Experimental and Computational Investigation of the Target and Mechanisms of Gelsemium Alkaloids in the Central Nervous System

Wang, Yunfan; Yang, Zhijiang; Huang, Tengxin; Pan, Li; Ding, Junjie; Liu, Zhaoying

doi:10.3390/ijms26031312

Open AccessArticle

Experimental and Computational Investigation of the Target and Mechanisms of Gelsemium Alkaloids in the Central Nervous System

by

Yunfan Wang

¹,

Zhijiang Yang

²,

Tengxin Huang

²,

Li Pan

²,

Junjie Ding

^2,* and

Zhaoying Liu

^1,*

¹

College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China

²

State Key Laboratory of NBC Protection for Civilian, Beijing 102205, China

^*

Authors to whom correspondence should be addressed.

Int. J. Mol. Sci. 2025, 26(3), 1312; https://doi.org/10.3390/ijms26031312

Submission received: 18 December 2024 / Revised: 23 January 2025 / Accepted: 31 January 2025 / Published: 4 February 2025

(This article belongs to the Special Issue Molecular Studies of Natural Compounds and Plant Extracts—3rd Edition)

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Abstract

Gelsemium has a long history of medicinal use but is also a poisonous plant. Some low-toxicity alkaloids in Gelsemium exhibit anxiolytic, anti-inflammatory, analgesic, and other pharmacological effects; however, certain alkaloids in Gelsemium are highly toxic. Nevertheless, the molecular targets underlying the biological effects of Gelsemium alkaloids remain poorly understood. We employed electrophysiological techniques and molecular modeling to examine the modulatory effects of Gelsemium alkaloids on inhibitory neurotransmitter receptors, as well as to elucidate the mechanisms underlying their molecular interactions. Our findings indicate that low-toxicity alkaloids primarily exert their pharmacological effects through actions on glycine receptors, with the binding site located at the orthosteric site between two α-subunits. Both highly toxic and low-toxicity alkaloids target GABAA receptors, using the β+/α− interface transmembrane structural domains as common binding sites. These results identify the targets through which Gelsemium alkaloids affect the central nervous system and predict the binding modes and key amino acids involved from a computational modeling perspective. However, further experimental validation through mutational studies is necessary to strengthen these findings.

Keywords: Gelsemium alkaloids; GABAA receptor; glycine receptor; electrophysiology; molecular dynamics simulation

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MDPI and ACS Style

Wang, Y.; Yang, Z.; Huang, T.; Pan, L.; Ding, J.; Liu, Z. Experimental and Computational Investigation of the Target and Mechanisms of Gelsemium Alkaloids in the Central Nervous System. Int. J. Mol. Sci. 2025, 26, 1312. https://doi.org/10.3390/ijms26031312

AMA Style

Wang Y, Yang Z, Huang T, Pan L, Ding J, Liu Z. Experimental and Computational Investigation of the Target and Mechanisms of Gelsemium Alkaloids in the Central Nervous System. International Journal of Molecular Sciences. 2025; 26(3):1312. https://doi.org/10.3390/ijms26031312

Chicago/Turabian Style

Wang, Yunfan, Zhijiang Yang, Tengxin Huang, Li Pan, Junjie Ding, and Zhaoying Liu. 2025. "Experimental and Computational Investigation of the Target and Mechanisms of Gelsemium Alkaloids in the Central Nervous System" International Journal of Molecular Sciences 26, no. 3: 1312. https://doi.org/10.3390/ijms26031312

APA Style

Wang, Y., Yang, Z., Huang, T., Pan, L., Ding, J., & Liu, Z. (2025). Experimental and Computational Investigation of the Target and Mechanisms of Gelsemium Alkaloids in the Central Nervous System. International Journal of Molecular Sciences, 26(3), 1312. https://doi.org/10.3390/ijms26031312

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Experimental and Computational Investigation of the Target and Mechanisms of Gelsemium Alkaloids in the Central Nervous System

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