Gelsenicine as an emerging foodborne hazard: phytochemistry, pharmacokinetics, and mechanistic toxicology in a systems framework

Gelsenicine is the most toxic indole alkaloid in Gelsemium elegans Benth. (G. elegans). Poisoning associated with this plant is frequent and poses a significant concern for food safety and public health. Human exposure occurs through accidental ingestion, plant misidentification during collection or purchase, contaminated foods, and indirect intake via honey. Different plant parts resemble commonly used medicinal or edible species, which increases the risk of unintentional consumption. Although low doses of gelsenicine exhibit pharmacological effects, its narrow therapeutic window and potent neurotoxicity make safe intake highly challenging. This review provides a food safety-focused summary of gelsenicine, covering its phytochemical origin, structural characteristics, and pharmacokinetics. Gelsenicine is rapidly absorbed, extensively distributed in the central nervous system, exhibits low oral bioavailability, and is metabolized predominantly via N-demethylation. Major exposure pathways related to plant misidentification, clinical features of poisoning, and toxicological evidence for risk classification are systematically reviewed. Mechanistically, we integrate in vivo, in vitro, and multi-omics data to propose a multi-target toxicity network model that includes calcium overload, excitotoxicity, neurotransmitter dysregulation, impaired energy metabolism, and respiratory center depression. This model provides a coherent link between molecular initiating events and systemic toxicity. Potential mitigation and detoxification strategies based on these mechanisms are also discussed. Future priorities include developing predictive, mechanism-based risk assessment frameworks using integrated systems toxicology, identifying early diagnostic biomarkers for rapid screening, and targeted interventions at key toxicity nodes. Collectively, these insights aim to support proactive prevention, rapid diagnosis, and risk-based management of gelsenicine poisoning, thereby enhancing food safety.