Academic Journal
Insects in anthelminthics research: Lady beetle-derived harmonine affects survival, reproduction and stem cell proliferation of Schistosoma mansoni.
| العنوان: | Insects in anthelminthics research: Lady beetle-derived harmonine affects survival, reproduction and stem cell proliferation of Schistosoma mansoni. |
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| المؤلفون: | Josina Kellershohn, Laura Thomas, Steffen R Hahnel, Arnold Grünweller, Roland K Hartmann, Martin Hardt, Andreas Vilcinskas, Christoph G Grevelding, Simone Haeberlein |
| المصدر: | PLoS Neglected Tropical Diseases, Vol 13, Iss 3, p e0007240 (2019) |
| بيانات النشر: | Public Library of Science (PLoS), 2019. |
| سنة النشر: | 2019 |
| المجموعة: | LCC:Arctic medicine. Tropical medicine LCC:Public aspects of medicine |
| مصطلحات موضوعية: | Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270 |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1935-2727 1935-2735 |
| Relation: | http://europepmc.org/articles/PMC6436750?pdf=render; https://doaj.org/toc/1935-2727; https://doaj.org/toc/1935-2735 |
| DOI: | 10.1371/journal.pntd.0007240 |
| URL الوصول: | https://doaj.org/article/2ae045f16f1c47d5ad3ce0513e22e9cc |
| رقم الانضمام: | edsdoj.2ae045f16f1c47d5ad3ce0513e22e9cc |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 19352727 19352735 |
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| DOI: | 10.1371/journal.pntd.0007240 |