A novel Danshensu-tetramethylpyrazine conjugate DT-010 provides cardioprotection through the PGC-1α/Nrf2/HO-1 pathway

抄録

In this study, we investigated the cardioprotective mechanisms of action of DT-010, a novel danshensu-tetramethylpyrazine conjugate. DT-010 significantly preserved cell viability and suppressed cell apoptosis in H9c2 cells injured by tert-butylhydroperoxide (t-BHP), iodoacetic acid (IAA) and hypoxia-reoxygenation. In addition, DT-010 pre-treatment reduced the intracellular level of free radicals including superoxide anion (•O₂^－), hydroxyl radical (•OH) and peroxynitrite anion (ONOO^－) after t-BHP exposure. Moreover, DT-010 up-regulated the protein expression of PGC-1α and Nrf2 as well as Tfam and HO-1 in H9c2 cells. DT-010 also triggered Nrf2 nuclear translocation. In a rat myocardial ischemia-reperfusion model, DT-010 significantly alleviated myocardial infarction. The results indicated that DT-010 may be a promising candidate for the treatment of cardiovascular diseases, particularly myocardial ischemia and reperfusion injury.