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.

scholarly journals microRNA-130a-5p suppresses myocardial ischemia reperfusion injury by downregulating the HMGB2/NF-κB axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yong Li ◽  
Hongbo Zhang ◽  
Zhanhu Li ◽  
Xiaoju Yan ◽  
Yuan Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Mouse Models ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Luciferase Reporter ◽  
Gene Assay ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Abstract Background Myocardial ischemia reperfusion injury (MIRI) is defined as tissue injury in the pathological process of progressive aggravation in ischemic myocardium after the occurrence of acute coronary artery occlusion. Research has documented the involvement of microRNAs (miRs) in MIRI. However, there is obscure information about the role of miR-130a-5p in MIRI. Herein, this study aims to investigate the effect of miR-130a-5p on MIRI. Methods MIRI mouse models were established. Then, the cardiac function and hemodynamics were detected using ultrasonography and multiconductive physiological recorder. Functional assays in miR-130a-5p were adopted to test the degrees of oxidative stress, mitochondrial functions, inflammation and apoptosis. Hematoxylin and eosin (HE) staining was performed to validate the myocardial injury in mice. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was employed to assess the expression patterns of miR-130a-5p, high mobility group box (HMGB)2 and NF-κB. Then, dual-luciferase reporter gene assay was performed to elucidate the targeting relation between miR-130a-5p and HMGB2. Results Disrupted structural arrangement in MIRI mouse models was evident from HE staining. RT-qPCR revealed that overexpressed miR-130a-5p alleviated MIRI, MIRI-induced oxidative stress and mitochondrial disorder in the mice. Next, the targeting relation between miR-130a-5p and HMGB2 was ascertained. Overexpressed HMGB2 annulled the protective effects of miR-130a-5p in MIRI mice. Additionally, miR-130a-5p targets HMGB2 to downregulate the nuclear factor kappa-B (NF-κB) axis, mitigating the inflammatory injury induced by MIRI. Conclusion Our study demonstrated that miR-130a-5p suppresses MIRI by down-regulating the HMGB2/NF-κB axis. This investigation may provide novel insights for development of MIRI treatments.

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.

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