-
Something wrong with this record ?
4-Methylcatechol, a Flavonoid Metabolite with Potent Antiplatelet Effects
L. Applová, J. Karlíčková, P. Warncke, K. Macáková, M. Hrubša, M. Macháček, V. Tvrdý, D. Fischer, P. Mladěnka,
Language English Country Germany
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Platelet Aggregation drug effects MeSH
- Platelet Aggregation Inhibitors pharmacology MeSH
- Cyclooxygenase Inhibitors pharmacology MeSH
- Enzyme Inhibitors pharmacology MeSH
- Catechols pharmacology MeSH
- Chick Embryo MeSH
- Arachidonic Acid pharmacology MeSH
- Humans MeSH
- Drug Evaluation, Preclinical methods MeSH
- Pyrogallol pharmacology MeSH
- Serotonin metabolism MeSH
- Thromboxane-A Synthase antagonists & inhibitors MeSH
- Thrombosis drug therapy MeSH
- Animals MeSH
- Check Tag
- Chick Embryo MeSH
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
SCOPE: Intake of flavonoids from the diet can be substantial, and epidemiological studies suggest that these compounds can decrease the incidence of cardiovascular diseases by involvement with increased platelet aggregation. Although parent flavonoids possess antiplatelet effects, the clinical importance is disputable due to their very low bioavailability. Most of them are metabolized by human colon bacteria to smaller phenolic compounds, which reach higher plasma concentrations than the parent flavonoids. In this study, a series of 29 known flavonoid metabolites is tested for antiplatelet potential. METHODS AND RESULTS: Four compounds appear to have a biologically relevant antiplatelet effect using whole human blood. 4-Methylcatechol (4-MC) is clearly the most efficient being about 10× times more active than clinically used acetylsalicylic acid. This ex vivo effect is also confirmed using a potentially novel in-vivo-like ex ovo hen's egg model of thrombosis, where 4-MC significantly increases the survival of the eggs. The mechanism of action is studied and it seems that it is mainly based on the influence on intracellular calcium signaling. CONCLUSION: This study shows that some flavonoid metabolites formed by human microflora have a strong antiplatelet effect. This information can help to explain the antiplatelet potential of orally given flavonoids.
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc20023750
- 003
- CZ-PrNML
- 005
- 20221018084919.0
- 007
- ta
- 008
- 201125s2019 gw f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1002/mnfr.201900261 $2 doi
- 035 __
- $a (PubMed)31343835
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a gw
- 100 1_
- $a Applová, Lenka $u Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05, Hradec Králové, Czech Republic. $7 xx0277670
- 245 10
- $a 4-Methylcatechol, a Flavonoid Metabolite with Potent Antiplatelet Effects / $c L. Applová, J. Karlíčková, P. Warncke, K. Macáková, M. Hrubša, M. Macháček, V. Tvrdý, D. Fischer, P. Mladěnka,
- 520 9_
- $a SCOPE: Intake of flavonoids from the diet can be substantial, and epidemiological studies suggest that these compounds can decrease the incidence of cardiovascular diseases by involvement with increased platelet aggregation. Although parent flavonoids possess antiplatelet effects, the clinical importance is disputable due to their very low bioavailability. Most of them are metabolized by human colon bacteria to smaller phenolic compounds, which reach higher plasma concentrations than the parent flavonoids. In this study, a series of 29 known flavonoid metabolites is tested for antiplatelet potential. METHODS AND RESULTS: Four compounds appear to have a biologically relevant antiplatelet effect using whole human blood. 4-Methylcatechol (4-MC) is clearly the most efficient being about 10× times more active than clinically used acetylsalicylic acid. This ex vivo effect is also confirmed using a potentially novel in-vivo-like ex ovo hen's egg model of thrombosis, where 4-MC significantly increases the survival of the eggs. The mechanism of action is studied and it seems that it is mainly based on the influence on intracellular calcium signaling. CONCLUSION: This study shows that some flavonoid metabolites formed by human microflora have a strong antiplatelet effect. This information can help to explain the antiplatelet potential of orally given flavonoids.
- 650 _2
- $a zvířata $7 D000818
- 650 _2
- $a kyselina arachidonová $x farmakologie $7 D016718
- 650 _2
- $a katecholy $x farmakologie $7 D002396
- 650 _2
- $a kuřecí embryo $7 D002642
- 650 _2
- $a inhibitory cyklooxygenasy $x farmakologie $7 D016861
- 650 _2
- $a preklinické hodnocení léčiv $x metody $7 D004353
- 650 _2
- $a inhibitory enzymů $x farmakologie $7 D004791
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a agregace trombocytů $x účinky léků $7 D010974
- 650 _2
- $a inhibitory agregace trombocytů $x farmakologie $7 D010975
- 650 _2
- $a pyrogalol $x farmakologie $7 D011748
- 650 _2
- $a serotonin $x metabolismus $7 D012701
- 650 _2
- $a trombóza $x farmakoterapie $7 D013927
- 650 _2
- $a thromboxan-A-synthasa $x antagonisté a inhibitory $7 D013930
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Karlíčková, Jana $u Department of Pharmaceutical Botany, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05, Hradec Králové, Czech Republic.
- 700 1_
- $a Warncke, Paul $u Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmacy, Friedrich-Schiller-University Jena, Lessingstr. 8, 07743, Jena, Germany.
- 700 1_
- $a Macáková, Kateřina $u Department of Pharmaceutical Botany, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05, Hradec Králové, Czech Republic.
- 700 1_
- $a Hrubša, Marcel $u Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05, Hradec Králové, Czech Republic.
- 700 1_
- $a Macháček, Miloslav $u Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05, Hradec Králové, Czech Republic.
- 700 1_
- $a Tvrdý, Václav $u Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05, Hradec Králové, Czech Republic.
- 700 1_
- $a Fischer, Dagmar $u Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmacy, Friedrich-Schiller-University Jena, Lessingstr. 8, 07743, Jena, Germany.
- 700 1_
- $a Mladěnka, Přemysl $u Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05, Hradec Králové, Czech Republic.
- 773 0_
- $w MED00192050 $t Molecular nutrition & food research $x 1613-4133 $g Roč. 63, č. 20 (2019), s. e1900261
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/31343835 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20201125 $b ABA008
- 991 __
- $a 20221018084916 $b ABA008
- 999 __
- $a ok $b bmc $g 1596069 $s 1114426
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2019 $b 63 $c 20 $d e1900261 $e 20190807 $i 1613-4133 $m Molecular nutrition & food research $n Mol Nutr Food Res $x MED00192050
- LZP __
- $a Pubmed-20201125
