Metabolic exploration of the developmental abnormalities and neurotoxicity of Esculentoside B, the main toxic factor in Phytolaccae radix

• Published in: Food and chemical toxicology 2023-06, Vol.176, p.113777-113777, Article 113777
• Main Authors: Ren, Sipei, Zhang, Zhichao, Song, Qinyang, Ren, Zhaoyang, Xiao, Jian, Li, Luqi, Zhang, Qiang
• Format: Article
• Language: English
• Subjects: Animals; Carboxylic Acids; Embryo, Nonmammalian; Larva; Water Pollutants, Chemical - metabolism; Zebrafish
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2023.113777

radix is a perennial herb, and its extracts have various biological properties that make it a potential candidate for the treatment of tumors, edema, and lymphatic stasis. However, the main factor contributing to its toxicity are not clear. Here, we used a zebrafish toxicological model to study the main toxicity factor of P. radix and explore the potential mechanisms involved. The results revealed that Esculentoside B was the major toxic factor of P. radix. Exposure of zebrafish larvae to Esculentoside B caused developmental abnormalities, neurotoxicity and altered locomotor behavior. The combination of AChE activity and the expression levels of genes relevant to CNS development demonstrated that Esculentoside B is neurotoxic to zebrafish larvae, impairs their CNS development, and that AChE may be a toxic target of Esculentoside B. Metabolomic analysis has revealed that Esculentoside B exposure can disrupt D-Amino acid metabolism, protein export, autophagy, and mTOR signaling pathways in zebrafish larvae. These findings provide insights into the molecular mechanisms underlying EsB-induced neurotoxicity in zebrafish, which can facilitate further research and development of P. radix for safe consumption. [Display omitted] •Esculentoside B was the main toxic components of P. radix.•Esculentoside B causes abnormal development and neurotoxicity in zebrafish larvae.•Esculentoside B causes metabolite disruption in zebrafish larvae.