Coumarin

In nature, coumarin is a widespread substance that is easily soluble in ethanol, ether and essential oils, but not very 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.).

The seeds of the tonka bean are particularly rich in coumarin (the fruits have a coumarin content of around 2 to 3%), as is cinnamon. Coumarin is light-sensitive. Coumarin is produced biosynthetically 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.

Coumarin is found in various plants, such as: the fragrant smoky grass, sweet clover, woodruff, umbelliferous plants such as dill or caraway, dates, the tonka bean (cumaru = tonka bean tree) and cinnamon cassia. Coumarin is a bitter substance due to its bitter taste. The derivatives of 4-hydroxycoumarin are of great medical importance, for example as anticoagulants (see systemic coumarins below); they are also used in pest control.

Coumarin (and related substances) are responsible for the typical hay smell when drying grass or woodruff. Coumarin is partially glycosidically bound in the plant. The substance is only released when the plant is destroyed or when it withers through hydrolytic cleavage of the sugar. Coumarin only then emits its typical odor.

Coumarins are also used in foodstuffs, among other things. In Germany, the limit value for coumarin as a food additive is currently set at 2 mg per kilogram of prepared food in the Flavoring Ordinance.

Coumarin is mainly used as a fragrance and flavoring agent in perfumery and in the tobacco industry. It is also used to flavour drinks and confectionery (including chewing gum), and is also used in the kitchen (in the form of wilted woodruff leaves) to flavour May punch, for example.

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.

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.

Coumarin (and related substances) is responsible, for example, for the typical hay smell when grass is dried. It is found as a flavoring agent in food (e.g. woodruff in punch preparations) and perfumes (sweet, spicy scent reminiscent of fresh hay and woodruff). The coumarin derivatives (see below coumarins, systemic) phenprocoumon and warfarin are anticoagulants.

The daily tolerated dose of an adult should not exceed 50 mg. In homeopathy, there is a negative monograph for coumarin from Commission D.

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.

The starting material for coumarin in the plant is cinnamic acid, from which it is formed by hydroxylation, glycosidation and cyclization. Coumarin is produced synthetically 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 (as antagonists of vitamin K, they inhibit 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.

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