Evidence map›Paper›PMID 38256913›Full record

ArticlePharmaceuticals (Basel, Switzerland)2024

Identification of Antagonistic Action of Pyrrolizidine Alkaloids in Muscarinic Acetylcholine Receptor M1 by Computational Target Prediction Analysis.

Sara Abdalfattah, Caroline Knorz, Akhtar Ayoobi, Ejlal A Omer, Matteo Rosellini, Max Riedl, Christian Meesters, Thomas Efferth

Open access · goldAbstract read
In one paragraph

Article in Pharmaceuticals (Basel, Switzerland), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 18% 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

5 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.

  1. Molecules (Basel, Switzerland) · 2026
    Pooled it
  2. Review
  3. Article
  4. Investigation of Anticancer Peptides Derived fromMolecules (Basel, Switzerland) · 2025
    Article
  5. 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

8 authors at 3 institutions in 2 countries.

Sara AbdalfattahDepartment of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.ORCID 0000-0002-9186-2516
Caroline KnorzDepartment of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.
Akhtar AyoobiDepartment of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.ORCID 0000-0001-7942-804X
Ejlal A OmerDepartment of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.
Matteo RoselliniDepartment of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.
Max RiedlInstitute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, 04107 Leipzig, Germany.
Christian MeestersHigh Performance Computing Group, University of Mainz, 55131 Mainz, Germany.
Thomas EfferthDepartment of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.ORCID 0000-0002-2637-1681
Johannes Gutenberg University Mainz · DELeipzig University · DEUniversity of Applied Sciences Mainz · DE

Funding

Ministry of Social Affairs,Labor, Health and Demography, Rheinland-Pfalz, Germany. PoUvPA 633-2
6 · The paper itself

Abstract

Pyrrolizidine alkaloids (PAs) are one of the largest distributed classes of toxins in nature. They have a wide range of toxicity, such as hepatotoxicity, pulmonary toxicity, neuronal toxicity, and carcinogenesis. Yet, biological targets responsible for these effects are not well addressed. Using methods of computational biology for target identification, we tested more than 200 PAs. We used a machine-learning approach that applies structural similarity for target identification, ChemMapper, and SwissTargetPrediction. The predicted target with high probability was muscarinic acetylcholine receptor M1. The predicted interactions between this target and PAs were further studied by molecular docking-based binding energies using AutoDock and VinaLC, which revealed good binding affinities. The PAs are bound to the same binding pocket as pirenzepine, a known M1 antagonist. These results were confirmed by in vitro assays showing that PAs increased the levels of intracellular calcium. We conclude that PAs are potential acetylcholine receptor M1 antagonists. This elucidates for the first time the serious neuro-oncological toxicities exerted by PA consumption.

Indexed as

alkaloidscomputational biologyherbal medicinenatural productsneurotoxicityphytotherapyvirtual drug screening

Identifiers

PMID38256913
PMCPMC10818892
OpenAlexW4390672761

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.