Evidence map›Paper›PMID 30870428›Full record

ArticlePLoS neglected tropical diseases2019

Insects in anthelminthics research: Lady beetle-derived harmonine affects survival, reproduction and stem cell proliferation of Schistosoma mansoni.

Josina Kellershohn, Laura Thomas, Steffen R Hahnel, Arnold Grünweller, Roland K Hartmann, Martin Hardt, Andreas Vilcinskas, Christoph G Grevelding, Simone Haeberlein

Open access · goldAbstract read
In one paragraph

Article in PLoS neglected tropical diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.4field-weighted citation impact, top 13% 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

19 citing papers in PubMed, 26 citations in OpenAlex.

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  7. The interaction ofProceedings of the National Academy of Sciences of the United States of America · 2025
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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

9 authors at 2 institutions in 1 country.

Josina KellershohnInstitute of Parasitology, BFS, Justus Liebig University, Giessen, Germany.
Laura ThomasInstitute of Pharmaceutical Chemistry, Philipps University, Marburg, Germany.ORCID 0000-0002-9551-3743
Steffen R HahnelInstitute of Parasitology, BFS, Justus Liebig University, Giessen, Germany.
Arnold GrünwellerInstitute of Pharmaceutical Chemistry, Philipps University, Marburg, Germany.
Roland K HartmannInstitute of Pharmaceutical Chemistry, Philipps University, Marburg, Germany.
Martin HardtBiomedical Research Center Seltersberg-Imaging Unit, Justus Liebig University, Giessen, Germany.
Andreas VilcinskasInstitute for Insect Biotechnology, Justus Liebig University, Giessen, Germany.ORCID 0000-0001-8276-4968
Christoph G GreveldingInstitute of Parasitology, BFS, Justus Liebig University, Giessen, Germany.
Simone HaeberleinInstitute of Parasitology, BFS, Justus Liebig University, Giessen, Germany.ORCID 0000-0002-1932-9696
Justus-Liebig-Universität Gießen · DEPhilipps University of Marburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Natural products have moved into the spotlight as possible sources for new drugs in the treatment of helminth infections including schistosomiasis. Surprisingly, insect-derived compounds have largely been neglected so far in the search for novel anthelminthics, despite the generally recognized high potential of insect biotechnology for drug discovery. This motivated us to assess the antischistosomal capacity of harmonine, an antimicrobial alkaloid from the harlequin ladybird Harmonia axyridis that raised high interest in insect biotechnology in recent years. We observed remarkably pleiotropic effects of harmonine on physiological, cellular, and molecular processes in adult male and female Schistosoma mansoni at concentrations as low as 5 μM in vitro. This included tegumental damage, gut dilatation, dysplasia of gonads, a complete stop of egg production at 10 μM, and increased production of abnormally shaped eggs at 5 μM. Motility was reduced with an EC50 of 8.8 μM and lethal effects occurred at 10-20 μM within 3 days of culture. Enzyme inhibition assays revealed acetylcholinesterase (AChE) as one potential target of harmonine. To assess possible effects on stem cells, which represent attractive anthelminthic targets, we developed a novel in silico 3D reconstruction of gonads based on confocal laser scanning microscopy of worms after EdU incorporation to allow for quantification of proliferating stem cells per organ. Harmonine significantly reduced the number of proliferating stem cells in testes, ovaries, and also the number of proliferating parenchymal neoblasts. This was further supported by a downregulated expression of the stem cell markers nanos-1 and nanos-2 in harmonine-treated worms revealed by quantitative real-time PCR. Our data demonstrate a multifaceted antischistosomal activity of the lady beetle-derived compound harmonine, and suggest AChE and stem cell genes as possible targets. Harmonine is the first animal-derived alkaloid detected to have antischistosomal capacity. This study highlights the potential of exploiting insects as a source for the discovery of anthelminthics.

Indexed as

AlkenesAnimalsAnthelminticsCell SurvivalColeopteraFemaleMaleParasitic Sensitivity TestsReproductionSchistosoma mansoniStem CellsSurvival AnalysisAlkenesAnthelminticsharmonine

Identifiers

PMID30870428
PMCPMC6436750
OpenAlexW2921931377

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 OpenQuestion graph.