Contents lists available at ScienceDirect Ecotoxicology and Environmental Safety journal homepage: www.elsevier.com/locate/ecoenv Identification of highly effective antitrypanosomal compounds in essential oils from the Apiaceae family Stephane L. Ngahang Kamte a,1 , Farahnaz Ranjbarian b,1 , Kevin Cianfaglione c,d , Stefania Sut e , Stefano Dall’Acqua e , Maurizio Bruno f , Fariba Heshmati Afshar g , Romilde Iannarelli a , Giovanni Benelli h,i , Loredana Cappellacci a , Anders Hofer b , Filippo Maggi a, ⁎ , Riccardo Petrelli a a School of Pharmacy, University of Camerino, Camerino, Italy b Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden c EA 2219 Géoarchitecture, UFR Sciences & Techniques, Université de Bretagne Occidentale, Brest, France d School of Biosciences and Veterinary Medicine, University of Camerino, Camerino, Italy e Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy f Department STEBICEF, University of Palermo, Viale delle Scienze, Parco d’Orleans II, Palermo, Italy g Department of Pharmacognosy, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran h Department of Agriculture, Food and Environment, University of Pisa, Pisa, Italy i The BioRobotics Institute, Sant’Anna School of Advanced Studies, Pontedera, Pisa, Italy ARTICLE INFO Keywords: Apiaceae Essential oils Human African trypanosomiasis Trypanosoma brucei BALB/3T3 ABSTRACT The Apiaceae family encompasses aromatic plants of economic importance employed in foodstuffs, beverages, perfumery, pharmaceuticals and cosmetics. Apiaceae are rich sources of essential oils because of the wealth of secretory structures (ducts and vittae) they are endowed with. The Apiaceae essential oils are available on an industrial level because of the wide cultivation and disposability of the bulky material from which they are extracted as well as their relatively cheap price. In the fight against protozoal infections, essential oils may represent new therapeutic options. In the present work, we focused on a panel of nine Apiaceae species (Siler montanum, Sison amomum, Echinophora spinosa, Kundmannia sicula, Crithmum maritimum, Helosciadium nodi- florum, Pimpinella anisum, Heracleum sphondylium and Trachyspermum ammi) and their essential oils as a model for the identification of trypanocidal compounds to be used as alternative/integrative therapies in the treatment of Human African trypanosomiasis (HAT) and as starting material for drug design. The evaluation of inhibitory effects of the Apiaceae essential oils against Trypanosoma brucei showed that some of them (E. spinosa, S. amomum, C. maritimum and H. nodiflorum) were active, with EC 50 in the range 2.7–10.7 μg/mL. Most of these oils were selective against T. brucei, except the one from C. maritimum that was highly selective against the BALB/ 3T3 mammalian cells. Testing nine characteristic individual components (α-pinene, sabinene, α-phellandrene, p- cymene, limonene, β-ocimene, γ-terpinene, terpinolene, and myristicin) of these oils, we showed that some of them had much higher selectivity than the oils themselves. Terpinolene was particularly active with an EC 50 value of 0.035 μg/mL (0.26 μM) and a selectivity index (SI) of 180. Four other compounds with EC 50 in the range 1.0–6.0 μg/mL (7.4–44 μM) had also good SI: α-pinene (> 100), β-ocimene (> 91), limonene (> 18) and sa- binene (> 17). In conclusion, these results highlight that the essential oils from the Apiaceae family are a reservoir of substances to be used as leading compounds for the development of natural drugs for the treatment of HAT. 1. Introduction Human African trypanosomiasis (HAT), also known as African sleeping sickness, is a neglected disease endemic in most parts of sub- Saharan Africa, caused by the protozoan Trypanosoma brucei Plimmer & Bradford vectored by infected tsetse flies (Glossina spp., Diptera: Glossinidae) as the main vector. Although HAT incidence is decreasing in the last years, mortality rates are still high in rural and low-income populations that are unable to access appropriate therapies (Steverding, 2010). As a consequence, patients suffering from HAT undergo death in https://doi.org/10.1016/j.ecoenv.2018.03.032 Received 25 November 2017; Received in revised form 1 February 2018; Accepted 8 March 2018 ⁎ Correspondence to: School of Pharmacy, University of Camerino, via S. Agostino 1, 62032 Camerino, Italy. 1 These authors equally contributed to the article. E-mail address: filippo.maggi@unicam.it (F. Maggi). Ecotoxicology and Environmental Safety 156 (2018) 154–165 0147-6513/ © 2018 Elsevier Inc. All rights reserved. T