QiShenYiQi pill activates autophagy to attenuate reactive myocardial fibrosis via the PI3K/AKT/mTOR pathway

Aging (Albany NY). 2021 Feb 11;13(4):5525-5538. doi: 10.18632/aging.202482. Epub 2021 Feb 11.

Abstract

QiShenYiQi pill (QSYQ), a traditional Chinese medicine, is used to treat cardiovascular diseases. However, the dose-effect relationship of its intervention in the reactive myocardial fibrosis is elusive. In this work, rat models of reactive myocardial fibrosis induced by partial abdominal aortic coarctation were constructed and randomly classified into the model group, 3-methyladenine group, rapamycin group, QSYQ low-dose group, QSYQ medium-dose group, QSYQ high-dose group, and sham-operated rats (control group). We revealed that QSYQ lowered the heart mass index (HMI), left ventricular mass index (LVMI), and myocardial collagen volume fraction (CVF) levels in a dose-dependent mechanism. Additionally, QSYQ increased the number of autophagosomes, and the expression of myocardial Beclin-1 and LC3B. In contrast, it reduced the expression of myocardial p62 and decreased the ratios of myocardial p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR. In conclusion, our results have revealed that QSYQ impacts anti-reactive myocardial fibrosis in a dose-dependent mechanism which is mediated by the activation of myocardial autophagy via the PI3K/AKT/mTOR pathway.

Keywords: PI3K/AKT/mTOR pathway; autophagy; reactive myocardial fibrosis; traditional Chinese medicine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / drug effects*
  • Beclin-1 / metabolism
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Fibrosis
  • Heart / drug effects*
  • Heart Diseases / drug therapy*
  • Heart Diseases / metabolism
  • Male
  • Microtubule-Associated Proteins / metabolism
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Random Allocation
  • Rats
  • Rats, Wistar
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Beclin-1
  • Becn1 protein, rat
  • Drugs, Chinese Herbal
  • LC3 protein, rat
  • Microtubule-Associated Proteins
  • qishen yiqi
  • mTOR protein, rat
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases