**2. History**

The medical application of plants containing coumarins probably started long before the isolation of this chemical compound from the Tonka bean in 1820 by Nicholas Jean Baptiste Gaston Guibourt [6]. Ancient Romans produced a cough syrup from the marshmallow (*Althea officinalis*) [7], which contains the coumarin scopoletin [8]. This coumarin demonstrated inhibition of leucocyte migration in mice [9], a process that can be linked to the alleged antitussive effect. Cough is a result of the reaction of the airways to leukotrienes and other factors secreted by leucocytes [10–12]. Inhibition of the migration of these to the affected region consequently reduces the availability of these paracrine factors. In addition, at least one of the herbs mentioned by the famous Roman General Pliny in his pharmacopeia [13] contain coumarins with proven action. For example, the extracts of the common rue or herb-of-grace *Ruta graveolens* contain xanthotoxin [14], a coumarin that reduces the mobility of human spermatozoa possibly through inhibition of membranaeous potassium channels [15].

The application of coumarin and its derivatives in current western medicine dates to the fifties of the past century with the clinical recognition of coumarins as anticoagulant agents. This event was the result of observations of poisoning of animals with coumarin derivatives that led to massive internal organ bleeding [16]. Soon it became clear that the substance that was responsible for the deadly internal bleeding of cattle was dicoumarol [17]. Shortly after this, the proposal was made to develop a coumarin derivative with rodent killing ability and gradually warfarin found its application as a potent rodenticide [18]. When it became clear that this substance also led to bleeding disorders after poisoning in human beings [19], its application as a therapeutic anticoagulant found its way in medicine [20, 21]. Seven decades later, warfarin is still in use as an anticoagulant [22]. In the meantime, several other coumarins with anticoagulant properties like acenocoumarol, phenprocoumon, and fluindione have been developed, and they are used in a variety of clinical settings [23–25].
