Identification of Highly Effective Antitrypanosomal Compounds in Essential Oils From the Apiaceae Family

Ecotoxicol Environ Saf. 2018 Jul 30;156:154-165. doi: 10.1016/j.ecoenv.2018.03.032. Epub 2018 Mar 20.

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 nodiflorum, 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 EC50 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 EC50 value of 0.035 μg/mL (0.26 µM) and a selectivity index (SI) of 180. Four other compounds with EC50 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 sabinene (>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.

Keywords: Apiaceae; BALB/3T3; Essential oils; Human African trypanosomiasis; Trypanosoma brucei.

MeSH terms

  • 3T3 Cells
  • Acyclic Monoterpenes
  • Alkenes / pharmacology
  • Animals
  • Apiaceae / chemistry*
  • Benzyl Compounds / pharmacology
  • Bicyclic Monoterpenes
  • Cyclohexane Monoterpenes
  • Cyclohexenes / pharmacology
  • Cymenes
  • Dioxolanes / pharmacology
  • Inhibitory Concentration 50
  • Limonene
  • Mice
  • Monoterpenes / pharmacology
  • Oils, Volatile / pharmacology*
  • Plant Oils / pharmacology*
  • Pyrogallol / analogs & derivatives
  • Pyrogallol / pharmacology
  • Terpenes / pharmacology
  • Trypanosoma brucei brucei / drug effects*
  • Trypanosomiasis / drug therapy

Substances

  • Acyclic Monoterpenes
  • Alkenes
  • Benzyl Compounds
  • Bicyclic Monoterpenes
  • Cyclohexane Monoterpenes
  • Cyclohexenes
  • Cymenes
  • Dioxolanes
  • Monoterpenes
  • Oils, Volatile
  • Plant Oils
  • Terpenes
  • Pyrogallol
  • myristicin
  • beta-ocimene
  • 4-cymene
  • alpha phellandrene
  • gamma-terpinene
  • sabinene
  • Limonene
  • alpha-pinene
  • terpinolene