Mechanistic analysis of Tanshinone IIA's regulation of the ATM/GADD45/ORC signaling pathway to reduce myocardial ischemia-reperfusion injury.

BACKGROUND: By far, one of the best treatments for myocardial ischemia is reperfusion therapy. The primary liposoluble component of Danshen, a traditional Chinese herbal remedy, Tanshinone ⠡A, has been shown to have cardiac healing properties. The purpose of this work is to investigate the processes by which Tanshinone ⠡A influences myocardial ischemia-reperfusion injury (MIRI) in the H9C2 cardiac myoblast cell line, as well as the association between Tanshinone ⠡A and MIRI. METHODS AND RESULTS: The cardiac cells were divided into a normal group, a model group and Tanshinone ⠡A treatment groups. After 4 h of culture with the deprivation of oxygen and glucose, the cells were incubated normally for 2 h. The success of the model and the capacity of Tanshinone ⠡A to heal cardiac damage were validated by the outcomes of cell viability, morphology, and proliferation. The efficacy of Tanshinone ⠡A in treating MIRI was further confirmed by the scratch assay and biomarker measurement. The differentially expressed genes were examined using transcriptome sequencing. The Ataxia-Telangiectasia Mutated (ATM)/Growth Arrest and DNA Damage (GADD45)/Origin Recognition Complex (ORC) signaling pathway was identified as being crucial to this process by KEGG pathway analysis and GO enrichment. Molecular docking and RT-qPCR were used to confirm our results. The crucial function of the ATM/GADD45/ORC pathway was further confirmed by the addition of an ATM inhibitor, which inhibited the expression of ATM. CONCLUSION: Tanshinone ⠡A can relieve the myocardial ischemia-reperfusion injury in cardiac cells by activating the ATM/GADD45/ORC pathway.