Journal Article Epublish
PubMed: 40422802 DOI: 10.3390/md23050212
Dihydrogeodin from Fennellia flavipes Modulates Platelet Aggregation via Downregulation of Calcium Signaling, αIIbβ 3 Integrins, MAPK, and PI3K/Akt Pathways.
Mar Drugs 23(5)
Authors: Abdul Wahab Akram, Dae-Cheol Choi, Hyung-Kyu Chae, Sung Dae Kim, Dongmi Kwak, Bong-Sik Yun, Man Hee Rhee
Affiliations
- Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea.
- 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.
- Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea. Institute for Veterinary Biomedical Science, College of Veterinary Medicine Kyungpook National University, Daegu 41566, Republic of Korea.
Abstract
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-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 αIIbβ 3-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.
MeSH
Integrins, Pharmaceutical Preparations, Adenosine, Platelet Aggregation, Calcium, Therapeutics, Blood Platelets, Down-Regulation, Calcium Signaling