1. Autophagy as a novel insight into mechanism of Danqi pill against post-acute myocardial infarction heart failure
- Author
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Lei Peng, Qiyan Wang, Xiaoping Wang, Chun Li, Dongqing Guo, Jiang Yanyan, Xue Tian, Qianbin Sun, Qian Zhang, Yong Wang, and Xin-lou Chai
- 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 - 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.
- Published
- 2021