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

ABSTRACT

P 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.