Integrating network analysis and experimental validation to reveal the mitophagy-associated mechanism of Yiqi Huoxue (YQHX) prescription in the treatment of myocardial ischemia/reperfusion injury

https://doi.org/10.1016/j.phrs.2023.106682Get rights and content
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Abstract

Myocardial ischemia/reperfusion (I/R) injury is the main cause of increasing postischemic heart failure and currently there is no definite treatment for myocardial I/R injury. It has been suggested that oxidative stress-induced mitochondrial dysfunction plays an important role in the pathological development of myocardial I/R. In this study, Yiqi Huoxue (YQHX) prescription, as a kind of Chinese herbal formula, was developed and shown to alleviate I/R injury. Network analysis combined with ultrahigh-performance liquid chromatography-high resolution mass spectrometry expounded the active components of YQHX and revealed the mitophagy-regulation mechanism of YQHX treating I/R injury. In vivo experiments confirmed YQHX significantly alleviated I/R myocardial injury and relieved oxidative stress. In vitro experiments validated that YQHX could relieve hypoxia/reoxygenation injury and attenuate oxidative stress via improving the structure and function of mitochondria, which was strongly related to regulating mitophagy. In summary, this study demonstrated that YQHX, which could alleviate I/R injury via targeting mitophagy, might be a potential therapeutic strategy for myocardial I/R injury.

Abbreviations

ADO
adenosine
AMPK
Adenosine 5′ monophosphate activated protein kinase
AMI
acute myocardial infarction
AP
autophagosomes
AKT
Protein kinaseB
ASS
autophagolysosomes
ATP
adenosine triphosphate
Bcl-2
B-cell lymphoma-2
BX
Pinelliae Rhizoma Praeparatum
BYHW
Buyang Huanwu
BZ
Atractylodis Macrocephalae Rhizoma
CEs
collision energies
CHD
coronary heart disease
CK
creatine kinase
CTD
comparative toxicogenomics database
CX
Chuanxiong Rhizoma
DCFH-DA
2′,7′-dichlorodihydrofluorescein diacetate
DDA
data-dependent acquisitio
DG
Angelicae Sinensis Radix
DL
Pheretima
DS
Codonopsis Radix
ESI
electrospray ionization
FL
Poria
GO
Gene Ontology
H&E
hematoxylin-eosin staining
H/R
Hypoxia/reoxygenation
HCD
high-energy dissociation
HQ
Astragali Radix
I/R
ischemia/reperfusion
JH
Citri Exocarpium Rubrum
KEGG
Kyoto Encyclopedia of Genes and Genomes
LAD
left anterior descending coronary artery
LDH
lactate dehydrogenase
MCODE
Molecular Complex Detection
MDA
malondialdehyde
MMP
mitochondrial membrane potential
PB
phosphate buffer
PPI
Protein-protein interaction
PI3K
Phosphatidylinositol 3 kinase
ROS
reactive oxygen species
SOD
superoxide dismutase
SQ
Notoginseng Radix et Rhizoma
SZ
Hirudo
TCM
traditional Chinese medicine
TCMIP
Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine
TCMSP
Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform
TEM
transmission electron microscopy
TTC
triphenyl tetrazolium chloride
TTD
theoretical target database
UPLC-HRMS
ultrahigh-performance liquid chromatography-high resolution mass spectrometry
YQHX
Yiqi Huoxue
YYR
Coicis Semen

Key words

Myocardial ischemia/reperfusion injury
Yiqi Huoxue
Mitophagy
Network pharmacology
Traditional Chinese medicine

Data availability

The data that has been used is confidential.

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Equal contribution to this paper