Abstract
Marine halophytes are an outstanding reservoir of natural products and several species have anti-infectious traditional uses. However, reports about their potential use against neglected tropical ailments, such as Chagas disease, are scarce. This work evaluated for the first time the in vitro anti-Trypanosoma cruzi activity of extracts from the aromatic and medicinal species Helichrysum italicum subsp. picardii (Boiss. & Reut.) Franco (Asteraceae, everlasting) and Crithmum maritimum L. (Apiaceae, sea fennel). For that purpose, decoctions, tinctures, and essential oils from everlasting’s flowers and sea fennel’s stems, leaves, and flowers were tested against intracellular amastigotes of two T. cruzi strains. The extract from the sea fennel flower decoction displayed significant anti-trypanosomal activity and no toxicity towards the host cell (EC50 = 17.7 µg/mL, selectivity index > 5.65). Subsequent fractionation of this extract afforded 5 fractions that were re-tested in the same model of anti-parasitic activity. Fraction 1 was the most active and selective (EC50 = 0.47 μg/mL, selectivity index = 59.6) and was submitted to preparative thin-layer chromatography. One major compound was identified, falcarindiol, which was likely the one responsible for the observed anti-trypanosomal activity. This was confirmed using a commercially sourced molecule. Target-fishing studies showed falcarindiol as a ligand of T. cruzi spermidine synthase, pointing to a potential enzyme-inhibiting anti-trypanosomal mechanism of action. Overall, this work shows that sea fennel can provide effective anti-parasitic molecule(s) with potential pharmacological applications in the treatment of CD.
Highlights
Neglected tropical diseases (NTDs) are a group of disabling and chronic infections that flourish primarily in impoverished environments impairing the lives of over one billion people worldwide [1,2]
Culture media were purchased from Welgene, Inc. (Seoul, South Korea), fetal bovine serum (FBS) and penicillin/streptomycin from Gibco Inc. (Life Technologies, Billings, MT, USA), DRAQ5TM from BioStatus Ltd
Dried biomass was extracted with water and 80% aqueous ethanol while fresh biomass was used to extract essential oils (EOs), resulting in higher yields (Table 1)
Summary
Neglected tropical diseases (NTDs) are a group of disabling and chronic infections that flourish primarily in impoverished environments impairing the lives of over one billion people worldwide [1,2]. Only two anti-parasitic drugs are approved for CD treatment, namely nifurtimox and benznidazole, and their efficacy, high at the acute stage onset, is low in the chronic phase They are rather toxic, showing several side effects, and require prolonged administration [3,4,6,7,8,9]. A specialized group of plants able to thrive in saline environments, have evolved several adaptations in response to the osmotic and ionic challenges of living in such harsh conditions, including the synthesis of highly bioactive metabolites They represent an outstanding reservoir of natural compounds with some species being used in folk medicine as anti-parasitic and anti-helminthic [10]. Preparative thin-layer chromatography (TLC) followed by nuclear magnetic resonance (NMR) analysis was used to identify the major compound likely responsible for the anti-trypanosomal activity and target fishing studies were performed to uncover probable mechanisms of action
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