The toxic components, toxicological mechanism and effective antidote for Gelsemium elegans poisoning.
10.1016/j.apsb.2025.07.016
- Author:
Niping LI
1
;
Yaorong YANG
1
;
Shengyuan ZHANG
2
;
Bin JIANG
3
;
Wei ZHANG
1
;
Haibo WANG
4
;
Lixin CHEN
4
;
Liwei WANG
4
;
Yiyi LI
1
;
Lei SHI
1
;
Wencai YE
1
;
Lei WANG
1
Author Information
1. State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou 510632, China.
2. Center for Bioactive Natural Molecules and Innovative Drugs Research, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China.
3. Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
4. Department of Pharmacology, Medical College, Jinan University, Guangzhou 510632, China.
- Publication Type:Journal Article
- Keywords:
Alkaloids;
Antidote;
GABAA receptor;
Gelsemium elegans poisoning;
Respiratory failure;
Structure–toxicity relationship;
Toxic components;
Toxicological mechanism
- From:
Acta Pharmaceutica Sinica B
2025;15(9):4872-4885
- CountryChina
- Language:English
-
Abstract:
Gelsemium elegans (G. elegans) is an extremely poisonous plant that is widely distributed in southern China and southeastern Asia. G. elegans poisoning events occur frequently in southern China, and are therefore an urgent public health problem requiring multidisciplinary action. However, the toxic components and toxicological mechanisms remain unclear. Here, we describe a systematic investigation on the toxic components of G. elegans, resulting in the isolation and identification of 120 alkaloids. Based on acute toxicity screening, the structure-toxicity relationship of Gelsemium alkaloids was proposed for the first time. Moreover, gelsedine- and humantenine-type alkaloids were detected in the clinical blood sample, and were confirmed to be causative in the poisoning. The most toxic compound, gelsenicine (1), had selective inhibitory effects toward ventral respiratory group (VRG) neurons in the medulla, which is the main brain region controlling respiration in the central nervous system. Gelsenicine (1) strongly inhibited the firing of action potentials in VRG neurons through its ability to stimulate GABAA receptors, the main receptors involved in inhibitory neurotransmission. Application of GABAA receptor antagonists successively reversed action potential firing in gelsenicine (1)-treated VRG neurons. Importantly, the GABAA receptor antagonists securinine and flumazenil significantly increased the survival of poisoned animals. Our findings provide insight into the components and mechanisms of G. elegans toxicity, and should assist the development of effective emergency treatments for G. elegans poisoning.
