Pharmacological actions of dieckol on modulation of platelet functions and thrombus formation via integrin αIIbβ3 and cAMP signaling
Background and purpose: Dieckol is a phlorotannin that can be found in seaweeds, particularly in Eisenia bicyclis (brown algae) and is known to have anti-oxidant, anti-inflammatory, and anti-microbial properties. It also possesses anti-thrombotic and pro-fibrinolytic activities; however, the mechani...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-03-01
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| Series: | Pharmacological Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661822000330 |
| _version_ | 1797366701887586304 |
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| author | Muhammad Irfan Tae-Hyung Kwon Hyuk-Woo Kwon Man Hee Rhee |
| author_facet | Muhammad Irfan Tae-Hyung Kwon Hyuk-Woo Kwon Man Hee Rhee |
| author_sort | Muhammad Irfan |
| collection | DOAJ |
| description | Background and purpose: Dieckol is a phlorotannin that can be found in seaweeds, particularly in Eisenia bicyclis (brown algae) and is known to have anti-oxidant, anti-inflammatory, and anti-microbial properties. It also possesses anti-thrombotic and pro-fibrinolytic activities; however, the mechanistic aspects of anti-platelet and anti-thrombotic activity are yet to be explored. Study design and methodology: We investigated the pharmacological effects of dieckol on the modulation of platelet functions using human, rat, and mice models. Inhibitory effects of dieckol on platelet aggregation were assessed using platelet-rich plasma and washed platelets, followed by measurement of dense granule secretions, fibrinogen binding to integrin αIIbβ3, fibronectin adhesion assay, platelet spreading on immobilized fibrinogen, and clot retraction. Cyclic nucleotide signaling events were evaluated, such as cyclic-AMP production followed by vasodilator-stimulated phosphoprotein (VASP) stimulation. The in vivo anti-thrombotic potential was evaluated in mice using an acute pulmonary thromboembolism model and tail bleeding assay. Results: Dieckol markedly inhibited platelet aggregation and granule secretion; furthermore, it down-regulated integrin αIIbβ3–mediated inside-out and outside-in signaling events, including platelet adhesion, spreading, and clot retraction, whereas it upregulated the cAMP–PKA–VASP pathway. Dieckol-treated mice significantly survived the thrombosis than vehicle treated mice, without affecting hemostasis. Histological examinations of lungs revealed minimum occluded vasculature in dieckol-treated mice. Conclusion: Dieckol possesses strong anti-platelet and anti-thrombotic properties and is a potential therapeutic drug candidate to treat and prevent platelet-related cardiovascular disorders. |
| first_indexed | 2024-03-08T17:07:28Z |
| format | Article |
| id | doaj.art-fe016d2a851f49f3a45ea3ab22b8df10 |
| institution | Directory Open Access Journal |
| issn | 1096-1186 |
| language | English |
| last_indexed | 2024-03-08T17:07:28Z |
| publishDate | 2022-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj.art-fe016d2a851f49f3a45ea3ab22b8df102024-01-04T04:36:21ZengElsevierPharmacological Research1096-11862022-03-01177106088Pharmacological actions of dieckol on modulation of platelet functions and thrombus formation via integrin αIIbβ3 and cAMP signalingMuhammad Irfan0Tae-Hyung Kwon1Hyuk-Woo Kwon2Man Hee Rhee3Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea; Department of Oral Biology, College of Dentistry, University of Illinois Chicago, Chicago 60612, IL, USAChuncheon Bio Industry Foundation, Chuncheon 24232, Republic of KoreaDepartment of Biomedical Laboratory Science, Far East University, Eumseong 27601, Republic of KoreaDepartment of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea; Correspondence to: Laboratory of Physiology and Cell Signaling, College of Veterinary Medicine, Kyungpook National University, Daegu 41566, Republic of Korea.Background and purpose: Dieckol is a phlorotannin that can be found in seaweeds, particularly in Eisenia bicyclis (brown algae) and is known to have anti-oxidant, anti-inflammatory, and anti-microbial properties. It also possesses anti-thrombotic and pro-fibrinolytic activities; however, the mechanistic aspects of anti-platelet and anti-thrombotic activity are yet to be explored. Study design and methodology: We investigated the pharmacological effects of dieckol on the modulation of platelet functions using human, rat, and mice models. Inhibitory effects of dieckol on platelet aggregation were assessed using platelet-rich plasma and washed platelets, followed by measurement of dense granule secretions, fibrinogen binding to integrin αIIbβ3, fibronectin adhesion assay, platelet spreading on immobilized fibrinogen, and clot retraction. Cyclic nucleotide signaling events were evaluated, such as cyclic-AMP production followed by vasodilator-stimulated phosphoprotein (VASP) stimulation. The in vivo anti-thrombotic potential was evaluated in mice using an acute pulmonary thromboembolism model and tail bleeding assay. Results: Dieckol markedly inhibited platelet aggregation and granule secretion; furthermore, it down-regulated integrin αIIbβ3–mediated inside-out and outside-in signaling events, including platelet adhesion, spreading, and clot retraction, whereas it upregulated the cAMP–PKA–VASP pathway. Dieckol-treated mice significantly survived the thrombosis than vehicle treated mice, without affecting hemostasis. Histological examinations of lungs revealed minimum occluded vasculature in dieckol-treated mice. Conclusion: Dieckol possesses strong anti-platelet and anti-thrombotic properties and is a potential therapeutic drug candidate to treat and prevent platelet-related cardiovascular disorders.http://www.sciencedirect.com/science/article/pii/S1043661822000330Anti-plateletCyclic-AMPDieckolIntegrin αIIbβ3ThrombosisVASPSer−157 |
| spellingShingle | Muhammad Irfan Tae-Hyung Kwon Hyuk-Woo Kwon Man Hee Rhee Pharmacological actions of dieckol on modulation of platelet functions and thrombus formation via integrin αIIbβ3 and cAMP signaling Pharmacological Research Anti-platelet Cyclic-AMP Dieckol Integrin αIIbβ3 Thrombosis VASPSer−157 |
| title | Pharmacological actions of dieckol on modulation of platelet functions and thrombus formation via integrin αIIbβ3 and cAMP signaling |
| title_full | Pharmacological actions of dieckol on modulation of platelet functions and thrombus formation via integrin αIIbβ3 and cAMP signaling |
| title_fullStr | Pharmacological actions of dieckol on modulation of platelet functions and thrombus formation via integrin αIIbβ3 and cAMP signaling |
| title_full_unstemmed | Pharmacological actions of dieckol on modulation of platelet functions and thrombus formation via integrin αIIbβ3 and cAMP signaling |
| title_short | Pharmacological actions of dieckol on modulation of platelet functions and thrombus formation via integrin αIIbβ3 and cAMP signaling |
| title_sort | pharmacological actions of dieckol on modulation of platelet functions and thrombus formation via integrin αiibβ3 and camp signaling |
| topic | Anti-platelet Cyclic-AMP Dieckol Integrin αIIbβ3 Thrombosis VASPSer−157 |
| url | http://www.sciencedirect.com/science/article/pii/S1043661822000330 |
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