Anti-giardia activity of hexane extract of Citrus aurantifolia (Christim) swingle and some of its constituents

Background: Giardia lamblia is a parasite that causes giardiasis in humans and other mammals. The common treatment includes different drugs, which were described to produce unpleasant side effects. Citrus aurantifolia, popularly known as “lima”, is a plant used in traditional medicine to treat gastrointestinal symptoms. The aim of the present study was to evaluate the anti-Giardia activity of 10 pure compounds obtained from a hexanic extract of Mexican lime on the basis of trophozoite growth inhibition.Materials and Methods: A hexanic extract obtained from fresh fruit peels of Citrus aurantifolia was tested on G. lamblia strain 0989:IMSS trophozoites cultured in TYI-S-33 medium. The concentration of all standard drugs, analyzed by gas chromatography, was adjusted at 10 mg/mL. Metronidazole was used as a positive control. Growth inhibition was determined by counting the number of trophozoites using a Neubauer chamber. The 50% inhibitory concentration (IC50) of each drug was calculated by probit analysis and 95% confidence limits were calculated.Results: 4-hexen-3-one, citral and geraniol showed IC50 values of 34.2, 64.5 and 229.49 μg/ml in axenic cultures after 24 hr of incubation, respectively. When these results were compared with a positive control of metronidazole; 4-hexen-3-one was 66 times; citral was 112 and geraniol was 441 times less active respectively. The other tested compounds did not inhibit the growth of cultured G. lamblia trophozoites.Conclusion: The obtained results lead us to propose that these tested compounds from C. aurantifolia have potential for use as therapeutic agents against giardiasis.Keywords: antigiardial ; Citrus aurantifolia; antiprotozoal activity; Giardia lambli

Exploiting evolutionary steering to induce collateral drug sensitivity in cancer

Drug resistance mediated by clonal evolution is arguably the biggest problem in cancer therapy today. However, evolving resistance to one drug may come at a cost of decreased fecundity or increased sensitivity to another drug. These evolutionary trade-offs can be exploited using 'evolutionary steering' to control the tumour population and delay resistance. However, recapitulating cancer evolutionary dynamics experimentally remains challenging. Here, we present an approach for evolutionary steering based on a combination of single-cell barcoding, large populations of 108-109 cells grown without re-plating, longitudinal non-destructive monitoring of cancer clones, and mathematical modelling of tumour evolution. We demonstrate evolutionary steering in a lung cancer model, showing that it shifts the clonal composition of the tumour in our favour, leading to collateral sensitivity and proliferative costs. Genomic profiling revealed some of the mechanisms that drive evolved sensitivity. This approach allows modelling evolutionary steering strategies that can potentially control treatment resistance