Coumarine and coumarin in herbal medicine

See also: coumarin in cosmetics

Coumarins are a family of natural substances widely distributed in the plant world. From the chemical point of view, these are derivatives of 5, 6-benzo-2-pyrone, better known as coumarin.

The term coumarin derives from Coumarona odorata, a South American legume from which the molecule was first isolated in 1820.

In the plant world the coumarins can be found both in free form and in glycosidic form, that is they are bound as aglycone to a sugar part. The great structural heterogeneity of these substances reflects an equally wide pharmacological-therapeutic variability.

Cumarine with phlebotonic action

The phlebotonic adjective belongs to all substances capable of increasing venous tone. The esculin - coumarin glycoside present in the leaves of the horse chestnut (aglycone esculetin) - decreases the permeability of the capillaries (anti-edema action) and increases its resistance, improving the functionality of the vascular pathways also thanks to anti-inflammatory virtues. The same coumarin, which abounds in the flowering tops of the Meliloto (sweet clover), has shown marked anti-edematous properties in animal models; not by chance this drug is suggested, in association with flavonoids, in the treatment and prophylaxis of venous insufficiency and its manifestations.

Coumarins with anticoagulant action

When at the end of the nineteenth century the farmers of North America introduced the odorous clover (meliloto) in their pastures and in the feeding of the cattle, a haemorrhagic epidemic appeared very soon, that only a few years later it turned out to be linked to the use of this new fodder.

In fact, during the drying of the clover, the coumarin undergoes a series of chemical transformations - partly spontaneous and partly mediated by fungi of the Aspergillus genus - which ultimately give rise to dicumarol. This substance interferes with the blood coagulation process, blocking vitamin K synthesis dependent on certain coagulation factors. One of its derivatives, warfarin, is currently used as an oral anticoagulant in the therapy of deep vein thrombosis and as a prophylaxis of pulmonary embolism and cardiac infarction in patients with atrial fibrillation or carriers of artificial heart valves. The same goes for another coumarin derivative, acenocoumarol, the active ingredient of Sintrom with a similar use profile.

Cumarine with spasmolytic action

An example of vegetable substances with hypotensive and spasmolytic properties - capable therefore of inhibiting the spastic contraction of the gastro-enteric and genito-urinary smooth muscles associated with cramp-like or colic-type pain - is given by the coumarins of Viburnum prunifolium (scopoletine) and of the Angelica ('essential oil extracted from the roots).

The coumarins of the Visnaga (kelina or visnadina) concentrate their spasmolytic action at the level of the smooth muscle of the coronary vessels; not by chance this plant is known for its anti-anginal properties.

Coumarine with antibacterial and antiviral action

The umbelliferone present in the aerial parts of the Pilosella and in the resins of many Umbelliferae - in addition to being used as a sun screen - has shown interesting antibiotic properties, especially with regard to Brucella, the etiological agent of Brucellosis. The aforementioned esculetin, on the other hand, exhibits bacteriostatic and antifungal properties, while daphnoretin and 3-phenylcumarins have shown anti-hepatitis B and anti-HIV properties respectively.

Coumarine with anti-inflammatory action

Melilotum coumarin promotes tissue healing and regeneration, thanks to its anti-edema, capillarotropic and erythrocyte membrane stabilizing properties (it counteracts the increase in vascular permeability, a very important element in inflammatory phenomena). The esculetin, on the other hand, inhibits the synthesis of prostanoids (prostaglandins, thromboxanes and leukotrienes), molecules involved in asthmatic, allergic and inflammatory reactions.

Cumarine with photosensitizing action

Two coumarins typical of Bergamot, bergaptene and psoralen, and more generally the other 6, 7-furan-coumarins such as xanthoxin, possess a marked photosensitizing action (they enhance the cutaneous action of ultraviolet rays, in particular those responsible for tanning) ). They are therefore used in so-called photodynamic therapy, used to stimulate skin pigmentation in vitiligo and to a lesser extent in psoriasis and alopecia areata. This practice consists of administering orally or topically applying photosensitizing coumarin preparations, followed by exposure to UVA radiation (320-400 nm).

Side effects of coumarins

Particular caution should be taken in the use of dried coumarin-based herbs, due to the already mentioned ability to produce dicumarol in particular situations (see fermentation of the Melilotus). For obvious reasons, these preparations are absolutely contraindicated in patients on anticoagulant (coumadin, sintrom) or anti-platelet therapy (aspirin, clopidogrel etc.). It must be said, however, that coumarin and the other coumarins in themselves do not possess any notable anticoagulant activity, so on a phytotherapeutic level they should not be confused with dicumarol and its therapeutic applications. Devil's claw, boldo, fenugreek and Chinese angelica are examples of coumarin drugs for which important episodes of drug interaction have been reported, with an increase in the anticoagulant activity of drugs such as warfarin.

High doses of bergaptene - coumarin characteristic of bergamot essential oil and citrus fruits in general - are mutagenic and carcinogenic; moreover, they seem to be responsible for the inhibitory activity on the cytochrome P450 CYP3A4 isoform, characteristic of grapefruit juice (which for this reduces the metabolism of many drugs, increasing their therapeutic activity with the risk of side effects from overdose). Due to their photosensitizing properties, 6, 7-furan-coumarins are contraindicated in case of prolonged exposure to sunlight, due to the risk of photo-dermatitis, burns and melanomas.

Among the coumarin derivatives, the aflatoxins produced by the molds of the genus Aspergillus starting from the coumarins, play a very important toxicological role, because they significantly increase the risk of primitive liver cancer. Coumarin itself is moderately toxic to the liver and kidneys.

Finally, due to their potential toxicity, coumarins are contraindicated during pregnancy and lactation.