Identification and molecular characterization of the tubulin‐podophyllotoxin‐type lignans binding site on <i>Giardia lamblia</i>

Gutiérrez-Gutiérrez, Filiberto; Romo-Mancillas, Antonio; Puebla-Pérez, Ana Marı́a; Castillo-Romero, Araceli

doi:10.1111/cbdd.13605

Cited by 4 publications

(3 citation statements)

References 36 publications

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“…The same occurs with podophyllotoxin-type lignans from Bursera fagaroides var. fagaroides , which affect the distribution and staining pattern of microtubular structures on Giardia trophozoites, by the union in colchicine binding site ( Gutiérrez-Gutiérrez et al, 2017b ; Gutiérrez-Gutiérrez et al, 2019 ). On the other hand, it has been shown that paclitaxel is capable of producing microtubule stabilization, thereby generating a significant increase in the size of both the median body and the eight axonemes ( Dawson et al, 2007 ).…”

Section: Discussionmentioning

confidence: 99%

Polyphenolic extract from Punica granatum peel causes cytoskeleton-related damage on Giardia lamblia trophozoites in vitro

Palomo‐Ligas

Estrada-Camacho

Garza-Ontiveros

et al. 2022

PeerJ

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Background Diarrheal diseases caused by protozoa have a great impact on human health around the world. Giardia lamblia is one of the most common flagellates in the intestinal tract. Factors such as adverse effects to first-line drugs or the appearance of drug-resistant strains, make it necessary to identify new treatment alternatives. Agroindustry waste, like pomegranate peel, are a source of phenolic compounds, which possess antiparasitic activities. In vivo studies demonstrated antigiardiasic potential by reducing cyst shedding and protecting intestinal cells; however, they did not identify the compounds or elucidate any mechanism of action in the parasite. The objective of this study is to identify potential molecular targets and to test the in vitro effects of polyphenols from Punica granatum on Giardia lamblia. Methods The in vitro antigiardial potential of polyphenolic extract from pomegranate peel (Punica granatum L.) obtained using microwave-ultrasound methodology was evaluated on Giardia lamblia trophozoites. Extract phytochemical identification was performed by HPLC/MS analysis. The effect of polyphenolic extract on growth and adhesion capacity was determined by parasite kinetics; morphological damage was evaluated by SEM, alteration on α-tubulin expression and distribution were analyzed by western blot and immunofluorescence, respectively. Results The pomegranate peel extract showed the presence of ellagitannins (punicalin and punicalagin, galloyl-dihexahydroxydiphenoyl-hexoside), flavones (luteolin), and ellagic acid, that caused an inhibitory effect on growth and adhesion capacity, particularly on cells treated with 200 µg/mL, where growth inhibition of 74.36%, trophozoite adherence inhibition of 46.8% and IC50 of 179 µg/mL at 48 h were demonstrated. The most important findings were that the extract alters α-tubulin expression and distribution in Giardia trophozoites in a concentration-independent manner. Also, an increase in α-tubulin expression at 200 µg/mL was observed in western blot and diffuse or incomplete immunolabeling pattern, especially in ventral disk. In addition, the extract caused elongation, disturbance of normal shape, irregularities in the membrane, and flagella abnormalities. Discussion The pomegranate peel extract affects Giardia trophozoites in vitro. The damage is related to the cytoskeleton, due to expression and distribution alterations in α-tubulin, particularly in the ventral disk, a primordial structure for adhesion and pathogenesis. Microtubule impairment could explain morphological changes, and inhibition of adhesion capacity and growth. Besides, this is the first report that suggests that ellagic acid, punicalin, punicalagin and luteolin could be interactioning with the rich-tubulin cytoskeleton of Giardia. Further investigations are needed in order to elucidate the mechanisms of action of the isolated compounds and propose a potential drug alternative for the giardiasis treatment.

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Section: Discussionmentioning

confidence: 99%

Polyphenolic extract from Punica granatum peel causes cytoskeleton-related damage on Giardia lamblia trophozoites in vitro

Palomo‐Ligas

Estrada-Camacho

Garza-Ontiveros

et al. 2022

PeerJ

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“…The lignans 1-19 have been isolated from specimens of B. fagaroides, collected in México, principally from the bark (Michoacán state) [19,20,26,27,38,39,41,42], two reports from Oaxaca state [25] and one from Guerrero state [42] analyzed the resin. The polarity of the used extracts was chloroform (CHCl 3 ) [25,26], dichloromethane (CH 2 Cl 2 ) [20,38,40,41], ethanol (CH 3 CH 2 OH) [27], CH 3 CH 2 OH 80% (previously treated with hexane) [42], and methanol (CH 3 OH) 70% [19,29,39]. In general, the purification of these extracts was carried out by bioassay-guided chromatographic methods [19].…”

Section: Isolation and Characterizationmentioning

confidence: 99%

“…More recently, the same research group demonstrated that 5′-desmethoxy-peltatin-A-methylether ( 3 ), acetylpodophyllotoxin ( 5 ), and podophyllotoxin ( 1 ) affect the pattern of microtubular structures on Giardia trophozoites. A docking study revealed that the lignans act via binding in a hydrophobic pocket in the heterodimer interface of tubulin in Giardia [ 41 ].…”

Section: Other Effectsmentioning

confidence: 99%

Lignans from Bursera fagaroides: Chemistry, Pharmacological Effects and Molecular Mechanism. A Current Review

Antúnez-Mojica

Romero-Estrada

Hurtado-Díaz

et al. 2021

Life

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Bursera fagaroides is a medicinal tree endemic to México, it belongs to the Burseraceae family and has proven antitumor activity. Modern research, performed principally with the bark extracts, have indicated that lignans are the main active constituents of B. fagaroides, with a high content of aryltetralin, aryldihydronaphtalene, dibenzylbutirolactone, and dibenzylbutane-type lignans as the constituents of the active extracts. In general, lignans from B. fagaroides exhibited potent anti-cancer activity, although antitumor, anti-bacterial, anti-protozoal, anti-inflammatory, and anti-viral properties have also been described. This review covers literature-reported lignans from B. fagaroides, chemical structures, nomenclature, chromatographic techniques of isolation, characterization strategies, and highlights the anti-cancer molecular mechanisms of lignans. Evaluation of the anticancer function of lignans has been extensively investigated since the cytotoxic in vitro results and in vivo assays in mice and zebrafish models to the tubulin molecular recognition by NMR. Also, we discuss the future direction for studying this important plant species and its lignan metabolites.

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Drug resistance in Giardia: Mechanisms and alternative treatments for Giardiasis

Argüello-García

Leitsch

Skinner‐Adams

et al. 2020

Advances in Parasitology

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Identification and molecular characterization of the tubulin‐podophyllotoxin‐type lignans binding site on Giardia lamblia

Cited by 4 publications

References 36 publications

Polyphenolic extract from Punica granatum peel causes cytoskeleton-related damage on Giardia lamblia trophozoites in vitro

Polyphenolic extract from Punica granatum peel causes cytoskeleton-related damage on Giardia lamblia trophozoites in vitro

Lignans from Bursera fagaroides: Chemistry, Pharmacological Effects and Molecular Mechanism. A Current Review

Drug resistance in Giardia: Mechanisms and alternative treatments for Giardiasis

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