The primary neurotoxic factor, Lansamide I, from Clausena lansium fruits and metabolic dysfunction invoked

Abstract

Wampee (Clausena lansium) is a common fruit in South Asia. The pulp is a tasty food, and the seed is a typical traditional herb in China. However, we identified a primary toxic compound, Lansamide I, by NMR and X-ray diffraction of single-crystal. The compound occurred at 4.17 ± 0.16 mg/kg of dried seed and 0.08 ± 0.01 g/kg of fresh fruit. In our phenotype-based toxicity investigation, the compound caused decreased hatchability of zebrafish eggs, increased malformations such as enlarged yolk sacs and pericardial edema, and delayed body length development. Moreover, the compound also caused nerve cell damage and decreased locomotor activity. The compound caused an increase in peroxidation levels in vivo, with increases in both malondialdehyde and superoxide dismutase levels, but did not interfere with acetylcholinesterase levels. Metabolomic studies found that the compound caused significant up-regulation of 16 metabolites, mainly amino acids and peptides, which were involved in the nucleotide metabolism pathway and the betaine biosynthesis module. The qRT-PCR revealed that the substance interfered with the mRNA expression of tat and dctpp. These discoveries offer fresh perspectives on the toxicity mechanisms and metabolic response to the primary harmful molecules in wampee, which could inform the rational usage of wampee resources.