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

Author(s):  
Ying Yang ◽  
Ting Chen ◽  
Jiaming Liu ◽  
Sixuan Chen ◽  
Rongqing Cai ◽  
...  

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.

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuanjun Tang ◽  
Chenyang Shi ◽  
Yingyi Qin ◽  
Shuowen Wang ◽  
Hui Pan ◽  
...  

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.


2021 ◽  
Vol 11 (8) ◽  
pp. 1354-1365
Author(s):  
Meifang Yin ◽  
Lijuan Dai ◽  
Wenpei Ling ◽  
Chunyu Luo ◽  
Shuzhi Qin ◽  
...  

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.


Sign in / Sign up

Export Citation Format

Share Document