The Marine-Derived Triterpenoid Frondoside A Inhibits Thrombus Formation
Background: The marine-derived triterpenoid frondoside A inhibits the phosphatidylinositol-3-kinase (PI3K) pathway in cancer cells. Because this pathway is also crucially involved in platelet activation, we studied the effect of frondoside A on thrombus formation. Methods: Frondoside A effects on pl...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-02-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/18/2/111 |
| _version_ | 1811278932939374592 |
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| author | Emmanuel Ampofo Thomas Später Lisa Nalbach Michael D. Menger Matthias W. Laschke |
| author_facet | Emmanuel Ampofo Thomas Später Lisa Nalbach Michael D. Menger Matthias W. Laschke |
| author_sort | Emmanuel Ampofo |
| collection | DOAJ |
| description | Background: The marine-derived triterpenoid frondoside A inhibits the phosphatidylinositol-3-kinase (PI3K) pathway in cancer cells. Because this pathway is also crucially involved in platelet activation, we studied the effect of frondoside A on thrombus formation. Methods: Frondoside A effects on platelet viability, surface adhesion molecule expression, and intracellular signaling were analyzed by flow cytometry and Western blot. The effect of frondoside A was analyzed by photochemically induced thrombus formation in the mouse dorsal skinfold chamber model and by tail vein bleeding. Results: Concentrations of up to 15 µM frondoside A did not affect the viability of platelets, but reduced their surface expression of P-selectin (CD62P) and the activation of glycoprotein (GP)IIb/IIIa after agonist stimulation. Additional mechanistic analyses revealed that this was mediated by downregulation of PI3K-dependent Akt and extracellular-stimuli-responsive kinase (ERK) phosphorylation. Frondoside A significantly prolonged the complete vessel occlusion time in the mouse dorsal skinfold chamber model of photochemically induced thrombus formation and also the tail vein bleeding time when compared to vehicle-treated controls. Conclusion: Our findings demonstrated that frondoside A inhibits agonist-induced CD62P expression and activation of GPIIb/IIIa. Moreover, frondoside A suppresses thrombus formation. Therefore, this marine-derived triterpenoid may serve as a lead compound for the development of novel antithrombotic drugs. |
| first_indexed | 2024-04-13T00:45:43Z |
| format | Article |
| id | doaj.art-a857090e697f47c092fe2064c6fc7c99 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-13T00:45:43Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-a857090e697f47c092fe2064c6fc7c992022-12-22T03:10:01ZengMDPI AGMarine Drugs1660-33972020-02-0118211110.3390/md18020111md18020111The Marine-Derived Triterpenoid Frondoside A Inhibits Thrombus FormationEmmanuel Ampofo0Thomas Später1Lisa Nalbach2Michael D. Menger3Matthias W. Laschke4Institute for Clinical & Experimental Surgery, Saarland University, 66421 Homburg/Saar, GermanyInstitute for Clinical & Experimental Surgery, Saarland University, 66421 Homburg/Saar, GermanyInstitute for Clinical & Experimental Surgery, Saarland University, 66421 Homburg/Saar, GermanyInstitute for Clinical & Experimental Surgery, Saarland University, 66421 Homburg/Saar, GermanyInstitute for Clinical & Experimental Surgery, Saarland University, 66421 Homburg/Saar, GermanyBackground: The marine-derived triterpenoid frondoside A inhibits the phosphatidylinositol-3-kinase (PI3K) pathway in cancer cells. Because this pathway is also crucially involved in platelet activation, we studied the effect of frondoside A on thrombus formation. Methods: Frondoside A effects on platelet viability, surface adhesion molecule expression, and intracellular signaling were analyzed by flow cytometry and Western blot. The effect of frondoside A was analyzed by photochemically induced thrombus formation in the mouse dorsal skinfold chamber model and by tail vein bleeding. Results: Concentrations of up to 15 µM frondoside A did not affect the viability of platelets, but reduced their surface expression of P-selectin (CD62P) and the activation of glycoprotein (GP)IIb/IIIa after agonist stimulation. Additional mechanistic analyses revealed that this was mediated by downregulation of PI3K-dependent Akt and extracellular-stimuli-responsive kinase (ERK) phosphorylation. Frondoside A significantly prolonged the complete vessel occlusion time in the mouse dorsal skinfold chamber model of photochemically induced thrombus formation and also the tail vein bleeding time when compared to vehicle-treated controls. Conclusion: Our findings demonstrated that frondoside A inhibits agonist-induced CD62P expression and activation of GPIIb/IIIa. Moreover, frondoside A suppresses thrombus formation. Therefore, this marine-derived triterpenoid may serve as a lead compound for the development of novel antithrombotic drugs.https://www.mdpi.com/1660-3397/18/2/111frondoside athrombus formationthrombosishemostasisplateletspi3kdorsal skinfold chamber |
| spellingShingle | Emmanuel Ampofo Thomas Später Lisa Nalbach Michael D. Menger Matthias W. Laschke The Marine-Derived Triterpenoid Frondoside A Inhibits Thrombus Formation Marine Drugs frondoside a thrombus formation thrombosis hemostasis platelets pi3k dorsal skinfold chamber |
| title | The Marine-Derived Triterpenoid Frondoside A Inhibits Thrombus Formation |
| title_full | The Marine-Derived Triterpenoid Frondoside A Inhibits Thrombus Formation |
| title_fullStr | The Marine-Derived Triterpenoid Frondoside A Inhibits Thrombus Formation |
| title_full_unstemmed | The Marine-Derived Triterpenoid Frondoside A Inhibits Thrombus Formation |
| title_short | The Marine-Derived Triterpenoid Frondoside A Inhibits Thrombus Formation |
| title_sort | marine derived triterpenoid frondoside a inhibits thrombus formation |
| topic | frondoside a thrombus formation thrombosis hemostasis platelets pi3k dorsal skinfold chamber |
| url | https://www.mdpi.com/1660-3397/18/2/111 |
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