{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T01:01:48Z","timestamp":1788483708304,"version":"build-2803163510"},"reference-count":49,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,17]],"date-time":"2025-05-17T00:00:00Z","timestamp":1747440000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF)","award":["2022R1A2C1012963"],"award-info":[{"award-number":["2022R1A2C1012963"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats: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 Fennellia flavipes and evaluated using platelets derived from Sprague\u2013Dawley 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 \u03b1IIb\u03b23-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.<\/jats:p>","DOI":"10.3390\/md23050212","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T05:37:13Z","timestamp":1747633033000},"page":"212","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Dihydrogeodin from Fennellia\u00a0flavipes Modulates Platelet Aggregation via Downregulation of Calcium Signaling, \u03b1IIb\u03b23 Integrins, MAPK, and PI3K\/Akt Pathways"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0244-1945","authenticated-orcid":false,"given":"Abdul Wahab","family":"Akram","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7664-5454","authenticated-orcid":false,"given":"Dae-Cheol","family":"Choi","sequence":"additional","affiliation":[{"name":"Division of Biotechnology and Advanced Institute of Environment and Bioscience, College of Environmental and Bioresource Sciences, Jeonbuk National University, Gobong-ro 79, Iksan 54596, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6876-9460","authenticated-orcid":false,"given":"Hyung-Kyu","family":"Chae","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Dae","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0876-3179","authenticated-orcid":false,"given":"Dongmi","family":"Kwak","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bong-Sik","family":"Yun","sequence":"additional","affiliation":[{"name":"Division of Biotechnology and Advanced Institute of Environment and Bioscience, College of Environmental and Bioresource Sciences, Jeonbuk National University, Gobong-ro 79, Iksan 54596, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3088-1318","authenticated-orcid":false,"given":"Man Hee","family":"Rhee","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea"},{"name":"Institute for Veterinary Biomedical Science, College of Veterinary Medicine Kyungpook National University, Daegu 41566, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lockhart, P.B., and Sun, Y.P. 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