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Toxic Effects of Koumine on the Early-Life Development Stage of Zebrafish

Koumine is one of the most abundant alkaloids found in Gelsemium elegans, and it has a wide range of pharmacological effects including antitumor, anti-inflammatory, analgesic treatment effects, and antianxiety. However, its high toxicity and unclear mechanism of action have greatly limited the medic...

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Autores principales: Wang, Dongjie, Leng, Xinyi, Tian, Yao, Liu, Jiangdong, Zou, Jixing, Xie, Shaolin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10611223/
https://www.ncbi.nlm.nih.gov/pubmed/37888703
http://dx.doi.org/10.3390/toxics11100853
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author Wang, Dongjie
Leng, Xinyi
Tian, Yao
Liu, Jiangdong
Zou, Jixing
Xie, Shaolin
author_facet Wang, Dongjie
Leng, Xinyi
Tian, Yao
Liu, Jiangdong
Zou, Jixing
Xie, Shaolin
author_sort Wang, Dongjie
collection PubMed
description Koumine is one of the most abundant alkaloids found in Gelsemium elegans, and it has a wide range of pharmacological effects including antitumor, anti-inflammatory, analgesic treatment effects, and antianxiety. However, its high toxicity and unclear mechanism of action have greatly limited the medicinal development and use of koumine. We investigated the toxic effects of koumine on the developmental toxicity and behavioral neurotoxicity of zebrafish embryos and larvae. Embryos at 6 h postfertilization (hpf) were exposed to 12.5, 25, 50, 75, and 100 mg/L of koumine until 120 hpf. Koumine affected the hatching and heartbeats of the embryos. The morphological analysis also revealed many abnormalities, such as shortened bodies, yolk sac edemas, tail malformations, and pericardial edemas. To identify the neurotoxicity of koumine, the behavior of the larvae was measured. Koumine at 50 and 100 mg/L affect the escape response. The embryos exhibited uncoordinated muscle contractions along the body axis in response to touch at 36 hpf. More importantly, we found that the neurotoxicity of koumine is mainly caused by influencing the ACh content and the activity of AChE without impairing motor neuron development. A comprehensive analysis shows that a high concentration of koumine has obvious toxic effects on zebrafish, and the safe concentration of koumine for zebrafish should be less than 25 mg/L. These results will be valuable for better understanding the toxicity of koumine and provide new insights into the application of koumine.
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spelling pubmed-106112232023-10-28 Toxic Effects of Koumine on the Early-Life Development Stage of Zebrafish Wang, Dongjie Leng, Xinyi Tian, Yao Liu, Jiangdong Zou, Jixing Xie, Shaolin Toxics Article Koumine is one of the most abundant alkaloids found in Gelsemium elegans, and it has a wide range of pharmacological effects including antitumor, anti-inflammatory, analgesic treatment effects, and antianxiety. However, its high toxicity and unclear mechanism of action have greatly limited the medicinal development and use of koumine. We investigated the toxic effects of koumine on the developmental toxicity and behavioral neurotoxicity of zebrafish embryos and larvae. Embryos at 6 h postfertilization (hpf) were exposed to 12.5, 25, 50, 75, and 100 mg/L of koumine until 120 hpf. Koumine affected the hatching and heartbeats of the embryos. The morphological analysis also revealed many abnormalities, such as shortened bodies, yolk sac edemas, tail malformations, and pericardial edemas. To identify the neurotoxicity of koumine, the behavior of the larvae was measured. Koumine at 50 and 100 mg/L affect the escape response. The embryos exhibited uncoordinated muscle contractions along the body axis in response to touch at 36 hpf. More importantly, we found that the neurotoxicity of koumine is mainly caused by influencing the ACh content and the activity of AChE without impairing motor neuron development. A comprehensive analysis shows that a high concentration of koumine has obvious toxic effects on zebrafish, and the safe concentration of koumine for zebrafish should be less than 25 mg/L. These results will be valuable for better understanding the toxicity of koumine and provide new insights into the application of koumine. MDPI 2023-10-12 /pmc/articles/PMC10611223/ /pubmed/37888703 http://dx.doi.org/10.3390/toxics11100853 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Dongjie
Leng, Xinyi
Tian, Yao
Liu, Jiangdong
Zou, Jixing
Xie, Shaolin
Toxic Effects of Koumine on the Early-Life Development Stage of Zebrafish
title Toxic Effects of Koumine on the Early-Life Development Stage of Zebrafish
title_full Toxic Effects of Koumine on the Early-Life Development Stage of Zebrafish
title_fullStr Toxic Effects of Koumine on the Early-Life Development Stage of Zebrafish
title_full_unstemmed Toxic Effects of Koumine on the Early-Life Development Stage of Zebrafish
title_short Toxic Effects of Koumine on the Early-Life Development Stage of Zebrafish
title_sort toxic effects of koumine on the early-life development stage of zebrafish
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10611223/
https://www.ncbi.nlm.nih.gov/pubmed/37888703
http://dx.doi.org/10.3390/toxics11100853
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