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Ascorbic acid potentiates the Giardia duodenalis growth inhibitory activity of pure Terminalia ferdinandiana Exell compounds

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Abstract

Giardiasis, one of the most common causes of diarrhoeal disease, is caused by gastrointestinal protozoal parasites of the genus Giardia. Metronidazole is the most commonly used drug to treat giardiasis. However, metronidazole resistance is increasingly common, making the development of new anti-giardial drugs a high priority. A panel of 11 compounds previously identified in T. ferdinandiana fruit extracts were investigated for the ability to inhibit G. duodenalis proliferation. Eight of the 11 compounds inhibited the growth of all three G. duodenalis strains. 2,3-Dihydroxyphenyl B-D-glucopyranosiduronic acid (DPGA) was the most potent anti-giardial compound, with IC50 values as low as 126 μM (38 μg/mL). Notably, DPGA inhibited a metronidazole-resistant G. duodenalis strain with similar activity as determined for the metronidazole-sensitive strains. Furthermore, the activity of DPGA was greatly potentiated when it was tested in combination with ascorbic acid, to approximately 17 μM (5 μg/mL) for the metronidazole-sensitive G. duodenalis strains and 40 μM (12 mg/mL) for the resistant strain. The T. ferdinandiana tannins (gallic acid and chebulic acid) were moderate inhibitors of G. duodenalis growth when tested in combination with ascorbic acid, although they had only low levels of activity when tested alone. All of the tested compounds (and their combinations with ascorbic acid) displayed low toxic effects and all compounds are conformed to Lipinski’s rules of 5 with few violations, indicating their potential as drug leads and chemotherapies for the treatment and prevention of giardiasis.

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Acknowledgements

The authors are thankful to Prof Ann MacDonnell for the gift of the sheep S2 G. duodenalis strain used in these studies. We are also grateful to David Boehme of Wild Harvest, Northern Territory, Australia for providing the T. ferdinandiana fruit pulp used in these studies.

Funding

Financial support for this work was provided by Plum Landholdings, Australia.

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Authors and Affiliations

  1. Environmental Futures Research Institute, Nathan Campus, Griffith University, 170 Kessels Rd, Nathan, Queensland, 4111, Australia

    I. E. Cock & P. Rayan

  2. School of Environment and Science, Nathan Campus, Griffith University, 170 Kessels Rd, Nathan, Queensland, 4111, Australia

    I. E. Cock & P. Rayan

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  1. I. E. Cock
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  2. P. Rayan
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Correspondence to I. E. Cock.

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Cock, I.E., Rayan, P. Ascorbic acid potentiates the Giardia duodenalis growth inhibitory activity of pure Terminalia ferdinandiana Exell compounds. Parasitol Res 119, 1125–1137 (2020). https://doi.org/10.1007/s00436-019-06579-1

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  • DOI: https://doi.org/10.1007/s00436-019-06579-1

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