Toxicity Mechanism of Artesunate-Induced Cardiotoxic Injury:Based on Network Toxicology and Serum Metabolomics
- VernacularTitle:基于网络毒理学和代谢组学的青蒿琥酯心脏毒性作用机制研究
- Author:
Lulu CHEN
1
;
Zhenshuang YUAN
;
Jie LIU
;
Yujin MA
;
Tao JIANG
;
Ying LI
;
Hongwei JIANG
Author Information
- Keywords: Artesunate; Metabolomics; Cardiotoxicity; Network toxicology; Target protein
- From: World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(12):3808-3828
- CountryChina
- Language:Chinese
- Abstract: Objective This study aimed to investigate the mechanism of artesunate-induced cardiotoxicity by using network toxicology and serum untargeted metabolomics.Methods The key targets and signaling pathways of artesunate-induced cardiotoxicity were expored by network toxicology technique.The toxic effect of artesunate on Healthy C57BL/6J mice was evaluated according to the pathological morphology of the heart and the levels of serum biochemical indexes included LDH and CKMB.Serum untargeted metabolomics analysis was combined with multivariate statistical analysis to search the key endogenous metabolites of artesunate cardiotoxic injury and related metabolic pathways.Results 64 targets including AKT1,EGFR,CASP3,VEGFA and 165 signaling pathways including Apoptosis,PI3K-Akt,FoxO were screened out by network toxicology,.Serum metabolomics analysis identified the serum metabolites affected by artesunate-induced cardiotoxicity included lysophosphatidylcholine,lysophosphatidylethanolamine,indoleacetaldehyde,etc.The results of metabolic pathways enrichment analysis were glycerophosphatidylcholine metabolism and tryptophan metabolism.Conclusion Artesunate 600 mg·kg-1 can induce cardiotoxicity in C57BL/6J mice after 1-week administration,and the mechanism is related to glycerophosphatidylcholine metabolism disorder and tryptophan metabolism disorder.This study provides a reference for the early prediction and evaluation of artesunate induced drug-induced cardiotoxicity.
