Investigation of the reverse effect of Danhong injection on doxorubicin-induced cardiotoxicity in H9c2 cells: Insight by LC–MS based non-targeted metabolomic analysis

Xiaojiao Yi, Junfeng Zhu, Jinghui Zhang, Yun Gao, Zhongjian Chen, Shihai Lu, Zongwei CAI, Yanjun HONG*, Yongjiang Wu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Although Danhong injection (DHI) has been clearly shown to attenuate ischemic myocardial injury and improve heart function, there is no research regarding its role in doxorubicin (DOX)-induced cardiomyopathy. In this study, we aimed to investigate the reverse effect of DHI on DOX-induced cardiotoxicity in H9c2 cells. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay demonstrated that DHI had no cytotoxicity towards the relevant cell line unless the concentration was as high as 50 μL/mL. The satisfactory cardioprotective effect of DHI exerted at the concentration of 10 μL/mL, which agreed well with the result of real-time cell viability assay. Then non-targeted metabolomics based on LC–MS was employed to characterize metabolic alterations in DOX-induced cells with DHI treatment. Multivariate analysis, including PCA and PLS-DA, revealed 31 altered metabolites after DOX treatment that were primarily related to the disturbance of amino acids and nucleotides metabolism. While DHI could intervene in some disturbed metabolic pathways, such as the metabolism of arginine, glutathione (GSH), pantothenic acid, cytidine, inosine and 5′-methylthioadenosine. These results suggested that DHI exerted the therapeutic effect by improving energy metabolism and attenuating oxidative stress. The present study can lay a foundation for further research on the promising therapeutic effect of DHI in managing DOX-induced cardiotoxicity.

Original languageEnglish
Pages (from-to)264-270
Number of pages7
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume152
DOIs
Publication statusPublished - 15 Apr 2018

Scopus Subject Areas

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry

User-Defined Keywords

  • Cardiotoxicity
  • Danhong injection
  • Doxorubicin
  • Non-targeted metabolomics
  • UHPLC-Q-Exactive MS

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