Marine Drugs最新文献

{"title":"Large-Scale AI-Based Structure and Activity Prediction Analysis of ShK Domain Peptides from Sea Anemones in the South China Sea.","authors":"Ziqiang Hua, Limin Lin, Wanting Yang, Linlin Ma, Meiling Huang, Bingmiao Gao","doi":"10.3390/md23020085","DOIUrl":"10.3390/md23020085","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11857629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Omega-3 Fatty Acids for the Treatment of Bipolar Disorder Symptoms: A Narrative Review of the Current Clinical Evidence.","authors":"Evmorfia Psara, Sousana K Papadopoulou, Maria Mentzelou, Gavriela Voulgaridou, Theophanis Vorvolakos, Thomas Apostolou, Constantinos Giaginis","doi":"10.3390/md23020084","DOIUrl":"10.3390/md23020084","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11857698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiaging Potential of Lipophilic Extracts of <i>Caulerpa prolifera</i>.","authors":"Gonçalo P Rosa, Maria Carmo Barreto, Ana M L Seca, Diana C G A Pinto","doi":"10.3390/md23020083","DOIUrl":"10.3390/md23020083","url":null,"abstract":"<p><p>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, <i>Caulerpa prolifera</i> (Forsskål) J.V. Lamouroux has emerged as a promising candidate for cosmeceutical applications. This study provides the most comprehensive phytochemical assessment of <i>C. prolifera</i> 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 <i>C. prolifera</i> and its bioactivities, emphasizing its potential as a source of cosmeceutical ingredients, leading to a more comprehensive valorization of this macroalga.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11857742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioprospecting Bioactive Peptides in <i>Halobatrachus didactylus</i> Body Mucus: From In Silico Insights to Essential In Vitro Validation.","authors":"Marta Fernandez Cunha, Ezequiel R Coscueta, María Emilia Brassesco, Frederico Almada, David Gonçalves, Maria Manuela Pintado","doi":"10.3390/md23020082","DOIUrl":"10.3390/md23020082","url":null,"abstract":"<p><p>Fish body mucus plays a protective role, especially in <i>Halobatrachus didactylus</i>, 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 <i>Pseudomonas aeruginosa</i> 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.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11857211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening of Potential Angiotensin-Converting Enzyme-Inhibitory Peptides in Squid (<i>Todarodes pacificus</i>) Skin Hydrolysates: Preliminary Study of Its Mechanism of Inhibition.","authors":"Mingyuan Li, Qianqian Liang, Yurui Zhang, Xin Jiang, Yuan Gu, Xin Song, Xichang Wang, Wenzheng Shi","doi":"10.3390/md23020081","DOIUrl":"10.3390/md23020081","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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⁺.</p><p><strong>Conclusions: </strong>Squid skin constitutes a viable resource for the production of ACEI peptides.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11857160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Marmaricines A-C: Antimicrobial Brominated Pyrrole Alkaloids from the Red Sea Marine Sponge <i>Agelas</i> sp. <i>aff. marmarica</i>.","authors":"Diaa T A Youssef, Areej S Alqarni, Ameen M Almohammadi, Turki Abujamel, Lamiaa A Shaala","doi":"10.3390/md23020080","DOIUrl":"10.3390/md23020080","url":null,"abstract":"<p><p>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 <i>Agelas</i> sp. <i>aff. marmarica</i> 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 (<b>1</b>-<b>3</b>), 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 <i>Staphylococcus aureus</i> (MRSA), <i>Escherichia coli</i>, and <i>Candida albicans</i>. 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 <i>C. albicans</i>, 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 <i>E. coli</i>. The results indicate that marmaricines A-C are selectively active against MRSA, and marmaricines B and C demonstrate potential against <i>C. albicans</i>, making them promising candidates for the development of novel antimicrobial agents targeting resistant pathogens.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11857417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Diversity of the Sea Anemone <i>Actinia fragacea</i>: Comparative Analysis of Nematocyst Venom, Mucus, and Tissue-Specific Profiles.","authors":"Ricardo Alexandre Barroso, Tomás Rodrigues, Alexandre Campos, Daniela Almeida, Francisco A Guardiola, Maria V Turkina, Agostinho Antunes","doi":"10.3390/md23020079","DOIUrl":"10.3390/md23020079","url":null,"abstract":"<p><p>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 <i>Actinia fragacea</i> 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 <i>A. fragacea</i>, offering a critical foundation for exploring novel bioactive compounds and valuable insights into its molecular complexity.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11857728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Geliboluols A-D: Kaurane-Type Diterpenoids from the Marine-Derived Rare Actinomycete <i>Actinomadura geliboluensis</i>.","authors":"Chang-Su Heo, Jong Soon Kang, Jeong-Wook Yang, Min Ah Lee, Hwa-Sun Lee, Chang Hwan Kim, Hee Jae Shin","doi":"10.3390/md23020078","DOIUrl":"10.3390/md23020078","url":null,"abstract":"<p><p>Four new kaurane-type diterpenoids, geliboluols A-D (<b>1</b>-<b>4</b>), along with one known analog (<b>5</b>), were isolated from the culture broth of the marine-derived rare actinomycete <i>Actinomadura geliboluensis</i>. The structures of compounds <b>1</b>-<b>4</b> 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 <b>4</b> 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.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11857663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wound Healing, Antioxidant, and Antiviral Properties of Bioactive Polysaccharides of Microalgae Strains Isolated from Greek Coastal Lagoons.","authors":"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, Emmanouil Flemetakis","doi":"10.3390/md23020077","DOIUrl":"10.3390/md23020077","url":null,"abstract":"<p><p>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 <i>Tetraselmis</i>, <i>Dunaliella,</i> and <i>Nannochloropsis</i>, 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, <i>α</i>- and <i>β</i>-glucans. <i>Tetraselmis verrucosa</i> f. <i>rubens</i> PLA1-2 and <i>T</i>. <i>suecica</i> T3-1 were rich in <i>β</i>-glucans (11%, and 8.1%, respectively). The polysaccharides of the two <i>Tetraselmis</i> 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 <i>T</i>. <i>verrucosa</i> f. <i>rubens</i> PLA1-2 was rich in sulfated polysaccharides, had antioxidant capacity, and exhibited healing properties. The anionic polysaccharides from the two <i>Tetraselmis</i> 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.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11857774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of Transcriptomics and Proteomics to Elucidate Inhibitory Effect and Mechanism of Antifungalmycin B from Marine <i>Streptomyces hiroshimensis</i> in Treating <i>Talaromyces marneffei</i>.","authors":"Qiqi Li, Zhou Wang, Cuiping Jiang, Jianglin Yin, Yonghong Liu, Xinjian Qu, Xiangxi Yi, Chenghai Gao","doi":"10.3390/md23020076","DOIUrl":"10.3390/md23020076","url":null,"abstract":"<p><p><i>Talaromyces marneffei</i> (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 <i>Streptomyces hiroshimensis</i> 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 <i>T. marneffei</i>. In an in vivo mouse model infected with <i>T. marneffei</i> 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 <i>T. marneffei</i>. 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.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11857274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}