4-Methylcatechol, a Flavonoid Metabolite with Potent Antiplatelet Effects
Language English Country Germany Media electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- Keywords
- 4-methylcatechol, aggregation, flavonoids, metabolites, platelets, pyrogallol,
- 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
- Names of Substances
- 4-methylcatechol MeSH Browser
- Platelet Aggregation Inhibitors MeSH
- Cyclooxygenase Inhibitors MeSH
- Enzyme Inhibitors MeSH
- Catechols MeSH
- Arachidonic Acid MeSH
- Pyrogallol MeSH
- Serotonin MeSH
- Thromboxane-A Synthase 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.
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