Uncovering the molecular mechanisms of Ilex pubescens against myocardial ischemia-reperfusion injury using network pharmacology analysis and experimental pharmacology

2021 ◽  
pp. 114611
Author(s):  
Yuan Zheng ◽  
Sixuan Chen ◽  
Ying Yang ◽  
Xuping Li ◽  
Junxuan Wu ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Network Pharmacology ◽  
Experimental Pharmacology ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Ilex Pubescens

The mechanism of radix paeoniae rubra in treatment of myocardial ischemia-reperfusion injury based on network pharmacology and molecular docking

2021 ◽  
Vol 11 (8) ◽  
pp. 1354-1365
Author(s):  
Meifang Yin ◽  
Lijuan Dai ◽  
Wenpei Ling ◽  
Chunyu Luo ◽  
Shuzhi Qin ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Network Pharmacology ◽  
Signal Pathways ◽  
Active Components ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Radix Paeoniae Rubra (RPR) is a widely used herb medicine. To better understand the mechanism of RPR in the treatment of myocardial ischemia-reperfusion injury (MIRI), in this study, the network of protein–protein interaction of the RPR-MIRI targets was constructed and analyzed through network pharmacology and molecular docking. The enrichment analysis was performed and the network map was established, and the componenttarget network was then verified by molecular docking. In the result, there were 14 components and 52 targets related to MIRI. The results of Gene Ontology (GO) analysis displayed 182 biological processes, 44 cellular components, 56 molecular functions. 45 signal pathways were collected from Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, which were mainly related to Rap1, PI3 K-Akt signal pathway and so on. Molecular docking verified that the active components had lower binding energy with key targets, indicating that it had better binding activity. In conclusion, the treatment of RPR on MIRI is implemented through multi-component, multi-target and multi-pathway, which makes a provision for exploring the therapeutic mechanism of RPR and expanding its clinical application.

Insight into long noncoding RNA–miRNA–mRNA axes in myocardial ischemia-reperfusion injury: the implications for mechanism and therapy

Epigenomics ◽  
2019 ◽  
Vol 11 (15) ◽  
pp. 1733-1748 ◽  
Author(s):  
Wei Xiong ◽  
Yan Qu ◽  
Hongmei Chen ◽  
Jinqiao Qian
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Noncoding Rnas ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Insight Into

Emerging evidence has demonstrated that regulatory noncoding RNAs (ncRNAs), such as long noncoding RNAs (lncRNAs) and miRNAs, play crucial roles in the initiation and progress of myocardial ischemia-reperfusion injury (MIRI), which is associated with autophagy, apoptosis and necrosis of cardiomyocytes, as well as oxidative stress, inflammation and mitochondrial dysfunction. LncRNAs serve as a precursor or host of miRNAs and directly/indirectly affecting miRNAs via competitive binding or sponge effects. Simultaneously, miRNAs post-transcriptionally regulate the expression of genes by targeting various mRNA sequences due to their imperfect pairing with mRNAs. This review summarizes the potential regulatory role of lncRNA–miRNA–mRNA axes in MIRI and related molecular mechanisms of cardiac disorders, also provides insight into the potential therapies for MIRI-induced diseases.

scholarly journals The Emerging Role of Thioredoxin-Interacting Protein in Myocardial Ischemia/Reperfusion Injury

2016 ◽  
Vol 22 (3) ◽  
pp. 219-229 ◽  
Author(s):  
Bing F. Wang ◽  
Jun Yoshioka
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Interacting Protein ◽  
Glucose Transporter 1 ◽  
Thioredoxin Interacting Protein ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Myocardial ischemia/reperfusion injury represents a major threat to human health and contributes to adverse cardiovascular outcomes worldwide. Despite the identification of numerous molecular mechanisms, understanding of the complex pathophysiology of this clinical syndrome remains incomplete. Thioredoxin-interacting protein (Txnip) has been of great interest in the past decade since it has been reported to be a critical regulator in human diseases with several important cellular functions. Thioredoxin-interacting protein binds to and inhibits thioredoxin, a redox protein that neutralizes reactive oxygen species (ROS), and through its interaction with thioredoxin, Txnip sensitizes cardiomyocytes to ROS-induced apoptosis. Interestingly, evidence from recent studies also suggests that some of the effects of Txnip may be unrelated to changes in thioredoxin activity. These pleiotropic effects of Txnip are mediated by interactions with other signaling molecules, such as nod-like receptor pyrin domain-containing 3 inflammasome and glucose transporter 1. Indeed, Txnip has been implicated in the regulation of inflammatory response and glucose homeostasis during myocardial ischemia/reperfusion injury. This review attempts to make the case that in addition to interacting with thioredoxin, Txnip contributes to some of the pathological consequences of myocardial ischemia and infarction through endogenous signals in multiple molecular mechanisms.

Mechanisms of Paeoniflorin against myocardial ischemia reperfusion injury based on network pharmacology

2021 ◽  
Vol 11 (9) ◽  
pp. 1505-1515
Author(s):  
Chengguo Zhao ◽  
Meifang Yin ◽  
Feng Li ◽  
Wenpei Ling ◽  
Chunyu Luo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Network Pharmacology ◽  
Tunel Staining ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Myocardial Enzymes

Ischemic heart disease (IHD) is the primary reason of death of cardiovascular diseases. Paeoniflorin (PF), a monoterpene glycoside extracted from Radix Paeoniae Rubra or Paeoniae Radix Alba, can ameliorate myocardial ischemia/reperfusion injury (MIRI), but its mechanism is not still defined. In this study, network pharmacology was utilized, the protein interaction network between PF and MIRI targets were screened for bioenrichment analysis. Moreover, the anti-MIRI effects of PF (30, 60 and 120 mg/kg) were investigated in vivo on rats for verification. The myocardial infarction area was assessed by TTC/Evans blue staining and morphological changes of tissues were evaluated using hematoxylin and eosin staining. The contents of myocardial enzymes and oxidation resistance were measured. The cell apoptosis was evaluated using TUNEL staining and the expression of proteins was estimated using Western Blot. In the results, the relevant targets and the biological processes of PF against MIRI were screened out, indicating its anti-MIRI potential pharmacological effects of PF. 120 mg/kg PF can shrink infarction area after ischemia/reperfusion, ameliorate pathological morphology in myocardial tissue, lower the levels of myocardial enzymes, and attenuate oxidative stress. Furthermore, PF could reduce the positive rate of TUNEL staining caused by MIRI. Moreover, 120 mg/kg PF could depress the protein levels of Bax, Caspase-3, Beclin-1 and Cathepsin B and increase the protein level of Bcl-2 on rats after reperfusion. In conclusion, Paeoniflorin has an anti-MIRI effect in rats via coordinate regulation of anti-oxidative stress, anti-apoptosis and inhibition of autophagy.

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