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

Abstract

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.

The Shexiang Baoxin Pill Protects Myocardial Cells from Multiple Targets of MIRI through the PI3K/Akt/eNOS Signal Pathway

“…MIRI is a common pathophysiological injury in STEMI patients [30], which can increase the area of myocardial infarction and adversely affect patient prognosis [4]. A compound preparation of traditional Chinese medicine, SBP can reduce MIRI and myocardial infarction area[21].…”

Protective effect of colchicine on albumin glycation and cellular oxidative stress: Insights into diabetic cardiomyopathy

“…Media was changed every 2-3 days. Cardiomyoblasts (70%-80% confluent) were pretreated with given treatments, [33][34][35] native HSA (400 μg/mL), glycated HSA (HSA + MGO, 400 μg/mL), glycated HSA (400 μg/mL) + FPS-ZM1 (100 nM), glycated HSA (400 μg/mL) + COL 2.5 μM (400 μg/mL), glycated HSA (400 μg/mL) + COL 3.75 μM (400 μg/mL), and glycated HSA (400 μg/mL) + COL 5 μM (400 μg/mL). After 24-h incubation, cells were given a PBS wash once, and treated cell supernatants were…”

Research Progress on the Role of Pyroptosis in Myocardial Ischemia-Reperfusion Injury

“…The pretreatment with colchicine reduces myocardial infarct size and induces cardioprotection associated with anti-inflammatory effects during the early reperfusion phase. In fact, colchicine can lead to MIRI inhibition through multiple mechanisms and MIRI-induced myocardial injury inhibition by a reduction in caspase-3 levels and activation of the PI3K/AKT/eNOS pathway in H9C2 cells undergoing apoptosis in a hypoxia/deoxygenation-induced myocardial injury model [ 88 ]. Moreover, it also plays important role in sympathetic denervation [ 89 ] and reduction in cardiac fibrosis [ 90 ].…”