4.5 Article

An in silico insight on the mechanistic aspects of gelsenicine toxicity: A reverse screening study pointing to the possible involvement of acetylcholine binding receptor

Journal

TOXICOLOGY LETTERS
Volume 386, Issue -, Pages 1-8

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2023.09.003

Keywords

Gelsenicine; Toxicodynamics; Target fishing; in silico toxicology; Acetylcholine receptor; Alkaloids

Categories

Ask authors/readers for more resources

Gelsedine-type alkaloids are highly toxic plant secondary metabolites produced by shrubs belonging to the Gelsemium genus. Gelsenicine is one of the most concerning gelsedine-type alkaloids with a lethal dose lower than 1 mg/Kg in mice. Several reported episodes of poisoning in livestock and fatality cases in humans due to the usage of Gelsemium plants extracts were reported. Also, gelsedine-type alkaloids were found in honey constituting a potential food safety issue. However, their toxicological understanding is scarce and the molecular mechanism underpinning their toxicity needs further investigations.
Gelsedine-type alkaloids are highly toxic plant secondary metabolites produced by shrubs belonging to the Gelsemium genus. Gelsenicine is one of the most concerning gelsedine-type alkaloids with a lethal dose lower than 1 mg/Kg in mice. Several reported episodes of poisoning in livestock and fatality cases in humans due to the usage of Gelsemium plants extracts were reported. Also, gelsedine-type alkaloids were found in honey constituting a potential food safety issue. However, their toxicological understanding is scarce and the molecular mechanism underpinning their toxicity needs further investigations. In this context, an in silico approach based on reverse screening, docking and molecular dynamics successfully identified a possible gelsenicine biological target shedding light on its toxicodynamics. In line with the available crystallographic data, it emerged gelsenicine could target the acetylcholine binding protein possibly acting as a partial agonist against alpha 7 nicotinic acetyl-choline receptor (AChR). Overall, these results agreed with evidence previously reported and prioritized AChR for further dedicated analysis.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.5
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available