Yangxinkang tablet protects against cardiac dysfunction and remodelling after myocardial infarction in rats through inhibition of AMPK/mTOR-mediated autophagy

Autor: Han-Ping Zhu, Zhen-Qiu Li, Pei-Hua Ren, Peng Wang, Zhi-Min Zhang
Rok vydání: 2020
Předmět:
medicine.medical_specialty
Heart Injury
Chinese patent medicine
Cardiac fibrosis
cardiac fibrosis
Myocardial Infarction
acute myocardial infarction
Pharmaceutical Science
Apoptosis
Context (language use)
RM1-950
AMP-Activated Protein Kinases
Protective Agents
030226 pharmacology & pharmacy
01 natural sciences
Ventricular Function
Left
Cardiac dysfunction
Ventricular Dysfunction
Left
03 medical and health sciences
0302 clinical medicine
Ampk mtor
Internal medicine
Drug Discovery
Autophagy
Animals
heart injury
Medicine
cardiovascular diseases
Myocardial infarction
Rats
Wistar
Pharmacology
Ventricular Remodeling
business.industry
TOR Serine-Threonine Kinases
General Medicine
medicine.disease
Rats
0104 chemical sciences
010404 medicinal & biomolecular chemistry
chinese herbal compound
Complementary and alternative medicine
Cardiology
Molecular Medicine
Therapeutics. Pharmacology
business
Research Article
Drugs
Chinese Herbal
Signal Transduction
Zdroj: Pharmaceutical Biology, Vol 58, Iss 1, Pp 321-327 (2020)
Pharmaceutical Biology
ISSN: 1744-5116
1388-0209
DOI: 10.1080/13880209.2020.1748662
Popis: Context: Acute myocardial infarction (AMI) is defined as myocardial necrosis. Clinicians use the traditional Chinese patent medicine Yangxinkang Tablet (YXK) to treat chronic heart failure. Objective: To explore the effects of YXK on heart injury following AMI and the underlying mechanisms. Materials and methods: The AMI model was produced in Wistar rats by permanent ligation of the left anterior descending coronary artery. Rats were divided into the following five groups: Sham (n = 6), MI (Model, n = 10), AICAR (AMPK agonist, 50 mg/kg/d, i.p., n = 10), Compound C (AMPK inhibitor, 10 mg/kg/d, i.p., n = 10), and YXK (0.72 g/kg/d, gavage, n = 10) groups. Cardiac function, cardiac fibrosis, apoptosis, and expression of p-AMPK, p-mTOR, and autophagy-related proteins was measured after 4 weeks of treatment after the successful modelling of the AMI. Results: Compared to MI group, both YXK and AMPK inhibitor improved cardiac dysfunction and reduced cardiac fibrosis (15.6 ± 2.3; 22.6 ± 4.6 vs. 34.6 ± 4.3%) and myocardial cell apoptosis (12 ± 3.67; 25.6 ± 6.8 vs. 54 ± 4.8%). Futhermore, YXK and AMPK inhibitor significantly decreased p-AMPK expression by 11.05% and 14.64%, LC3II/I by 25.08% and 35.28% and Beclin-1 by 66.71% and 33.85%, increased p-mTOR by 22.14% and 47.46% and p62 by 70.83% and 18.58%. Conclusions: The underlying mechanism appears to include suppression of autophagy via inhibiting AMPK/mTOR signalling, suggesting that YXK may serve as a potentially effective Chinese herbal compound for suppressing cardiac fibrosis in heart injury.
Databáze: OpenAIRE
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