Evidence map›Paper›PMID 25313212›Full record

ArticleAntimicrobial agents and chemotherapy2015

Probing the molecular mechanism of hypericin-induced parasite death provides insight into the role of spermidine beyond redox metabolism in Leishmania donovani.

Shalini Singh, Shyamali Sarma, Shashank P Katiyar, Mousumi Das, Ruchika Bhardwaj, Durai Sundar, Vikash Kumar Dubey

Open access · bronzeAbstract read
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Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
3.2field-weighted citation impact, top 9% 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

15 citing papers in PubMed, 42 citations in OpenAlex.

  1. Article
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  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Pharmaceuticals (Basel, Switzerland) · 2022
    Article
  10. Polyamine Metabolism inMedical sciences (Basel, Switzerland) · 2022
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
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 2 institutions in 1 country.

Shalini SinghDepartment of Biotechnology, Indian Institute of Technology Guwahati, Guwahati, India.
Shyamali SarmaDepartment of Biotechnology, Indian Institute of Technology Guwahati, Guwahati, India.
Shashank P KatiyarDepartment of Biochemical Engineering and Biotechnology, Indian Institute of Technology Delhi, New Delhi, India.
Mousumi DasDepartment of Biotechnology, Indian Institute of Technology Guwahati, Guwahati, India.
Ruchika BhardwajDepartment of Biotechnology, Indian Institute of Technology Guwahati, Guwahati, India.
Durai SundarDepartment of Biochemical Engineering and Biotechnology, Indian Institute of Technology Delhi, New Delhi, India.
Vikash Kumar DubeyDepartment of Biotechnology, Indian Institute of Technology Guwahati, Guwahati, India vdubey@iitg.ernet.in.
Indian Institute of Technology Guwahati · INIndian Institute of Technology Delhi · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hypericin, a natural compound from Hypericum perforatum (St. John's wort), has been identified as a specific inhibitor of Leishmania donovani spermidine synthase (LdSS) using integrated computational and biochemical approaches. Hypericin showed in vitro inhibition of recombinant LdSS enzyme activity. The in vivo estimation of spermidine levels in Leishmania promastigotes after hypericin treatment showed significant decreases in the spermidine pools of the parasites, indicating target specificity of the inhibitor molecule. The inhibitor, hypericin, showed significant antileishmanial activity, and the mode of death showed necrosis-like features. Further, decreased trypanothione levels and increased glutathione levels with elevated reactive oxygen species (ROS) levels were observed after hypericin treatment. Supplementation with trypanothione in the medium with hypericin treatment restored in vivo trypanothione levels and ROS levels but could not prevent necrosis-like death of the parasites. However, supplementation with spermidine in the medium with hypericin treatment restored in vivo spermidine levels and parasite death was prevented to a large extent. The data overall suggest that the parasite death due to spermidine starvation as a result of LdSS inhibition is not related to elevated levels of reactive oxygen species. This suggests the involvement of spermidine in processes other than redox metabolism in Leishmania parasites. Moreover, the work provides a novel scaffold, i.e., hypericin, as a potent antileishmanial molecule.

Indexed as

AnimalsAnthracenesAntiprotozoal AgentsEnzyme InhibitorsGlutathioneLeishmania donovaniMacrophagesOxidation-ReductionPeryleneReactive Oxygen SpeciesSpermidineSpermidine SynthaseAnthracenesAntiprotozoal AgentsEnzyme InhibitorsGlutathionehypericinPeryleneReactive Oxygen SpeciesSpermidineSpermidine Synthasetrypanothione

Identifiers

PMID25313212
PMCPMC4291343
OpenAlexW1974302823

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Registered trials

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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 OpenQuestion graph.