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.

The objective of this study was to understand the effect of long-term aconitine (AC) oral administration on the digestive tract and serum metabolism. Subjects consumed either 0.9% NaCl (n = 8) or AC (n = 17) gavage designed to represent human chronic AC administrations for 13 days. Organ pathology was determined using hematoxylin-eosin staining and immunohistochemistry. Fecal and proximal intestinal content samples were collected to perform shotgun metagenomic sequencing. Serum samples were collected, and untargeted metabolomics was performed. In this study, AC administration induced proximal intestine, liver, and kidney injury. Microbiome composition remained stable after AC exposure, while several microbes presented dynamic alteration. Moreover, AC affected the abundance of the fatty acid biosynthesis rate-limiting gene accA at day 7. AC induces 30 serum metabolites to significantly change at day 14, including several short-chain acylcarnitines. WGCNA revealed 2 sub-modules associated with the level of several short-chain acylcarnitines. In summary, AC affects the digestive tract and serum metabolism after chronic administration. AC may affect the enrichment of microbial-derived accA gene. The abundance of serum acylcarnitines detected in the AC group may associate with its anti-heart failure effects.