scholarly journals Network Pharmacology-Based Investigation and Experimental Exploration of the Antiapoptotic Mechanism of Colchicine on Myocardial Ischemia Reperfusion Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuanjun Tang ◽  
Chenyang Shi ◽  
Yingyi Qin ◽  
Shuowen Wang ◽  
Hui Pan ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Kegg Pathway ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Network Pharmacology ◽  
H9c2 Cell ◽  
Pathway Enrichment ◽  
Pharmacological Mechanism ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Background: The beneficial effects of colchicine on cardiovascular disease have been widely reported in recent studies. Previous research demonstrated that colchicine has a certain protective effect on ischemic myocardium and has the potential to treat myocardial ischemia reperfusion injury (MIRI). However, the potential targets and pharmacological mechanism of colchicine to treat MIRI has not been reported.Methods: In this study, we used network pharmacology and experimental verification to investigate the pharmacological mechanisms of colchicine for the treatment of MIRI. Potential targets of colchicine and MIRI related genes were screened from public databases. The mechanism of colchicine in the treatment of MIRI was determined by protein-protein interaction (PPI), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Additionally, we evaluated the effect of colchicine on H9C2 cell activity using CCK-8 assays, observed the effect of colchicine on H9C2 cell apoptosis via flow cytometry, and further verified the expression of key targets after colchicine treated by Western blot.Results: A total of 626 target genes for colchicine and 1549 MIRI disease targets were obtained. 138 overlapping genes were determined as potential targets of colchicine in treating MIRI. the PPI network analysis demonstrated that the targets linked to MIRI were ALB, TNF, ACTB, AKT1, IL6, TP53, IL1B, CASP3 and these targets showed nice affinity with colchicine in molecular docking experiments. The results of GO analysis and KEGG pathway enrichment demonstrated that the anti-MIRI effect of colchicine involves in apoptotic signaling pathway. Further tests suggested that colchicine can protect H9C2 cell from Hypoxia/Reoxygenation (H/R) injury through anti-apoptotic effects. Western blot results demonstrated that colchicine can inhibited MIRI induced apoptosis of H9C2 cell by enhancing the decreased levels of Caspase-3 in myocardial injure model induced by H/R and activating the PI3K/AKT/eNOS pathway.Conclusions: we performed network pharmacology and experimental evaluation to reveal the pharmacological mechanism of colchicine against MIRI. The results from this study could provide a theoretical basis for the development and clinical application of colchicine.

scholarly journals Identifying the Chemical Profile and Pharmacological Mechanism of Xinbao Pill against Myocardial Ischemia-Reperfusion Injury Using Ultra-Fast Liquid Chromatography-Quadrupole-Time-Of-Flight Tandem Mass Spectrometry Coupled with Network Pharmacology-Based Investigation

2021 ◽  
Author(s):  
Ying Yang ◽  
Ting Chen ◽  
Jiaming Liu ◽  
Sixuan Chen ◽  
Rongqing Cai ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Signaling Pathway ◽  
Kegg Pathway ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cardioprotective Effect ◽  
Network Pharmacology ◽  
Pathway Enrichment ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Abstract Background: Xinbao Pill (Xin-Bao-Wan, XBW) is a traditional Chinese herbal formula, which is widely used in clinical treatment for cardiovascular diseases; however, the therapeutic effect of XBW on myocardial ischemia-reperfusion injury (MI/RI) is unclear. In this study, we evaluated the cardioprotective effect and molecular mechanism of XBW against MI/RI.Methods: A phytochemistry-based network pharmacology analysis was used to uncover the mechanism of XBW against MI/RI. Firstly, ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) method was used to identify chemicals in XBW. MI/RI-related targets of XBW were predicted using TargetNet database, OMIC database and reported literatures. GO and KEGG pathway enrichment analyses were performed using String database. Left anterior descending artery (LAD) ligation-induced MI/RI rat model and oxygen glucose deprivation-reperfusion (OGD/R)-induced H9c2 cell model were used to evaluate the cardioprotective effect and potential mechanism of XBW.Results: 37 chemicals were identified in XBW by using UHPLC-QTOF-MS; 50 MI/RI-related targets of XBW were predicted using TargetNet database, OMIC database and reported literatures. In vivo study, XBW (180 mg/kg) significantly reduced myocardial infarct size and creatine kinase MB (CK-MB) level induced by MI/RI in rat model; in vitro study, XBW protected H9c2 cells against OGD/R injury in a dose-dependent manner. GO and KEGG pathway enrichment analyses showed that the cardioprotective effect of XBW was associated with 5 significant pathways including autophagy, apoptosis, HIF-1 signaling pathway, PI3K-Akt signaling pathway, FoxO signaling pathway. Experimental investigation also verified that XBW could suppress apoptosis, autophagy and endoplasmic reticulum (ER) stress.Conclusion: XBW showed therapeutic effects against MI/RI mainly via attenuating apoptosis though suppressing excessive autophagy and ER stress.

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.

scholarly journals PLCE1 promotes myocardial ischemia–reperfusion injury in H/R H9c2 cells and I/R rats by promoting inflammation

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
WenHua Li ◽  
Yong Li ◽  
Ying Chu ◽  
WeiMin Wu ◽  
QiuHua Yu ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Underlying Mechanism ◽  
H9c2 Cell ◽  
Injury Model ◽  
Tnf Α ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Artery Disease ◽  
Myocardial Ischemia Reperfusion

Abstract Myocardial ischemia–reperfusion (I/R) injury is a major contributor to the morbidity and mortality associated with coronary artery disease. How to ensure the recovery of blood supply to ischemic myocardial tissue while avoiding or reducing I/R injury remains a critical problem in clinical practice. In the present study, we examined the function of phospholipase C ϵ-1 (PLCE1) by an H9c2 H/R (H/R, hypoxia–reoxygenation) model and a rat myocardial I/R injury model. The expression of PLCE1 and its effect on I/R injury-induced inflammatory response as well as its possible underlying mechanism were investigated. Our results have shown that PLCE1 was progressively increased along with the increase in hypoxia time in the H/R H9c2 and HL-1 cells. In myocardial I/R rats, PLCE1 presented a low expression level in the sham group, however, it was increased sharply in the I/R group. Overexpression of PLCE1 promoted the expression of IL-6, TNF-α, and IL-1α, and decreased the expression of IL-10. Knockdown of PLCE1 decreased the expression of IL-6, TNF-α, and IL-1α, and increased the expression of IL-10. Furthermore, overexpression of PLCE1 increased the phosphorylation of p38, ERK1/2, and nuclear factor-κ B (NF-κB) P65 while knockdown of PLCE1 inhibited their phosphorylation. In conclusion, the present study provided evidence that PLCE1 was up-regulated in H/R H9c2 cell and I/R rat. Overexpression of PLCE1 promoted the inflammatoion via activation of the NF-κB signaling pathway.

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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