Variability of ferulenol and ferprenin concentration in French giant fennel (Ferula sp.) leaves.

Few studies have reported quantitative data about the levels of prenylated coumarins in Ferula sp. Yet, the toxicity of Ferula sp. is only due to the presence of prenylated coumarins and to their concentrations and all studies suggest the existence of several chemotypes within the same species or even within the same variety. The aim of this study was to investigate the hypothesis of different chemotypes in french Ferula sp. in relationship with the botanical species. In this objective, the species of giant fennels and their concentrations in prenylated coumarins were explored. Three different species or subspecies of giant fennel were detected in continental France: F. communis communis communis L., F. communis catalaunica microcarpa Cauwet-Marc and F. glauca L. Surprisingly, the three species/subspecies of giant fennels were found to be located in exclusive and well separated geographical areas. In French giant fennels, ferulenol and ferprenin were detected. Distribution of ferulenol and ferprenin were found to be different between botanical varieties, but also according to the season, the soil and the altitude. Our study seems to suggest that among F. communis species, the same plant can be regarded as poisonous at one point and another as non-poisonous.

Comparative inhibitory effect of prenylated coumarins, ferulenol and ferprenin, contained in the 'poisonous chemotype' of Ferula communis on mammal liver microsomal VKORC1 activity.

Two distinguishable chemotypes of Ferula communis have been described: the 'nonpoisonous' chemotype, containing as main constituents the daucane esters; and the 'poisonous' chemotype containing prenylated coumarins, such as ferulenol and ferprenin. Ferulenol and ferprenin are 4-oxygenated molecules such as dicoumarol and warfarin, the first developed antivitamin K molecules. Antivitamin K molecules specifically inhibit VKORC1, an enzyme essential for recycling vitamin K. This latest is involved in the activation of clotting factors II, VII, IX, X. The inhibiting effect of ferulenol on VKORC1 was shown in rat, but not for species exposed to F. communis while in vivo studies suggest differences between animal susceptibility to ferulenol. The inhibiting effect of ferprenin on VKORC1 was never demonstrated. The aim of this study was to compare the inhibiting effect of both compounds on VKORC1 of different species exposed to F. communis. Vitamin K epoxide activity was evaluated for each species from liver microsomes and inhibiting effect of ferulenol and ferprenin was characterized. Ferulenol and ferprenin were shown to be able to inhibit VKORC1 from all analyzed species. Nevertheless, susceptibility to ferulenol and ferprenin presented differences between species, suggesting a different susceptibility to 'poisonous' chemotypes of F. communis.