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

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 with potent G. duodenalis growth inhibitory activity 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-Dglucopyranosiduronic acid (DPGA)DPGA was the most potent anti-giardial compound, with IC50 values as low as 126μM (38µg/mL). Notably, DPGA inhibited a metronidazole resistant G. duodenalis strain with similar potency as determined for the metronidazole sensitive strains. Furthermore, the potency of DPGA was greatly potentiated when it was tested in combination with ascorbic acid, to approximately 17μM (5µg/mL) for the metronidazole sensitive G. duodenalis strains and 40μM (12mg/mL) for the resistant strain. The T. ferdinandiana tannins (gallic acid and chebulic acid) were also 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 and all compounds 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.

Antimicrobial resistance of the enteric protozoon Giardia duodenalis – A narrative review

“…Also, methylgerambullin, a sulphur-containing amide in Glycosmis spp. (family Rutacea e) [ 131 ], 2,3-Dihydroxyphenyl B-D-glucopyranosiduronic acid as well as the tannins gallic acid and chebulic acid extracted from Terminalia ferdinandiana in combination with ascorbic acid, respectively [ 132 ], and crude Ageratum conyzoides extracts [ 133 ] showed giardicidal effects in vitro and partly also in animal experiments. The giardicidal effects of the latter were associated with changes in the flagella and the ventral discs of G. duodenalis trophozoites [ 133 ].…”

Male Swiss mice (Mus musculus) as a most suitable experimental model for the study of Giardia duodenalis BIV

“…The etiologic agent of giardiasis, Giardia duodenalis (synonyms: Giardia lamblia and Giardia intestinalis) is one of the most prevalent protozoa in the human gastrointestinal tract (Colli et al, 2015;Hooshyar et al, 2019), and the most associated with cases of infectious diarrhea (Cock et al, 2020), which are an important cause of morbimortality in children under five years old (Baker & Alonso, 2018). Transmission is via the fecal-oral route and occurs mainly by accidental ingestion of cysts in contaminated water and food, being favored by the absence of water and sewage treatment systems, and by the conglomerate of people (Fantinatti et al, 2016).…”

Davidsonia pruriens F. Muell. Fruit and Leaf Extracts Lack Antibacterial and Antifungal Activity

“…has been particularly well studied and has been reported to have anticancer activity, 27,28 anti-inflammatory activity 29 and anti-giardial activity. 30,31 It also has potent antibacterial activity, [32][33][34][35] including a methicillin resistant strain of Staphylococcus aureus (MRSA). 36 Tasmannia lanceolata R. Br.…”