatty Acids from Marine Organisms, 2nd Edition)

18 pages, 11135 KiB

Open AccessArticle

Isolation and Characterization of Photosensitive Hemolytic Toxins from the Mixotrophic Dinoflagellate Akashiwo sanguinea

by Jiling Pan, Ting Fang, Shuang Xie, Ning Xu and Ping Zhong

Mar. Drugs 2025, 23(4), 153; https://doi.org/10.3390/md23040153 - 31 Mar 2025

Viewed by 271

Abstract

The mixotrophic dinoflagellate Akashiwo sanguinea is known to have acute toxic effects on multiple marine organisms, while the composition and chemical properties of its toxins remain unclear. In this study, we established a method for separation and purification of A. sanguinea toxins using chromatographic [...] Read more.

The mixotrophic dinoflagellate Akashiwo sanguinea is known to have acute toxic effects on multiple marine organisms, while the composition and chemical properties of its toxins remain unclear. In this study, we established a method for separation and purification of A. sanguinea toxins using chromatographic techniques. The acetone extract of A. sanguinea exhibited higher hemolytic activity and shorter incubation time compared to methanol and ethyl acetate extracts. Five fractions were obtained by solid-phase extraction (SPE), of which SPE3 (acetone/water ratio 3:2) and SPE4 (acetone/water ratio 4:1) exhibited the highest hemolytic activities and allelopathic effects. Further purification on SPE3 and SPE4 using reverse-phase high-performance liquid chromatography (RP-HPLC) coupled with a diode array detector (DAD) resulted in 11 subfractions, among which Fr4-5 displayed the strongest hemolytic activity. Nearly all active subfractions exhibited higher hemolytic activities incubated under light than those in the dark (p < 0.05), suggesting that A. sanguinea can produce both photosensitive and non-photosensitive toxins, with the former being the primary contributors to its hemolytic activity. Molecular characterization by UV-Vis, FTIR, and HRMS/MS analysis revealed that the structural features of Fr4-5 were highly consistent with porphyrin analogs and could be derived from chlorophyll c-related precursors. These findings highlight that the photosensitive toxins in A. sanguinea may serve dual roles in stress adaptation and ecological competition, potentially contributing to the formation of the blooms. Full article

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

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67 pages, 6303 KiB

Open AccessReview

Bioactive Compounds of Marine Algae and Their Potential Health and Nutraceutical Applications: A Review

by Emin Cadar, Antoanela Popescu, Ana-Maria-Laura Dragan, Ana-Maria Pesterau, Carolina Pascale, Valentina Anuta, Irina Prasacu, Bruno Stefan Velescu, Cezar Laurentiu Tomescu, Claudia Florina Bogdan-Andreescu, Rodica Sirbu and Ana-Maria Ionescu

Mar. Drugs 2025, 23(4), 152; https://doi.org/10.3390/md23040152 - 31 Mar 2025

Viewed by 1253

Abstract

Currently, marine algae are still an under-exploited natural bioresource of bioactive compounds. Seaweeds represent a sustainable source for obtaining bioactive compounds that can be useful for the fabrication of new active products with biomedical benefits and applications as biomedicinals and nutraceuticals. The objective [...] Read more.

Currently, marine algae are still an under-exploited natural bioresource of bioactive compounds. Seaweeds represent a sustainable source for obtaining bioactive compounds that can be useful for the fabrication of new active products with biomedical benefits and applications as biomedicinals and nutraceuticals. The objective of this review is to highlight scientific papers that identify biocompounds from marine macroalgae and emphasize their benefits. The method used was data analysis to systematize information to identify biocompounds and their various benefits in pharmaceuticals, cosmetics, and nutraceuticals. The research results demonstrate the multiple uses of seaweeds. As pharmaceuticals, seaweeds are rich sources of bioactive compounds like polysaccharides, protein compounds, pigments, and polyphenols, which have demonstrated various pharmacological activities such as antioxidant, antibacterial, anti-inflammatory, antiviral, anticoagulant, and potentially anticarcinogenic effects. Seaweed has gained recognition as a functional food and offers a unique set of compounds that promote body health, including vitamins, minerals, and antioxidants. In conclusion, the importance of this review is to expand the possibilities for utilizing natural resources by broadening the areas of research for human health and marine nutraceuticals. Full article

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

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25 pages, 2493 KiB

Open AccessReview

Comprehensive Review on Application Progress of Marine Collagen Cross-Linking Modification in Bone Repairs

by Xiaofei Zhai, Xinrong Geng, Wenjun Li, Hongli Cui, Yunqing Wang and Song Qin

Mar. Drugs 2025, 23(4), 151; https://doi.org/10.3390/md23040151 - 30 Mar 2025

Viewed by 500

Abstract

Bone tissue injuries are a significant health risk, and their repair is challenging. While various materials have potential for bone repair, issues like sourcing and immune rejection limit their use. Marine-derived collagen, abundant and free from religious and disease transmission concerns, is a [...] Read more.

Bone tissue injuries are a significant health risk, and their repair is challenging. While various materials have potential for bone repair, issues like sourcing and immune rejection limit their use. Marine-derived collagen, abundant and free from religious and disease transmission concerns, is a promising biomaterial in bone tissue engineering. Cross-linking modification can enhance its mechanical properties and degradation rate, making it more suitable for bone repair. However, detailed analysis of cross-linking methods, property changes post-cross-linking, and their impact on bone repair is needed. This review examines marine collagen’s modification methods, improved characteristics, and potential in bone tissue repair, providing a foundation for its effective use in bone tissue engineering. Full article

(This article belongs to the Special Issue Collagen and Chitin from Marine Resources and Their Interdisciplinary Applications—2nd Edition)

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17 pages, 3358 KiB

Open AccessArticle

Preparation and Characterization of Polyphenol-Functionalized Chitooligosaccharide Pyridinium Salts with Antioxidant Activity

by Zhen Qi, Wenqiang Tan, Zhanyong Guo and Aili Jiang

Mar. Drugs 2025, 23(4), 150; https://doi.org/10.3390/md23040150 - 30 Mar 2025

Viewed by 316

Abstract

As a kind of eco-friendly material with wide application prospects, chitooligosaccharide (COS) has attracted increasing attention because of its unique bioactivities. In this study, novel polyphenol-functionalized COS pyridinium salts were designed and synthesized. The structural characteristics of the desired derivatives were confirmed by [...] Read more.

As a kind of eco-friendly material with wide application prospects, chitooligosaccharide (COS) has attracted increasing attention because of its unique bioactivities. In this study, novel polyphenol-functionalized COS pyridinium salts were designed and synthesized. The structural characteristics of the desired derivatives were confirmed by FT-IR and ¹H NMR spectroscopy. Their antioxidant activities were evaluated in vitro by DPPH radical scavenging assay, superoxide anion radical scavenging assay, and reducing power assay. The solubility assay in common solvents and cytotoxicity assay against L929 cells using the MTT method in vitro were also performed. The antioxidant assay results showed that the compounds functionalized by polyphenol displayed improved antioxidant activities, which were enhanced with the increase of sample concentration and the number of phenolic hydroxyl groups. The solubility assay indicated that the prepared derivatives had good water solubility. Besides, the modified products were non-toxic to the cells tested. In short, the polyphenol-functionalized COS pyridinium salts with enhanced antioxidant activity and good biocompatibility could be employed as newly safe antioxidant in the fields of biomedicine and food. Full article

(This article belongs to the Section Biomaterials of Marine Origin)

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Mar. Drugs, Volume 23, Issue 4 (April 2025) – 44 articles

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