Abstract

In Mexico, the Adenophyllum aurantium (L.) Strother plant is consumed as an infusion to treat intestinal diseases such as amoebiasis, which is an endemic health problem in Mexico and other countries. However, the effect of A. aurantium on Entamoeba histolytica, the causative agent of amoebiasis, is unknown. An aerial part methanolic extract (AaMeA), a root methanolic extract (AaMeR) and a root ethyl acetate extract (AaEaR) were tested on E. histolytica trophozoites. AaMeA and AaMeR did not show antiproliferative activity; however, AaEaR exhibited an in vitro GI50 of 230 μg/ml, and it was able to inhibit the differentiation of Entamoeba invadens trophozoites into cysts. The intraperitoneal administration of AaEaR (2.5 or 5 mg) to hamsters that were infected with E. histolytica inhibited the development of amoebic liver abscesses in 48.5 or 89.0% of the animals, respectively. Adhesion to fibronectin and erythrophagocytosis were 28.7 and 37.5% inhibited by AaEaR, respectively. An ultrastructure analysis of AaEaR-treated trophozoites shows a decrease in the number of vacuoles but no apparent cell damage. Moreover, this extract affected the actin cytoskeleton structuration, and it prevented the formation of contractile rings by mechanism(s) that were independent of reactive oxygen species and RhoA activation pathways. 13C NMR data showed that the major compounds in the AaEaR extract are thiophenes. Our results suggest that AaEaR may be effective in treatments against amoebiasis, nevertheless, detailed toxicity studies on thiophenes, contained in AaEaR, are required to avoid misuse of this vegetal species.

Highlights

  • Amoebiasis is the third-most common cause of death from parasitic infections, and it has a very high incidence in countries such as India, Mexico, Central and South America, and others

  • We decide to analyze the effect on the proliferation of E. histolytica trophozoites, of a methanolic extract of the aerial part (AaMeA), a methanolic extract of the root (AaMeR) and an ethyl acetate extract of the root (AaEaR), all of them at 200 μg/ml

  • AaEaR (GI50: 230 μg/ml) could be classified as a weak antiamoebic extract; this particular classification was defined by using a small initial number of amoebas (6 × 103) in comparison with the numbers used in this study (1 × 104), and the capability of the extract may be underestimated

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Summary

Introduction

Amoebiasis is the third-most common cause of death from parasitic infections, and it has a very high incidence in countries such as India, Mexico, Central and South America, and others. Entamoeba histolytica is a protozoan parasite and the causative agent of this disease, which is associated with intestinal and extra-intestinal clinical manifestations. This amoeba has a twostage life cycle, namely, the cyst, which is the infective stage, and the trophozoite, which is the invasive phase. The infection is acquired through food and water that has been contaminated with E. histolytica cysts (Lejeune et al, 2009) These cysts release amoebic trophozoites that may invade the intestinal mucosa and disseminate through a hematogenous route to other organs, primarily the liver, where the parasite usually causes amoebic liver abscess (ALA) formation (Centers for Disease Control and prevention [CDC], 2015). Metronidazole is an effective treatment for invasive amoebiasis, side effects have been described in patients who were treated with this antiamoebic agent, and drug resistance has been reported (Hanna et al, 2000; Upcroft and Upcroft, 2001; Bansal et al, 2004)

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