Marine Drugs最新文献

{"title":"The Isolation, Structural Characterization, and Biosynthetic Pathway of Unguisin from the Marine-Derived Fungus <i>Aspergillus candidus</i>.","authors":"Wenjiao Diao, Wei Zhang, Xiaoxi Zhang, Siyu Du, Caijuan Zheng, Xuenian Huang, Xuefeng Lu","doi":"10.3390/md23050219","DOIUrl":"10.3390/md23050219","url":null,"abstract":"<p><p>Unguisins, a class of structurally complex cyclic peptides featuring a <i>γ</i>-aminobutyric acid residue embedded in the skeleton, exhibit diverse biological activities. Here, a new unguisin K, along with three known congeners, was isolated from the marine-derived fungus <i>Aspergillus candidus</i> MEFC1001. The biosynthetic pathway was elucidated through gene disruption coupled with in vitro enzymatic characterization. The <i>ugs</i> biosynthetic gene cluster (BGC) containing <i>ugsA</i> and <i>ugsB</i>, in conjunction with an extra-clustered gene <i>ugsC</i>, collaborates to synthesize these unguisins. The alanine racemase (AR) UgsC catalyzes the isomerization of Ala and provides d-Ala as the starter unit for the non-ribosomal peptide synthetase (NRPS). The unique localization of <i>ugsC</i> outside the <i>ugs</i> BGC is different from previously reported unguisin-producing systems where AR genes reside within BGCs. The methyltransferase UgsB mediates a key pre-modification step by methylating phenylpyruvic acid to yield <i>β</i>-methylphenylpyruvate, which is subsequently incorporated as <i>β</i>-methylphenylalanine during NRPS assembly. This represents the first experimental evidence of the <i>β</i>-carbon methylation of Phe residue occurring at the precursor level rather than through post-assembly modification. The NRPS UgsA recruits a variety of amino acids for assembly and cyclization to form mature unguisins. Additionally, genome mining utilizing UgsA as a query identified homologous NRPSs in diverse fungal species, highlighting the potential for unguisin production in fungi. This study enriches the biosynthetic diversity of cyclic peptides and provides guidance for exploring unguisin-like natural products derived from fungi.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 5","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12113358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151029","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":"The Enigma of Sponge-Derived Terpenoid Isothiocyanate-Thiocyanate Pairs: A Biosynthetic Proposal.","authors":"Tadeusz F Molinski","doi":"10.3390/md23050220","DOIUrl":"10.3390/md23050220","url":null,"abstract":"<p><p>The co-occurrence of rare terpenoid thiocyanates (R-SCN), structurally similar to their more common isothiocyanate isomers (R-NCS), poses an enigma: how does the accepted path, terpenyl cation R⁺ → R-NC → R-NCS, accommodate R-SCN? The mystery can now be rationalized by the consideration of three biosynthetic motifs: terpenoid carbocation (R⁺) capture by cyanoformate, NC-COOH (itself in equilibrium with NC^- and CO₂); co-localized rhodanese (a dual-function enzyme) that can both convert fugitive inorganic NC^- to thiocyanate ion, NCS^-, and alkyl isonitriles to alkyl isothiocyanate (R-NC → R-NCS) and adventitious capture of the NCS^- by R⁺. The former two scenarios explain the preponderance of isothiocyanates, R-NCS, as products of a linear reaction path-the α-addition of S⁰ to R-NC-and the third scenario explains minor, less stable thiocyanates, R-SCN, as products of the adventitious capture of liberated NCS^- by the penultimate R⁺ precursor. DFT calculations support this proposal and eliminate other possibilities, e.g., the isomerization of R-NCS to R-SCN.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 5","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12112954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151004","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":"Paralytic Shellfish Toxins in Coastal Waters of Changdao Island (China): Toxin Profiles, Potential Producers, and Environmental Conditions.","authors":"Guanchao Zheng, Yuxiang Deng, Haiyan Wu, Xiaokang Li, Ling Cheng, Chengxu Yuan, Minlu Liu, Zhijun Tan","doi":"10.3390/md23050217","DOIUrl":"10.3390/md23050217","url":null,"abstract":"<p><p>In recent decades, there have been frequent occurrences of paralytic shellfish toxin (PST) contamination in the Yellow and Bohai Seas, China. The waters around Changdao Island, situated at the convergence of these two seas, have suffered harmful algal blooms of <i>Alexandrium</i> spp., indicating a potential risk of PST contamination in shellfish. However, a systematic investigation and assessment of PSTs in this area is still lacking. The presence of PSTs in plankton concentrates and shellfish in coastal areas of Changdao Island was monitored from April to October 2022, using liquid chromatography-tandem mass spectrometry. The potential toxin-producing microalgae were analyzed, as were the environmental conditions associated with their occurrence. The highest levels of PSTs in plankton concentrates and shellfish were both observed in September, reaching levels of 105.8 ng STXeq./L and 114.7 μg STXeq./kg, respectively. The main analogues were C1, C2, and GTX1-4. High-throughput analysis of the plankton concentrates identified eight species of <i>Alexandrium</i>, which are potential producers of PSTs. Sediment samples also revealed the presence of permanent cysts of <i>Alexandrium</i>. This research represents a significant advance in our understanding of the distribution and hypothetical sources of PSTs in the coastal waters of Changdao Island.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 5","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12113264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150989","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":"Bioactivity Assessment and Untargeted Metabolomics of the Mediterranean Sea Pen <i>Pennatula phosphorea</i>.","authors":"Silvia Scarpato, Daniel Venturi, Fortunato Palma Esposito, Maria Cristina Mangano, Gianluca Sarà, Francesco Margiotta, Ester Pagano, Maria Miraglia, Enrico Sangiovanni, Mercedes Garcia-Gil, Lorenzo Di Cesare Mannelli, Carla Ghelardini, Mario Dell'Agli, Angelo A Izzo, Paola Nieri, Donatella de Pascale, Gerardo Della Sala","doi":"10.3390/md23050218","DOIUrl":"10.3390/md23050218","url":null,"abstract":"<p><p>Octocorals have proven to be a prolific source of bioactive natural products, exhibiting a wide spectrum of pharmacological activities. Among octocorals, Pennatulaceans, commonly known as sea pens, are among the most dominant soft coral species living in benthic communities. Nonetheless, reports on bioactivity and chemical investigations of this genus are scarce. This prompted us to shed light on the pharmacological potential of the extracts of the sea pen <i>Pennatula phosphorea</i>, Linneus 1758, and gain an overview of its metabolome. Crude octocoral extracts, obtained with a modified Kupchan extraction protocol, were assessed for their bioactivity potential, revealing the hexanic extract to exert anti-inflammatory effects and interesting protective properties in an in vitro model of sarcopenia and in auditory HEI-OC1 cisplatin-treated cells, while the chloroformic extract was active in reducing A375 melanoma cell viability in a concentration-dependent manner. An untargeted metabolomic analysis unveiled that <i>P. phosphorea</i> collects a wide array of glycerophospholipids and phosphosphingolipids belonging to the ceramide phosphoinositol class, which were exclusive or more abundant in the hexanic extract. Their proven anti-inflammatory and cytoprotective effects could demonstrate the activity shown by the <i>P. phosphorea</i> hexanic extract. In addition, a group of prostaglandins, eluted mainly in the chloroformic extract, were putatively annotated. Since prostanoids from marine origin have been demonstrated to exert cytotoxic and anti-proliferative properties against various cancer cell lines, the presence of PGs in the <i>P. phosphorea</i> chloroform extract could justify its anti-melanoma activity. This is the first report on the presence of glycerophospholipids, phosphosphingolipids, and prostaglandins, along with the identification of novel congeners, in sea pens.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 5","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12113132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150238","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":"<i>Codium fragile</i> Extract Ameliorates Respiratory Function by Controlling Allergic Inflammation in Ovalbumin-Induced Bronchial Disorders in Mice.","authors":"Hyo Lim Lee, Yeong Hyeon Ju, In Young Kim, Hye Ji Choi, Yu Mi Heo, Hwa Rang Na, Ho Jin Heo","doi":"10.3390/md23050221","DOIUrl":"10.3390/md23050221","url":null,"abstract":"<p><p>This study investigated the effect of <i>Codium fragile</i> (WCF) water extract in reducing allergic inflammation in ovalbumin (OVA)-induced mice. Mice were sensitized to OVA + aluminum hydroxide, administered WCF for one week, and exposed to 1% aerosolized OVA. As a result, WCF intake reduced the OVA-induced increase in CD4⁺ T cells, CD8⁺ T cells, the T helper type 2 (Th2)/T helper type 1 (Th1) cell ratio, and inflammatory cells such as eosinophils and lymphocytes. Furthermore, WCF reduced Th2 cytokines such as interleukin (IL)-5, IL-13, and IL-33 and inflammatory cytokines such as tumor necrosis factor α (TNF-α) and IL-1β in lung tissues. A histological analysis showed that WCF intake decreases OVA-induced pulmonary inflammation, bronchial wall thickness, and mucus score and increases pulmonary alveolar area. Moreover, WCF inhibited the nuclear factor κB (NF-κB) pathway, the transforming growth factor β (TGF-β)/Smad pathway, and apoptosis-related proteins in lung tissues that OVA excessively activated. The oleamide (9-octadecenamide) content, representing a physiologically active component of WCF, was analyzed and validated using a high-performance liquid chromatography-photodiode array (HPLC-PDA) system. These results demonstrate that WCF may serve as a potential preventive agent for respiratory dysfunction such as allergic asthma by suppressing NF-κB and TGF-β/Smad pathways.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 5","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12113249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151171","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":"Chartarlactams U-X: Novel Phenylspirodrimanes from a Marine Derived Fungus <i>Stachybotrys</i> sp. SZU-W23 with Anti-Inflammatory Activity Mediated by the NF-κB/ROS Signaling Pathways.","authors":"Yanhua Wu, Lanyi Lu, Peng Zhang, Liyan Wang","doi":"10.3390/md23050216","DOIUrl":"10.3390/md23050216","url":null,"abstract":"<p><p>In this investigation, the anti-inflammatory potential of phenylspirodrimanes (PSDs) produced by the marine-derived fungal strain <i>Stachybotrys</i> sp. SZU-W23 was systematically explored. A total of 15 PSDs were successfully isolated. Among them, four novel compounds, designated as chartarlactams U-X, were precisely characterized using NMR, HRESIMS, and ECD analyses. Specifically, compound <b>10</b> exhibited the most potent inhibitory effect on nitric oxide production in LPS-stimulated RAW 264.7 macrophages within the 0.3-30 μM concentration range, with an IC₅₀ value of 12.4 μM. Additionally, MTT assays revealed no detectable cytotoxicity at these concentrations. Mechanistic studies revealed that compound <b>10</b> effectively suppressed ROS generation, likely inactivating the NF-κB signaling pathway and consequently downregulating pro-inflammatory mediators, including iNOS, IL-6, and IL-1β.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 5","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12113431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150872","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":"Reeler Domain-Containing Proteins Involved in the Antibacterial Immunity of Shrimp <i>Litopenaeus vannamei</i>.","authors":"Jianying Qi, Guoqing Dai, Huiling Xing, Zhibin Fu, Sheng Ke, Lili Shi","doi":"10.3390/md23050215","DOIUrl":"10.3390/md23050215","url":null,"abstract":"<p><p>Like other invertebrates, <i>Litopenaeus vannamei</i> lacks adaptive immunity and relies mainly on innate immunity for defense against foreign pathogens. In this study, three distinct Reeler domain-containing molecules were discovered in <i>L. vannamei</i>, designated as <i>LvReeler1</i>, <i>LvReeler2</i>, and <i>LvReeler3</i>. Analysis of tissue-specific expression patterns indicated that <i>LvReeler1</i> showed predominant expression in the stomach, whereas <i>LvReeler2</i> and <i>LvReeler3</i> demonstrated peak transcriptional activity within gill tissues. The expression of these molecules was induced by <i>Vibrio parahaemolyticus</i>. In vivo interference with <i>LvReelers</i> expressions via dsRNA significantly increased the mortality rate of <i>L. vannamei</i>, while also leading to a marked increase in the bacterial load of <i>V. parahaemolyticus</i> in the gills. Additionally, recombinant proteins of <i>LvReeler1</i> (rLvReeler1), <i>LvReeler2</i> (rLvReeler2), and <i>LvReeler3</i> (rLvReeler3) were successfully expressed in <i>Escherichia coli</i>. Antibacterial assays demonstrated that rLvReelers inhibited the growth of <i>V. parahaemolyticus</i>, <i>Vibrio alginolyticus</i>, and <i>Vibrio harveyi</i>, with rLvReeler3 exhibiting the strongest inhibitory activity. Scanning electron microscopy (SEM) observations revealed that rLvReeler3 caused bacterial aggregates to disintegrate after binding to <i>V. parahaemolyticus</i> and <i>V. alginolyticus</i>. In conclusion, <i>LvReelers</i> play an active role in the antimicrobial immune response of <i>L. vannamei.</i></p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 5","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12113285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150999","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":"Targeting YY1-DR5 Axis by Pyripyropene O as a Novel Therapeutic Strategy Against Prostate Cancer: Molecular Mechanisms and In Vivo Zebrafish Validation.","authors":"Wenxuan Fang, Ying Chen, Mingyi Nie, Xuefeng Zhou, Yonghong Liu, Huaming Tao, Bin Yang, Xueni Wang","doi":"10.3390/md23050214","DOIUrl":"10.3390/md23050214","url":null,"abstract":"<p><strong>Background: </strong>Induction of apoptosis is an important strategy for the treatment of prostate cancer. DR5 is a member of the death receptor superfamily and targeting DR5 is an effective way to induce apoptosis. Pyripyropene O is a natural compound isolated from the marine fungus <i>Aspergillus fumigatus</i> SCSIO 41220. We found it has anti-prostate cancer potential by inducing apoptosis; Methods: The effects of pyripyropene O on the viability, proliferation, cell cycle, apoptosis and migration of prostate cancer cells were investigated by MTT assay, plate clone formation assay, 3D cell sphere assay, flow cytometry and real-time cell analysis. Transmission electron microscopy was used to observe the changes in the internal structure of prostate cancer cells after treatment with pyripyropene O. After determining the mode of cell death, the mechanism of action of pyripyropene O on prostate cancer was further investigated using apoptotic protein microarray, western blot, qPCR, molecular docking, cellular immunofluorescence staining and cellular thermal shift assay. After explaining the mechanism of action of pyriproxyfen O, the in vivo absorption, distribution, metabolism, excretion and potential toxicity of pyriproxyfen O were investigated using ADMETLab 2.0 software. Finally, a zebrafish xenograft tumour model was developed to evaluate the anti-prostate cancer effects of pyriproxyfen O in vivo; Results: The experimental results at the cellular level showed that pyripyropene O inhibited the survival, proliferation and migration of prostate cancer cells, and also showed that pyripyropene O blocked the prostate cancer cell cycle at the G2/M phase and induced apoptosis. At the molecular level, pyripyropene O binds to the transcription factor YY1, promotes YY1 nuclear translocation, regulates the transcription level of DR5, a target gene of YY1, and upregulates the expression of DR5 mRNA and protein. The in vivo results showed that pyripyropene O effectively inhibited the development of prostate cancer in zebrafish; Conclusions: Pyripyropene O has a clear anti-prostate cancer effect at both cellular and animal levels, inhibiting the survival and proliferation of prostate cancer cells by binding to the transcription factor YY1 to activate the expression of DR5 to promote apoptosis, thus exerting an inhibitory effect on prostate cancer.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 5","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12113610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151002","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":"Identification, Expression Profiling, Microbial Binding, and Agglutination Analyses of Two Cathepsin B Genes in Black Rockfish (<i>Sebastes schlegelii</i>).","authors":"Xinghua Zhuang, Xingchun Li, Wenpeng Li, Xuan Xu, Fengjun Lin, Yiying Liu, Chonghui Chen, Xiaoxu Zhang, Pei Zhang, Chao Li, Qiang Fu","doi":"10.3390/md23050213","DOIUrl":"10.3390/md23050213","url":null,"abstract":"<p><p>As a lysosomal cysteine protease of the papain subfamily, cathepsin B (CTSB) is characterized by its innate immune functions and hydrolytic activity. However, the functions of CTSB in the immune responses of teleosts remain to be clarified. In this study, two CTSB genes in <i>S. schlegelii</i>, <i>Ss</i>CTSBa and <i>Ss</i>CTSBb, were identified. Both <i>Ss</i>CTSBa and <i>Ss</i>CTSBb are composed of a 993 bp ORF encoding 330 amino acids. It was found in a phylogeny analysis that both genes form monophyletic clades with their orthologous counterparts of Honeycomb rockfish (<i>Sebastes umbrosus</i>). A synteny analysis indicated that the CTSB homologues were comparatively conserved during vertebrate evolution. Additionally, quantitative real-time PCR revealed the ubiquitous mRNA expression of <i>Ss</i>CTSBa and <i>Ss</i>CTSBb in all of the examined tissues, and substantially differential expression patterns could be observed following <i>Aeromonas salmonicida</i> infection. A subcellular localization analysis demonstrated that the distribution of <i>Ss</i>CTSBa and <i>Ss</i>CTSBb was mainly in the cytoplasm. Moreover, r<i>Ss</i>CTSBa and r<i>Ss</i>CTSBb showed strong binding to Poly(I:C) and exhibited diverse agglutination effects on different bacteria. Overall, these findings suggest that the CTSB genes in black rockfish might show essential functions in the host defense of teleosts against bacterial infections, providing valuable insights for further investigations into the immune mechanism of teleost CTSB.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 5","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12112843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150963","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":"Dihydrogeodin from <i>Fennellia flavipes</i> Modulates Platelet Aggregation via Downregulation of Calcium Signaling, αIIbβ₃ Integrins, MAPK, and PI3K/Akt Pathways.","authors":"Abdul Wahab Akram, Dae-Cheol Choi, Hyung-Kyu Chae, Sung Dae Kim, Dongmi Kwak, Bong-Sik Yun, Man Hee Rhee","doi":"10.3390/md23050212","DOIUrl":"10.3390/md23050212","url":null,"abstract":"<p><p>Cardiovascular disease remains a leading cause of morbidity and mortality worldwide, frequently arising from platelet hyperactivation and subsequent thrombus formation. Although conventional antiplatelet therapies are available, challenges, such as drug resistance and bleeding complications, require the development of novel agents. In this study, dihydrogeodin (DHG) was isolated from <i>Fennellia flavipes</i> and evaluated using platelets derived from Sprague-Dawley rats. Platelet aggregation induced by collagen, adenosine diphosphate, or thrombin was assessed by light transmission aggregometry; DHG significantly reduced aggregation in a dose-dependent manner. Further assays demonstrated that DHG suppressed intracellular calcium mobilization, adenosine triphosphate release, and integrin αIIbβ₃-dependent fibrinogen binding, thereby impairing clot retraction. Western blot analysis revealed that DHG reduced the phosphorylation of mitogen-activated protein kinases (ERK, JNK, p38) and PI3K/Akt, indicating inhibition across multiple platelet-signaling pathways. Additionally, SwissADME-assisted pharmacokinetics predicted favorable properties without violations of the Lipinski (Pfizer) filter, Muegge (Bayer) filter, Ghose filter, Veber filter, and Egan filter, and network pharmacology revealed inhibition of calcium and MAPK pathways. These results highlight the potential of DHG as a novel antiplatelet agent with broad-spectrum activity and promising drug-like characteristics. Further studies are warranted to assess its therapeutic window, safety profile, and potential for synergistic use with existing antiplatelet drugs.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 5","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12112792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150888","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}