Investigating the Mechanism of Action of Schisandra chinensis Combined with Coenzyme Q10 in the Treatment of Heart Failure Based on PI3K-AKT Pathway

Drug Des Devel Ther. 2023 Mar 27:17:939-957. doi: 10.2147/DDDT.S393995. eCollection 2023.

Abstract

Purpose: To study the active components, drug targets and mechanism of Schisandra chinensis (S.chinensis) combined with coenzyme Q10 (CQ10) in the treatment of heart failure (HF).

Methods: Network pharmacology combined with the gene expression omnibus chip method to analyze the main pathways by which S.chinensis combined with CQ10 functioned to treat heart failure. Subsequently, the biological activities of the major pathway key proteins and their corresponding compounds were verified by molecular docking techniques. Finally, the molecular mechanism of S. chinensis combined with CQ10 for the treatment of heart failure was verified using a rat heart failure model induced by isoproterenol hydrochloride and using hematoxylin-eosin staining, TUNEL, immunohistochemistry and Western blot.

Results: Network pharmacology combined with experimental validation suggests that the mechanism of action of S.chinensis combined with CQ10 in the treatment of heart failure may involve CQ10, Citral, Schisandrone, Schisanhenol B, Gomisin O, Schisandrin C and other components, which may synergistically inhibit the PI3K-AKT signaling pathway and affect the expression of AKT1, PIK3CG and other targets on this pathway. In addition, S. chinensis combined with CQ10 could effectively improve the cardiac coefficients of rats with heart failure, reduce the area of myocardial fibrosis and lowered the serum levels of IL-1β and TNF-α in heart failure rats, as well as reduced cardiac myocyte apoptosis, increased Bcl-2 expression and decreased p-PI3K/PI3K, p-AKT/AKT, P65 and Bax expression in cardiac tissue. Comparison of the results showed that the combination of S.chinensis and CQ10 was more effective compared with CQ10 alone, ie, the ability of S.chinensis combined with CQ10 in improving cardiac function, inhibiting cardiomyocyte apoptosis and reducing inflammatory response lies in the synergistic effect of PI3K/AKT signaling pathway.

Conclusion: The therapeutic effect of S.chinensis combined with CQ10 on heart failure, which may occur through the inhibition of PI3K/AKT signaling pathway.

Keywords: Schisandra chinensis; coenzyme Q10; heart failure; mechanism validation; molecular docking; network pharmacology.

MeSH terms

  • Animals
  • Drugs, Chinese Herbal* / pharmacology
  • Heart Failure* / drug therapy
  • Molecular Docking Simulation
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Schisandra* / chemistry

Substances

  • coenzyme Q10
  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • Drugs, Chinese Herbal

Grants and funding

This work was supported by the Engineering Technology Research Center. Research and Application Demonstration of Key Technologies for the Industry of Chinese Herbs such as Tianma and Panax notoginseng in Southwest China (2021YFD1601000), Shaanxi Province, supported by the Engineering and Technology Research Center for the Application and Development of Chinese Herbs in Qinling. Research on comprehensive development and utilization of medicinal herbs of “Wu Wei Zi” of Qin Medicine (2021-02-22-014) Key scientific research on the inheritance and innovation of Chinese medicine and the development of “Qin Medicine” (2021-03-22-010).