Decomposing the Mechanism of Qishen Granules in the Treatment of Heart Failure by a Quantitative Pathway Analysis Method

Molecules. 2018 Jul 23;23(7):1829. doi: 10.3390/molecules23071829.

Abstract

Qishen granules (QSG) have beneficial therapeutic effects for heart failure, but the effects of decomposed recipes, including Wenyang Yiqi Huoxue (WYH) and Qingre Jiedu (QJ), are not clear. In this study, the efficacy of WYH and QJ on heart failure is evaluated by using transverse aortic constriction (TAC) induced mice and the significantly changed genes in heart tissues were screened with a DNA array. Furthermore, a new quantitative pathway analysis tool is developed to evaluate the differences of pathways in different groups and to identify the pharmacological contributions of the decomposed recipes. Finally, the related genes in the significantly changed pathways are verified by a real-time polymerase chain reaction and a Western blot. Our data show that both QJ and WYH improve the left ventricular ejection fraction, which explain their contributions to protect against heart failure. In the energy metabolism, QJ achieves the therapeutic effects of QSG through nicotinamide nucleotide transhydrogenase (Nnt)-mediated mechanisms. In ventricular remodeling and inflammation reactions, QJ and WYH undertake the therapeutic effects through 5'-nucleotidase ecto (Nt5e)-mediated mechanisms. Together, QJ and WYH constitute the therapeutic effects of QSG and play important roles in myocardial energy metabolism and inflammation, which can exert therapeutic effects for heart failure.

Keywords: Qingre Jiedu; Qishen granules; Wenyang Yiqi Huoxue; decomposing formula; heart failure; quantitative pathway analysis.

MeSH terms

  • Animals
  • Biomarkers
  • Disease Models, Animal
  • Drugs, Chinese Herbal / chemistry*
  • Drugs, Chinese Herbal / pharmacology*
  • Echocardiography
  • Energy Metabolism / drug effects*
  • Gene Expression Regulation / drug effects
  • Heart Failure / diagnosis
  • Heart Failure / drug therapy
  • Heart Failure / metabolism*
  • Heart Failure / physiopathology
  • Hypertrophy, Left Ventricular / diagnosis
  • Hypertrophy, Left Ventricular / drug therapy
  • Hypertrophy, Left Ventricular / etiology
  • Hypertrophy, Left Ventricular / physiopathology
  • Metabolic Networks and Pathways / drug effects*
  • Mice
  • Transcriptome
  • Ventricular Dysfunction, Left / drug therapy
  • Ventricular Dysfunction, Left / metabolism
  • Ventricular Dysfunction, Left / physiopathology
  • Ventricular Remodeling

Substances

  • Biomarkers
  • Drugs, Chinese Herbal