Short Communication ISSN: 2574 -1241 DOI: 10.26717/BJSTR.2020.30.004895 Catechins as Emerging and Promising Antiparasitic Agents Raúl Argüello-García*1 and Geovanna Nallely Quiñonez-Bastidas2 11Departamento de Genética y Biología Molecular, México 2Departamento de Farmacia, Facultad de Química, México *Corresponding author: Raul Arguello Garcia, Departamento de Genética y Biología Molecular, CINVESTAV-IPN, 07360 México City, México ARTICLE INFO ABSTRACT Received: August 17, 2020 Catechins are polyphenols present in green tea and other plant species as a defense Published: against pathogen insults that profile their health-promoting and anti-infectious activities September 07, 2020 in humans. Worth noting their anti-parasite effects have emerged in recent years. In this Citation: Giardia, Entamoeba) and intracellular, apicomplexan Nallely Quiñonez-Bastidas. Catechins as review,Plasmodium we focus on the effect of catechinsTrypanosoma over, growthLeishmania and )pathogenic protozoa and mechanisms nematodes of of a Emerging Raúland Argüello-García,Promising Antiparasitic Geovanna variety of extracellular,Teladorsagia anaerobic, Trichostrongylus( , Ascaris and Haemonchus ( ) and kinetoplastid ( 2020. BJSTR. MS.ID.004895. livestock impact as . Moreover, Agents. Biomed J Sci & Tech Res 30(1)- an inhibitory effect of (galloyl)-catechins on allergenic proteases from mites has been secondaryreported. Altogether,effects and drugthese resistance data pinpoint in parasitic (galloyl)-catechins infections. as candidates for novel alternatives in therapeutic intervention and therapy-associated problems, such as Introduction Figure 1: Chemical structures of catechin monomers and oligomers included in this work. Copyright@ Raúl Argüello-García | Biomed J Sci & Tech Res | BJSTR. MS.ID.004895. 23065 Volume 30- Issue 1 DOI: 10.26717/BJSTR.2020.30.004895 Acacia catechu Giardia duodenalis and Entamoeba histolytica L.f Catechins (from “catechu”, a boiled extract from that have pathogenic ) are a group of polyphenol compounds from plants classified (trophozoite) and infectious (cyst) stages and are commonly in vitro within the subclass known as flavan-3-ols (flavanols) of the flavonoid associated to infectious diarrhea. In studies on inhibition of family. Flavanols include the precursor isomers (+)-catechin (C) trophozoite growth using a set of 18 plant flavonoids that and (-)-epicatechin (EC), as well as, their gallate ester derivatives: included three catechins, (-)-EC and (-)-EGC were the two most Helianthemum glomeratum (-)-epigallocatechingallate (EGCG), (-)-epicatechingallate (ECG) and potent compounds whilst (+)-Cat had the sixth efficacy against Geranium mexicanum (-)-epigallocatechin (EGC) along to their corresponding epimers: these two pathogens [15]. Likewise roots and aerial parts of Rubus coriifolius (+)-gallocatechingallate (GCG) and (+)-gallocatechin (GC)(Figure (-)-EC and (+)-Cat were isolated from both Camellia sinensis), Theobroma 1). Catechins are abundant in extracts derived from the tea plant Focke, with the former cacao seeds), these are also found in many other plant species ( in cocoa and some chocolates (from being the most effective antiamoebic and antigiardial component medicinal plant, Helianthemum glomeratum and the latter displaying moderate activity [16,17]. Other Mexican and are present in human diet within common foodstuffs, herbal contained both (-)-EGC Giardia and Entamoeba remedies, dairy products, fruits (apple, grape, berries), vegetables and (-)-EGCG of which the former was equipotent to (-)-EC and the condensation complexes. One major class of condensed catechins and in wine as well [1,2]. Catechins are also found as polymeric latter to (+)-Cat against [18]. These results minus isomer hence in cis give evidence on the importance of the presence of 3-OH group (as is the proanthocyanidin group, also called as “condensed tannins”, -configuration with B-ring) for higher phloroglucinols and resorcinols. Among these, procyanidins and comprising two main categories based on A-ring substitutions: antiamoebic and antigiardial activities of catechin monomers. In prodelphinidins are the phloroglucinol-type proanthocyanidins addition the precursor (+)-Cat and the derivative catechin-3-O-α-L- Osyris alba rhamnopyranoside isolated from the dioecious hemiparasite shrub50 most found in (Figure 1). Otherwise during fermentation of black displayed a toxicity almost 20-fold lower (i.e. higher IC against Giardia and Entamoeba. tea the reddish thearubigins that result from condensation of EGC values) against cancer (Hep-2) and non-malignant (Vero) cells than and EGCG, namely theaflavins, are formed [3] (Figure 1). Metronidazole, a current drug of choice against these parasites Since the past two decades, there has been an increasing interest to consider catechins as an alternative for pharmacological but with emerging evidence of drug-resistance [19] and variable intervention in a spectrum of therapeutic issues as diabetes, drug susceptibility [20] exhibited a toxicity index better by far neuropathic pain, obesity, neurodegenerative disorders and (above 200-fold); however catechins have still a promisingly antimicrobial activities [4-8]. In general, the diverse activities favorable profile for further preclinical tests [21]. Consistent50 to G. duodenalis than displayed by catechins and condensed tannins are dependent this notion, (-)-EC had a better efficacy (i.e. lower ED values) on the catechin type, suggesting a clear influence of the galloyl in CD-1 mice experimentally infected with isolated from the Mexican medicinal plants G. mexicanum, Cuphea moiety [9-12]. On the other hand, pathogenic organisms as endo- metronidazole and other flavonoids as kaempferol and tiliroside pinetorum, H. glomeratum and R. coriifolius parasites (protozoa and helminthes) and ecto-parasites (e.g. mites) are major but often neglected infectious agents causing severe [22]. The mechanism health problems of high morbidity and/or mortality in clinical of catechin-induced cell death in these two protozoa harbouring Entamoeba and veterinary practice. These are transmitted by multiple routes: mitosomes instead typical mitochondria has not been elucidated waterborne, foodborne, by soil or vectors and have complex life but trophozoites exposed to (-)-EC displayed chromatin cycles involving, importantly, multiple morphological stages that clumping, increased glycogen deposits, reduced number and size have limited the establishment of effective vaccines. Also, side of cytoplasmic vacuoles and alteration of cytoskeletal functions effects of and resistance to prescribed drugs are reportedly growing [23,24]. These features resemble programmed cell death (PCD)- stress-inducing agents in this organism. issues that make necessary a continuous search for new and safer like induced by protein translation inhibitors and nitrosative antiparasitic compounds [13]. In this context, the recent completion Regarding oligomeric catechins, in roots of the plant Geranium of parasite genome sequencing projects provides a useful platform niveum towards drug target deconvolution along to molecular databases -8,2 -O-7)-afzelechin and agents. two uncommon A-type proanthocyanidins, named as (chemicals, proteins) to decipher the mode of action of parasiticidal -8,2 Geranins A and B [epiafzelechin-(4β β Antiprotozoal Action of Catechins epi-catechin-(4β β-O-7)-afzelechin respectively] were initially Giardia Protozoa include unicellular eukaryotes that account for isolated and showed inhibitory effect on the growth of both parasites E. histolytica trophozoites albeit was highly susceptible to both compounds and Geranin A had a much lower efficacy on 30% of all known parasite species (21 out of 69) causing human -8,2 -8,2 -O-7)- [25]. Further isolation of Geranins C and D [epi-afzelechin- disease that usually requires therapeutic intervention [14]. In -8,2 against extracellular, intestinal, and microaerophilic protozoa as (4β β–O-7)-gallocatechin and epi-afzelechin-(4β β this scenario, various monomeric catechins have been tested afzelechin-(4β β-O-7)-afzelechin respectively] rendered a moderate activity for the Geranin D against both parasites while Copyright@ Raúl Argüello-García | Biomed J Sci & Tech Res | BJSTR. MS.ID.004895. 23066 Volume 30- Issue 1 DOI: 10.26717/BJSTR.2020.30.004895 E. histolytica P. falciparum–infected erythrocytes to ICAM- Giardia and Geranin C was moderately active only against [26]. to block the binding of Entamoeba. Thus, the efficacy order for Geranins was A>B>D>C for 1 that is exposed on endothelial cell surface, an event associated to parasite isolates in the range 37-80% at 50µ B>D>C>AOther forgroup of protozoa is the kinetoplastids causing Chagas pathology in malaria [36]. Moreover, this inhibition varied amongst T. cruzi M EGCG, which was Leishmania major, L. amazonensis and suggested to mimic the L43 loop of ICAM-1 [37]. Also, the membrane disease ( ) and the cutaneous/mucocutaneous/visceral L. donovani permeabilizer digitonin synergized the cytotoxicity of EGCG against leishmaniasis complex (e.g. liver sporozoites and additively inhibited parasite motility [38]. respectively). In Chagas disease and Leishmaniasis, macrophages or tissue cells and extracellular trypomastigote/ Furthermore, EGCG exhibits disaggregating effect on amyloid-like these organisms have the intracellular amastigote stage within T. cruzi Leishmania fibrils formed by the vaccine candidate merozoite surface protein-2 P. falciparum (MSP-2) causing oligomer release [39]. In addition,