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Autophagy as a novel insight into mechanism of Danqi pill against post-acute myocardial infarction heart failure
- Source :
- Journal of Ethnopharmacology. 266:113404
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Ethnopharmacological relevance Danqi Pill, composed of the root of Salvia miltiorrhiza Bunge and the root of Panax notoginseng, is effective in the clinical treatment of myocardial ischemia in coronary heart diseases. A number of studies have shown that autophagy plays an essential role in cardiac function and energy metabolism, and disordered autophagy is associated with the progression of heart failure. However, the effect and mechanism of Danqi pill on autophagy have not been reported yet. Aim of the study This study aims to elucidate whether Danqi pill restores autophagy to protect against HF and its potential mechanism. Materials and methods Left anterior descending ligation was established to induce an HF rat model, H2O2-stimulated H9C2 cells model was conducted to clarify the effects and potential mechanism of Danqi pill. In vivo, Danqi pill (1.5 g/kg) were orally administered for four weeks and Fenofibrate (10 mg/kg) was selected as a positive group. In vitro, Danqi pill (10–200 μg/mL) was pre-cultured for 24 h and co-cultured with H2O2 stimulation for 4 h. Importantly, transmission electron microscopy and fluorescence GPF-mRFP-LC3 reporter system were combined to monitor autophagy flux. Furtherly, we utilized Compound C, a specific AMPK inhibitor, to validate whether the autophagy was mediated by AMPK-TSC2-mTOR pathway. Results Danqi pill significantly improved cardiac function and myocardial injury in HF rats. Intriguingly, Danqi pill potently regulated autophagy mainly by promoting the formation of autophagosomes in vivo. Further results demonstrated that expressions of p-AMPK (P Conclusion Danqi pill could improve cardiac function and protect against cardiomyocytes injury by restoring autophagy via regulating the AMPK-TSC2-mTOR signaling pathway.
- Subjects :
- Male
Cardiac function curve
Myocardial Infarction
AMP-Activated Protein Kinases
Pharmacology
Salvia miltiorrhiza
Cell Line
Rats, Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
Tuberous Sclerosis Complex 2 Protein
Drug Discovery
Autophagy
medicine
Animals
Myocytes, Cardiac
Myocardial infarction
030304 developmental biology
Heart Failure
0303 health sciences
Fenofibrate
Dose-Response Relationship, Drug
business.industry
TOR Serine-Threonine Kinases
AMPK
medicine.disease
Rats
Disease Models, Animal
030220 oncology & carcinogenesis
Heart failure
Ligation
business
Drugs, Chinese Herbal
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 03788741
- Volume :
- 266
- Database :
- OpenAIRE
- Journal :
- Journal of Ethnopharmacology
- Accession number :
- edsair.doi.dedup.....64ee3657646df84156d306ec185869c0