Antischistosomal activity of the terpene nerolidol

Abstract

Schistosomiasis is a neglected tropical disease that affects hundreds of millions of people worldwide. Since the treatment of this disease currently relies on a single drug, praziquantel, new and safe schistosomicidal agents are urgently required. Nerolidol, a sesquiterpene present in the essential oils of several plants, is found in many foods and was approved by the U.S. Food and Drug Administration. In this study we analysed the in vitro antiparasitic effect of nerolidol on Schistosoma mansoni adult worms. Nerolidol at concentrations of 31.2 and 62.5 μM reduced the worm motor activity and caused the death of all male and female schistosomes, respectively. In addition, confocal laser scanning microscopy revealed morphological alterations on the tegument of worms such as disintegration, sloughing and erosion of the surface, and a correlation between viability and tegumental damage was observed. In conclusion, nerolidol may be a promising lead compound for the development of antischistosomal natural agents.

Figure 1

Chemical structure of nerolidol: cis-3,7,11-trimethyl-1,6,10-dodecatrien-3-ol and trans-3,7,11-trimethyl-1,6,10-dodecatrien-3-ol.

Figure 2

In vitro effect of nerolidol on the survival of Schistosoma mansoni after 24 h (A), 48 h (B) and 120 h (C) of treatment. Pairs of adult worms, males (closed bars) and females (open bars), were incubated in 24-well culture plates containing RPMI 1640 medium and treated with nerolidol at different concentrations. Mortality data are presented from ten worm couples and values correspond to the sum of the adult schistosomes obtained from three separate experiments performed in triplicate (n = 2) and quadruplicate (n = 1).

Figure 3

Microscopy investigation of Schistosoma mansoni male worm after in vitro incubation with nerolidol. After 5 days or in the case of death, schistosomes were fixed and monitored using a confocal microscopy. (A) Negative control. (B) 62.5 µM nerolidol. (C) 125 µM nerolidol. (D) 250 µM nerolidol. Scale bars = 50 µm.

Figure 4

Morphological changes on the tegument of S. mansoni male worms after treatment with nerolidol. Quantitative analysis, measured in a 20,000 µm² of area in a dorsal region of male parasite, was performed using three-dimensional images obtained from confocal microscope (see Figure 3). A minimum of three tegument areas of each parasite were assessed. Values are means ± SD (bars) of ten male adult worms. *** p < 0.001 compared with untreated groups.