# Untargeted Metabolomic Analysis Using UPLC–MS/MS Reveals Metabolic Changes Associated With Lanmaoa asiatica Poisoning

## TL;DR

This study uses advanced metabolomic techniques to uncover how Lanmaoa asiatica poisoning affects metabolism, particularly through mitochondrial dysfunction and addiction-related pathways.

## Contribution

First use of UPLC–MS/MS non-targeted metabolomics to analyze Lanmaoa asiatica poisoning and identify potential biomarkers.

## Key findings

- 914 differential metabolites were identified, including upregulated 5-methoxytryptophan and protocatechuic acid.
- Disturbances in oxidative phosphorylation and morphine addiction pathways were observed.
- Adenosine derivatives showed high diagnostic potential as biomarkers.

## Abstract

Lanmaoa asiatica is known for its unique flavor; however, improper consumption can induce severe neuropsychiatric symptoms, including hallucinations and irritability. The underlying toxicity mechanism remains unclear, and the lack of specific antidotes poses a significant threat to patient safety. This study employed ultra‐high performance liquid chromatography–tandem mass spectrometry (UPLC‐MS/MS) to analyze the plasma metabolic profiles of patients with Lanmaoa asiatica poisoning and healthy controls. A total of 20 patients were included, with an average age of 36.9 ± 13.08 years. No significant differences were observed in age, gender, or laboratory indicators between the patient and control groups (p > 0.05). Poisoned patients primarily exhibited neuropsychiatric symptoms, including hallucinations (75%) and general weakness (60%), along with gastrointestinal symptoms such as nausea (60%) and vomiting (45%). Metabolomic analysis identified 914 differential metabolites, primarily involving benzene derivatives, organic acids and their derivatives, amino acid metabolites, and heterocyclic compounds. Notably, 5‐methoxytryptophan (5‐MTP) and protocatechuic acid were significantly upregulated, suggesting potential pharmacological relevance. KEGG pathway analysis revealed disturbances in oxidative phosphorylation and the morphine addiction pathway, implicating mitochondrial dysfunction as a key factor in Lanmaoa asiatica toxicity. Additionally, adenosine monophosphate (AUC = 0.917), adenosine 5′‐diphosphate (AUC = 0.935), and adenosine 5′‐triphosphate (AUC = 0.895) were identified as potential metabolic biomarkers and therapeutic targets. Despite the overall favorable prognosis and no significant damage to vital organs such as the liver and kidneys, the severe hallucinogenic effects raise concerns about increased risks of self‐harm and accidental injury. However, this study has certain limitations, including a relatively small sample size and potential challenges in metabolite identification inherent to untargeted metabolomics. These factors may affect the generalizability and biological interpretation of the findings. Future studies with larger cohorts and integrated, targeted approaches are warranted to validate and refine these results.

Lanmaoa asiatica possesses notable nutritional and pharmacological value, yet its potential to cause neuropsychiatric symptoms remains unclear. This study represents the first application of UPLC‐MS/MS non‐targeted metabolomics technology to systematically analyze the plasma metabolic profiles of patients with Lanmaoa asiatica poisoning, particularly involving mitochondrial dysfunction and morphine addiction pathways. Key metabolites such as 5‐methoxytryptophan and adenosine derivatives may be identified as potential biomarkers. However, the small sample size and limitations of untargeted metabolomics may affect the generalizability and interpretation of the results.