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

  • Food Chem Toxicol. 2023 Jun:176:113777. doi: 10.1016/j.fct.2023.113777.
Sipei Ren  1 ,  Zhichao Zhang  1 ,  Qinyang Song  1 ,  Zhaoyang Ren  1 ,  Jian Xiao  2 ,  Luqi Li  3 ,  Qiang Zhang  4
Affiliations
  • 1. Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, 712100, Shanxi, China.
  • 2. Shaanxi Key Laboratory of Phytochemistry, College of Chemistry and Chemical Engineering, Baoji University of Arts and Sciences, Baoji, 721013, China. Electronic address: [email protected].
  • 3. Life Science Research Core Services, Northwest A&F University, Yangling, Xianyang, 712100, China.
  • 4. Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, 712100, Shanxi, China; Shaanxi Key Laboratory of Phytochemistry, College of Chemistry and Chemical Engineering, Baoji University of Arts and Sciences, Baoji, 721013, China. Electronic address: [email protected].
PMID: 37080526 DOI: 10.1016/j.fct.2023.113777
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.

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