Evidence map›Paper›PMID 26939119›Full record

ArticlePloS one2016

Mode of Action of the Sesquiterpene Lactones Psilostachyin and Psilostachyin C on Trypanosoma cruzi.

Valeria P Sülsen, Vanesa Puente, Daniela Papademetrio, Alcira Batlle, Virginia S Martino, Fernanda M Frank, María E Lombardo

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
6.4field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 54 citations in OpenAlex.

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  7. Current trends in the pharmacological management of Chagas disease.International journal for parasitology. Drugs and drug resistance · 2020
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  10. New heteroleptic oxidovanadium(V) complexes: synthesis, characterization and biological evaluation as potential agents against Trypanosoma cruzi.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2018
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Valeria P SülsenCátedra de Farmacognosia, Instituto de Química y Metabolismo del Fármaco (Universidad de Buenos Aires - Consejo Nacional de Investigaciones Científicas y Técnicas), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
Vanesa PuenteCentro de Investigaciones sobre Porfirinas y Porfirias (Universidad de Buenos Aires - Consejo Nacional de Investigaciones Científicas y Técnicas), Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, Buenos Aires, Argentina.
Daniela PapademetrioCátedra de Inmunología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
Alcira BatlleCentro de Investigaciones sobre Porfirinas y Porfirias (Universidad de Buenos Aires - Consejo Nacional de Investigaciones Científicas y Técnicas), Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, Buenos Aires, Argentina.
Virginia S MartinoCátedra de Farmacognosia, Instituto de Química y Metabolismo del Fármaco (Universidad de Buenos Aires - Consejo Nacional de Investigaciones Científicas y Técnicas), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
Fernanda M FrankCátedra de Inmunología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
María E LombardoCentro de Investigaciones sobre Porfirinas y Porfirias (Universidad de Buenos Aires - Consejo Nacional de Investigaciones Científicas y Técnicas), Hospital de Clínicas José de San Martín, Universidad de Buenos Aires, Buenos Aires, Argentina.
Hospital de Clínicas "José de San Martín" · ARUniversity of Buenos Aires · ARConsejo Nacional de Investigaciones Científicas y Técnicas · AR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Trypanosoma cruzi is the causative agent of Chagas' disease, which is a major endemic disease in Latin America and is recognized by the WHO as one of the 17 neglected tropical diseases in the world. Psilostachyin and psilostachyin C, two sesquiterpene lactones isolated from Ambrosia spp., have been demonstrated to have trypanocidal activity. Considering both the potential therapeutic targets present in the parasite, and the several mechanisms of action proposed for sesquiterpene lactones, the aim of this work was to characterize the mode of action of psilostachyin and psilostachyin C on Trypanosoma cruzi and to identify the possible targets for these molecules. Psilostachyin and psilostachyin C were isolated from Ambrosia tenuifolia and Ambrosia scabra, respectively. Interaction of sesquiterpene lactones with hemin, the induction of oxidative stress, the inhibition of cruzipain and trypanothione reductase and their ability to inhibit sterol biosynthesis were evaluated. The induction of cell death by apoptosis was also evaluated by analyzing phosphatidylserine exposure detected using annexin-V/propidium iodide, decreased mitochondrial membrane potential, assessed with Rhodamine 123 and nuclear DNA fragmentation evaluated by the TUNEL assay. Both STLs were capable of interacting with hemin. Psilostachyin increased about 5 times the generation of reactive oxygen species in Trypanosoma cruzi after a 4h treatment, unlike psilostachyin C which induced an increase in reactive oxygen species levels of only 1.5 times. Only psilostachyin C was able to inhibit the biosynthesis of ergosterol, causing an accumulation of squalene. Both sesquiterpene lactones induced parasite death by apoptosis. Upon evaluating the combination of both compounds, and additive trypanocidal effect was observed. Despite their structural similarity, both sesquiterpene lactones exerted their anti-T. cruzi activity through interaction with different targets. Psilostachyin accomplished its antiparasitic effect by interacting with hemin, while psilostachyin C interfered with sterol synthesis.

Indexed as

AmbrosiaApoptosisChagas DiseaseHeminHeterocyclic Compounds, 3-RingHumansLactonesPlant ExtractsPyronesReactive Oxygen SpeciesSesquiterpenesTrypanosoma cruziHeminHeterocyclic Compounds, 3-RingLactonesPlant Extractspsilostachyin Apsilostachyin CPyronesReactive Oxygen SpeciesSesquiterpenes

Identifiers

PMID26939119
PMCPMC4777292
OpenAlexW2291024452

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.