Therapeutic effects of Aconiti Lateralis Radix Praeparata combined with Zingiberis Rhizoma on doxorubicin-induced chronic heart failure in rats based on an integrated approach.

Abstract

OBJECTIVES:

This study was aimed to explore the mechanism of Aconiti Lateralis Radix Praeparata (ALRP) and Zingiberis Rhizoma (ZR) on doxorubicin (DOX)-induced chronic heart failure (CHF) in rats by integrated approaches.

METHODS:

Effects of ALRP and ZR on cardiac function, serum biochemical indicators and histopathology in rats were analysed. Moreover, UHPLC-Q-TOF/MS was performed to identify the potential metabolites affecting the pathological process of CHF. Metabolomics and network pharmacology analyses were conducted to illustrate the possible pathways and network in CHF treatment. The predicted gene expression levels in heart tissue were verified and assessed by RT-PCR.

KEY FINDINGS:

ALRP-ZR demonstrated remarkable promotion of hemodynamic indices and alleviated histological damage of heart tissue. Metabolomics analyses showed that the therapeutic effect of ALRP and ZR is mainly associated with the regulation of eight metabolites and ten pathways, which may be responsible for the therapeutic efficacy of ALRP-ZR. Moreover, the results of RT-PCR showed that ALRP-ZR could substantially increase the expression level of energy metabolism-related genes, including PPARδ, PPARγ, Lpl, Scd, Fasn and Pla2g2e.

CONCLUSIONS:

The results highlighted the role of ALRP-ZR in the treatment of CHF by influencing the metabolites related to energy metabolism pathway via metabolomics and network pharmacology analyses.

• Authors: Jian-Xia Wen, Rui-Sheng Li, Jian Wang, Jun-Jie Hao, Wei-Han Qin, Tao Yang, Rui-Lin Wang, Shi-Zhang Wei, Xiao-Yi Liu, Hao-Tian Li, Jia-Bo Wang, Hong-Hong Liu, Yan-Ling Zhao
• Journal: The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 72 Issue 2 Pg. 279-293 (Feb 2020) ISSN: 2042-7158 [Electronic] England
• PMID: 31743450 (Publication Type: Journal Article)
• Copyright: © 2019 Royal Pharmaceutical Society.

Chemical References

• Plant Extracts
• Doxorubicin

Topics

• Aconitum (chemistry)
• Animals
• Doxorubicin (toxicity)
• Energy Metabolism (drug effects)
• Gene Expression Regulation
• Zingiber officinale (chemistry)
• Heart Failure (chemically induced, drug therapy, genetics)
• Male
• Metabolomics
• Plant Extracts (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Reverse Transcriptase Polymerase Chain Reaction
• Rhizome