Influence of flavonoids’ lipophilicity on platelet aggregation
Flavonoids are natural polyphenolic compounds present in a wide spectrum of plants that have a beneficial effect on human health. In the context of cardiovascular diseases related to plaque and thrombus formation, flavonoids exhibit an anti-aggregatory effect. Previously, it has been reported that a...
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| Format: | Article |
| Language: | English |
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Sciendo
2019-12-01
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| Series: | Acta Pharmaceutica |
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| Online Access: | https://doi.org/10.2478/acph-2019-0040 |
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| author | Babić Ivana Bojić Mirza Maleš Željan Zadro Renata Gojčeta Koraljka Duka Ivan Rimac Hrvoje Jukić Irena |
| author_facet | Babić Ivana Bojić Mirza Maleš Željan Zadro Renata Gojčeta Koraljka Duka Ivan Rimac Hrvoje Jukić Irena |
| author_sort | Babić Ivana |
| collection | DOAJ |
| description | Flavonoids are natural polyphenolic compounds present in a wide spectrum of plants that have a beneficial effect on human health. In the context of cardiovascular diseases related to plaque and thrombus formation, flavonoids exhibit an anti-aggregatory effect. Previously, it has been reported that all tested flavonoids exhibit an antiaggregatory effect on platelet aggregation when measured by impedance aggregometry on whole blood, in the test of aggregation induced by adenosine diphosphate (ADP). As not all flavonoids have the same targets within signaling pathways, an assumption of a common non-specific mechanism related to lipophilicity is to be considered. To test this hypothesis, reverse-phase thin layer chromatography was used to assess the lipophilicity of flavonoids; impedance aggregometry was used for testing of platelet aggregation and flow cytometry to monitor the influence of flavonoids on platelet activation. Lipophilicity analysis showed a highly negative correlation of logP and MINaAC for groups of flavones and flavanones. As determined by flow cytometry, the exposition of receptors necessary for the promotion of platelet activation and primary clot formation was diminished, i.e., lowered expression of the activated form of integrin αIIbβ3 was observed in the presence of flavanone. Platelet membrane stabilization by flavonoids as a mechanism of antiaggregatory effect has been supported by impedance aggregometry experiments when specific inhibitors of platelet aggregation signaling pathways (U73122, indomethacin, verapamil) were used in the presence of a weak (ADP) and a strong (TRAP-6) agonist of aggregation. While individual flavonoids can have specific targets within aggregation signaling pathways, all flavonoids share a common non-specific mechanism of platelet aggregation inhibition related to their lipophilicity and membrane stabilization that, to some extent, contributes to their antiaggregatory effect. |
| format | Article |
| id | doaj-art-1a4c97dea8a947b293f0c734f7ea61e6 |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2019-12-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Pharmaceutica |
| spelling | doaj-art-1a4c97dea8a947b293f0c734f7ea61e62025-02-02T10:03:15ZengSciendoActa Pharmaceutica1846-95582019-12-0169460761910.2478/acph-2019-0040acph-2019-0040Influence of flavonoids’ lipophilicity on platelet aggregationBabić Ivana0Bojić Mirza1Maleš Željan2Zadro Renata3Gojčeta Koraljka4Duka Ivan5Rimac Hrvoje6Jukić Irena7Croatian Institute of Transfusion Medicine, HR-10000Zagreb, CroatiaUniversity of Zagreb, Faculty of Pharmacy and Biochemistry Department of Medicinal ChemistryHR-10000Zagreb, CroatiaUniversity of Zagreb, Faculty of Pharmacy and Biochemistry Department of Pharmaceutical BotanyHR-10000Zagreb, CroatiaUniversity of Zagreb, Faculty of Pharmacy and Biochemistry Department of Clinical Chemistry and Haematology, HR-10000ZagrebCroatiaCroatian Institute of Transfusion Medicine, HR-10000Zagreb, CroatiaUniversity of Zagreb, Faculty of Pharmacy and Biochemistry Department of Pharmaceutical BotanyHR-10000Zagreb, CroatiaUniversity of Zagreb, Faculty of Pharmacy and Biochemistry Department of Medicinal ChemistryHR-10000Zagreb, CroatiaCroatian Institute of Transfusion Medicine, HR-10000Zagreb, CroatiaFlavonoids are natural polyphenolic compounds present in a wide spectrum of plants that have a beneficial effect on human health. In the context of cardiovascular diseases related to plaque and thrombus formation, flavonoids exhibit an anti-aggregatory effect. Previously, it has been reported that all tested flavonoids exhibit an antiaggregatory effect on platelet aggregation when measured by impedance aggregometry on whole blood, in the test of aggregation induced by adenosine diphosphate (ADP). As not all flavonoids have the same targets within signaling pathways, an assumption of a common non-specific mechanism related to lipophilicity is to be considered. To test this hypothesis, reverse-phase thin layer chromatography was used to assess the lipophilicity of flavonoids; impedance aggregometry was used for testing of platelet aggregation and flow cytometry to monitor the influence of flavonoids on platelet activation. Lipophilicity analysis showed a highly negative correlation of logP and MINaAC for groups of flavones and flavanones. As determined by flow cytometry, the exposition of receptors necessary for the promotion of platelet activation and primary clot formation was diminished, i.e., lowered expression of the activated form of integrin αIIbβ3 was observed in the presence of flavanone. Platelet membrane stabilization by flavonoids as a mechanism of antiaggregatory effect has been supported by impedance aggregometry experiments when specific inhibitors of platelet aggregation signaling pathways (U73122, indomethacin, verapamil) were used in the presence of a weak (ADP) and a strong (TRAP-6) agonist of aggregation. While individual flavonoids can have specific targets within aggregation signaling pathways, all flavonoids share a common non-specific mechanism of platelet aggregation inhibition related to their lipophilicity and membrane stabilization that, to some extent, contributes to their antiaggregatory effect.https://doi.org/10.2478/acph-2019-0040flavonoidsplateletslipophilicityflow cyto metryantiaggregatory activity |
| spellingShingle | Babić Ivana Bojić Mirza Maleš Željan Zadro Renata Gojčeta Koraljka Duka Ivan Rimac Hrvoje Jukić Irena Influence of flavonoids’ lipophilicity on platelet aggregation Acta Pharmaceutica flavonoids platelets lipophilicity flow cyto metry antiaggregatory activity |
| title | Influence of flavonoids’ lipophilicity on platelet aggregation |
| title_full | Influence of flavonoids’ lipophilicity on platelet aggregation |
| title_fullStr | Influence of flavonoids’ lipophilicity on platelet aggregation |
| title_full_unstemmed | Influence of flavonoids’ lipophilicity on platelet aggregation |
| title_short | Influence of flavonoids’ lipophilicity on platelet aggregation |
| title_sort | influence of flavonoids lipophilicity on platelet aggregation |
| topic | flavonoids platelets lipophilicity flow cyto metry antiaggregatory activity |
| url | https://doi.org/10.2478/acph-2019-0040 |
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