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Review
. 2018 Jun 22;8:209.
doi: 10.3389/fcimb.2018.00209. eCollection 2018.

Flavonoids as a Natural Treatment Against Entamoeba histolytica

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Free PMC article
Review

Flavonoids as a Natural Treatment Against Entamoeba histolytica

Moisés Martínez-Castillo et al. Front Cell Infect Microbiol. .
Free PMC article

Abstract

Over the past 20 years, gastrointestinal infections in developing countries have been a serious health problem and are the second leading cause of morbidity among all age groups. Among pathogenic protozoans that cause diarrheal disease, the parasite Entamoeba histolytica produces amebic colitis as well as the most frequent extra-intestinal lesion, an amebic liver abscess (ALA). Usually, intestinal amebiasis and ALA are treated with synthetic chemical compounds (iodoquinol, paromomycin, diloxanide furoate, and nitroimidazoles). Metronidazole is the most common treatment for amebiasis. Although the efficacy of nitroimidazoles in killing amebas is known, the potential resistance of E. histolytica to this treatment is a concern. In addition, controversial studies have reported that metronidazole could induce mutagenic effects and cerebral toxicity. Therefore, natural and safe alternative drugs against this parasite are needed. Flavonoids are natural polyphenolic compounds. Flavonoids depend on malonyl-CoA and phenylalanine to be synthesized. Several flavonoids have anti-oxidant and anti-microbial properties. Since the 1990s, several works have focused on the identification and purification of different flavonoids with amebicidal effects, such as, -(-)epicatechin, kaempferol, and quercetin. In this review, we investigated the effects of flavonoids that have potential amebicidal activity and that can be used as complementary and/or specific therapeutic strategies against E. histolytica trophozoites. Interestingly, it was found that these natural compounds can induce morphological changes in the amebas, such as chromatin condensation and cytoskeletal protein re-organization, as well as the upregulation and downregulation of fructose-1,6-bisphosphate aldolase, glyceraldehyde-phosphate dehydrogenase, and pyruvate:ferredoxin oxidoreductase (enzymes of the glycolytic pathway). Although the specific molecular targets, bioavailability, route of administration, and doses of some of these natural compounds need to be determined, flavonoids represent a very promising and innocuous strategy that should be considered for use against E. histolytica in the era of microbial drug resistance.

Keywords: Entamoeba histolytica; alternative treatment; anti-inflammatory response; anti-oxidants; flavonoids; metronidazole.

Figures

Figure 1
Figure 1
General structure of flavonoids.
Figure 2
Figure 2
Effects of flavonoids in pathogenic protozoa.
Figure 3
Figure 3
Structures of flavonoids with anti-amebic properties.
Figure 4
Figure 4
Flavonoids and their possible targets on E. histolytica. (A) Natural source of flavonoids with anti-amebic activity, fruits (grapes), seeds (cacao), and flowers (Geranium mexicanum). (B) Potential cellular targets in the ameba. Alteration of DNA replication and apoptosis induction; dysregulation of cytoplasmic proteins: HSP70, PFOR, G/FBPA, and GAPDH; inhibition of cytotoxicity, phagocytosis and alteration of the trophozoite migration (myosin II heavy chain, alpha-actinin, actin, and cortexillin II).
Figure 5
Figure 5
Possible effects of flavonoids in the regulation of biochemical and immunological responses against amebiasis. (A) Recruitment of neutrophils and macrophages by E. histolytica promoting the synthesis and production of pro-inflammatory cytokines and oxidative mediators. E. histolytica presents detoxifying enzymes. (B) Possible mechanisms of the flavonoids as direct scavenger of ROS, ONOO, and NO, enhancer of CAT, SOD, and GPx enzymes and regulation of inflammation via STAT and NF-κB. Effect of the flavonoids in neutrophils (MPO production), macrophages (decrease of inflammatory mediators), and E. histolytica trophozoites (direct damage in different molecular targets).

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