Evaluation of safety profile of the essential oils of eight Heracleum taxa (Apiaceae) related to determined furanocoumarin content

Abstract

For essential oils of roots, leaves, flowers and fruits of eight Heracleum taxa (H.sphondylium, H. sibiricum, H. montanum, H. ternatum, H. pyrenaicum subsp. pollinianum, H. pyrenaicum subsp. orsinii, H. verticillatum and H. orphanidis), we previously demonstrated antimicrobial, cytotoxic (selective to cancer cells) and/or antioxidant activities. In this work, for these essential oils maximum daily intake related to total furanocoumarins (FCs) content was estimated, according to Committee on Herbal Medicinal Products of European Medicines Agency (EMA/HMPC) recommendations. FCs were quantified using gas chromatography, and their sum equivalent to xanthotoxin (8-methoxypsoralen, 8-MOP) was calculated. It was shown that daily intake, not contributing significantly to overall risk (equivalent to intake of 1.5 mg FCs) for root essential oils was in the range of 1.94-5.23 mL, for fruit oils of 5.23-15.68 mL and for leaf or flower oils of 2.90-15.68 mL. Daily intake, not posing any unacceptable risk (equivalent to intake of 15 μg FCs) for root oils was in the range of 0.02-0.05 mL, for fruit oils of 0.05-0.16 mL and for leaf or flower oils of 0.03-0.16 mL. This work demonstrates the application of current EMA/HMPC recommendations, in order to establish safety profile of herbal preparations containing FCs.

Za etarska ulja korena, listova, cvasti i plodova osam taksona roda Heracleum (H. sphondylium, H. sibiricum, H. montanum, H. ternatum, H. pyrenaicum subsp. pollinianum, H. pyrenaicum subsp. orsinii, H. verticillatum i H. orphanidis) prethodno su pokazane antimikrobna, citotoksična (selektivna prema tumorskim ćelijama) i/ili antioksidantna aktivnost. Cilj ovog rada bio je da se ustanovi maksimalni dozvoljeni dnevni unos etarskih ulja u odnosu na utvrđeni sadržaj ukupnih furanokumarina, u skladu sa preporukama Komiteta za biljne lekovite proizvode Evropske agencije za lekove (EMA/HMPC). Furanokumarini su kvantifikovani gasnom hromatografijom i njihov ukupni sadržaj izražen je kao ksantotoksin (8- metoksipsoralen, 8-MOP). Dnevni unos ispitivanih etarskih ulja koji ne doprinosi značajno ukupnom riziku (ekvivalentan unosu 1,5 mg furanokumarina izraženih kao 8-MOP), kreće se u opsegu 1,94-5,23 mL za etarska ulja korena, 5,23-15,68 mL za ulja plodova i 2,90-15,68 mL za ulja listova ili cvasti. Dnevni unos etarskih ulja koji ne predstavlja nikakav rizik (ekvivalentan unosu 15 μg furanokumarina izraženih kao 8-MOP), kreće se u opsegu 0,02-0,05 mL za etarska ulja korena, 0,05-0,16 mL za ulja plodova i 0,03-0,16 mL za ulja listova ili cvasti. Ovaj rad demonstrira primenu aktuelnih EMA/HMPC preporuka u cilju utvrđivanja bezbednosnog profila biljnih preparata u kojima su detektovani furanokumarini.