DefinitionThis section has been translated automatically.
Coumarin is a widespread substance in nature, readily soluble in ethanol, ether and essential oils, but little soluble in water (coumarin from the Spanish "cumarú = tonka bean tree", a tree native to Guyana (Coumaruona odorata)), which causes the aromatic scent of numerous plants (e.g. woodruff, sweet clover, dates, etc.).
Especially rich in coumarin are the seeds of the tonka bean (the fruits have a coumarin content of about 2 to 3%) as well as cinnamon. Coumarin is sensitive to light. Biosynthetically, coumarin is produced from coumaric acid or its glucoside(melilotoside).
Coumarin was first isolated in 1813 by the German chemist A. Vogel, who was able to extract the substance from the seeds of the tonka tree.
OccurrenceThis section has been translated automatically.
Coumarin can be found in various plants such as: the fragrant perfumed grass, clover, woodruff, umbellifers such as dill or caraway, dates, tonka bean (cumaru = tonka bean tree) and cinnamon cassava. Due to its bitter taste, coumarin belongs to the bitter substances. The derivatives of 4-hydroxycumarin are of great medical importance, for example as anticoagulants (see coumarins systemic); they are also used in pest control.
Coumarin (and related substances) are responsible for the typical hay smell when drying grass or woodruff. In the plant coumarin is partially glycosidically bound. The substance is only released when the plant is destroyed or when it withers by hydrolytic splitting of the sugar. Only then does coumarin exude its typical smell.
Coumarins are also used in food. In Germany, the limit value for coumarin as a food additive is laid down in the Flavour Regulation at currently 2 mg per kilogram of prepared food.
Coumarin is mainly used as a fragrance and flavour in perfumery and in the tobacco industry. Furthermore, it is used to flavour drinks and confectionery (also in chewing gum), e.g. it is also used (in the form of wilted woodruff leaves) in the kitchen, e.g. to flavour May punch.
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EffectsThis section has been translated automatically.
Lymphokinetic, antiphlogistic, antiexudative, anti-edematous, vasodilatory, bronchospasmolytic, cytostatic. The drug has anti-inflammatory, antispasmodic and sedative effects. In the hay flower, where the fine parts of the hay are processed, the effluent coumarin is used as a traditional remedy.
Coumarin, for example in the form of fragrant Mariengras, has a repellent effect on insects.
Elimination and metabolismThis section has been translated automatically.
In humans, coumarin is almost completely absorbed from the gastrointestinal tract after oral administration, but is subject to a pronounced first-pass metabolism in the liver, so that only about 2 to 6 % of the absorbed dose enters the systemic circulation. Under catalysis of CYP2A6, coumarin is predominantly metabolised to 7-hydroxycoumarin, which is excreted renally after conjugation with glucuronide or sulphate.
In animals, coumarin is metabolised in a different way. In rats, mice or dogs, for example, the formation of the hepatotoxic coumarin 3,4-epoxide is predominant.
Field of application/useThis section has been translated automatically.
DosageThis section has been translated automatically.
Ingested perorally in larger amounts, coumarin causes severe headache, vomiting, dizziness and somnolence. In addition, liver and kidney damage is observed in animal studies (depending on the animal species).
The BfR points out that exceedances of the TDI value are only possible if large quantities of, for example, cinnamon spices are consumed. During the Christmas season, this is possible if cassia cinnamon is used in large quantities for baking. For May punch made from woodruff, a maximum of 3 g of herb per liter of punch should be used. In this small amount, the coumarin contained is not harmful to health.
Note(s)This section has been translated automatically.
The starting material for coumarin in the plant is cinnamic acid, from which it is formed by hydroxylation, glycosidation and cyclization. Synthetically, coumarin is produced from salicylaldehyde and acetic anhydride. While coumarin itself has no anticoagulant properties, improper silo storage of hay can lead to fungal infestation of grasses containing coumarin, resulting in the formation of coumarin derivatives (bis-hydroxycoumarins). Bis-hydroxycoumarins have an anticoagulant effect (they act as antagonists of vitamin K, inhibiting the synthesis of the blood coagulation factors II, VII, IX, X formed in the liver). Feeding such hay can lead to the death of the animals.
LiteratureThis section has been translated automatically.
- Allen EV et al (1947) The use of dicumarol as an anticoagulant; experience in 2,307 cases. Ann Intern Med 27:371-381
- Beamand J A. (1998) Lack of effect of coumarin on unscheduled DNA synthesis in precision-cut human liver slices. Food Chem. Toxicol. 36:647-653.
- BGA (1994) Liver toxic effects of coumarins. Drug information of the BGA Pharm In. 56; IV/92.
- Booth NL et al (2004) Confusion regarding anticoagulant coumarins in dietary supplements. Clin. Pharmacol. Ther. 76:511-516.
- Lake BG et al (1996) Use of precision-cut liver slices to evaluate species differences in 2-actylaminofluorene induced unscheduled DNA synthesis. Tox. Appl. Pharm. 138:231-241.
- Ritschel W.A. et al. (1979) First -pass effect of coumarin. Int. J. Clin. Pharmacol. Biopharm. 17:9-103.
- Vassallo JD et al (2004) Metabolic detoxication determines species differences in coumarin induced hapototoxixity. Toxicological Science 80: 249-257