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Piqueria trinervia as a source of metabolites against Giardia intestinalis.

ABSTRACT: CONTEXTPiqueria trinervia Cav. (Asteraceae) is a plant species with a long history in traditional medicine to cure diarrhoea and other digestive disorders.OBJECTIVEThe study investigates the antigiardial activity of piquerol, trinervinol, red oil and two fractions (F1 and F2) from P. trinervia.MATERIALS AND METHODSP. trinervia was collected in the Ajusco in Mexico City. Aerial parts were ground and mixed with water to obtain the extract, which was treated with dichloromethane to isolate piquerol and trinervinol (P & T). Remnants were the red oil, fractions 1 and 2 (RO, F1 & F2). Trophozoites of Giardia intestinalis were treated with P, T, RO, F1 and F2 at different concentrations (0.78-200??g/mL) for 48?h. Antigiardial activity was measured using the methylene blue reduction, and the cytotoxicity assayed on human fibroblasts and Vero cells by reduction of tetrazolium salts.RESULTSTrinervinol and piquerol showed antigiardial activity with an IC50?=?2.03 and 2.42??g/mL, and IC90?=?13.03 and 8.74??g/mL, respectively. The concentrations of trinervinol (CC50?=?590??g/mL) and piquerol (CC50?=?501??g/mL) were not cytotoxic to human fibroblasts.CONCLUSIONSCompounds from P. trinervia showed antigiardial activity; to enhance this activity, piquerol and trinervinol can be chemically modified.

SUBMITTER: Rufino-Gonzalez Y

PROVIDER: S-EPMC6130510 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Piqueria trinervia as a source of metabolites against Giardia intestinalis.

Rufino-González Yadira Y Ponce-Macotela Martha M Jiménez-Estrada Manuel M Jiménez-Fragoso Candy N CN Palencia Guadalupe G Sansón-Romero Gabriel G Anzo-Osorio Anahi A Martínez-Gordillo Mario N MN

Pharmaceutical biology 20171201 1

<h4>Context</h4>Piqueria trinervia Cav. (Asteraceae) is a plant species with a long history in traditional medicine to cure diarrhoea and other digestive disorders.<h4>Objective</h4>The study investigates the antigiardial activity of piquerol, trinervinol, red oil and two fractions (F1 and F2) from P. trinervia.<h4>Materials and methods</h4>P. trinervia was collected in the Ajusco in Mexico City. Aerial parts were ground and mixed with water to obtain the extract, which was treated with dichloro ...[more]

PMID: 28524742

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Project description:BackgroundThe unicellular protozoan parasite Giardia intestinalis, which primarily infects humans and animals such as cattle and sheep, is having a major negative impact on public health. Giardia is able to evade the recognition and elimination of the host immune system because of the trophozoite surface and extracellular vesicles (EVs) covered by variant-specific surface proteins (VSPs). As key proteins for immune evasion, whether VSPs can regulate Giardia-induced pyroptosis and promote Giardia evasion of host immune responses has not been reported.MethodsTo examine the role of Giardia VSPAS7 on Giardia-induced activation of the signaling pathway, secretion of pro-inflammatory cytokines, pyroptosis and the mechanism involved, we constructed the pcDNA3.1-vspas7 expression plasmid and transfected this plasmid into mouse macrophages. Key proteins for pyroptosis, IL-1β secretion and LDH release were detected in pcDNA3.1-vspas7-transfected wild-type (WT) cells and NLRP3-deficient cells by western blot, ELISA and LDH assays, respectively. The interactions of Giardia VSPAS7 and mouse NLRP3 were examined using immunofluorescence assays (IFA), co-immunoprecipitation (Co-IP) and bimolecular fluorescence complementation (BiFC) assays.ResultsVSPAS7 could decrease the levels of phosphorylated-p65 (P-p65), P-IκBα and P-ERK caused by Giardia and reduce the production levels of Giardia-induced pro-inflammatory cytokine IL-6, IL-12 p40 and TNF-α. The results showed that VSPAS7 inhibited Giardia-mediated activation of NF-κB, ERK/MAPK signaling and secretion of pro-inflammatory cytokines. Furthermore, VSPAS7 suppressed Giardia-induced macrophage pyroptosis by reducing GSDMD cleavage, caspase-1 activation, IL-1β secretion and LDH release. We further found that VSPAS7 could interact with mouse NLRP3 directly, and in NLRP3-deficient cells the suppression of Giardia-induced macrophage pyroptosis by VSPAS7 was significantly attenuated.ConclusionsOverall, VSPAS7 could inhibit Giardia-induced activation of signaling pathways and pyroptosis in host macrophages, allowing Giardia evasion of host immune responses. Studies on Giardia VSP-mediated immune evasion provide an important theoretical basis for in-depth studies on Giardia pathogenicity.

Dataset Information

Piqueria trinervia as a source of metabolites against Giardia intestinalis.

Publications

Piqueria trinervia as a source of metabolites against Giardia intestinalis.

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