A novel danshensu/tetramethypyrazine derivative attenuates oxidative stress-induced autophagy injury via the AMPK-mTOR-Ulk1 signaling pathway in cardiomyocytes.

Myocardial ischemia/reperfusion injury (MIRI) is an inevitable and unsolved clinical problem in the treatment of ischemic heart diseases. Compound DT-010 is a novel danshensu/tetramethylpyrazine derivative and was examined as a candidate for treating MIRI. In the present study, MTT, lactate dehydrogenase assay and Hoechst staining data indicated that DT-010 attenuated tert-butylhydroperoxide (t-BHP)-induced oxidative damage by increasing cell survival, reducing cell damage and decreasing apoptosis in H9c2 cardiomyocytes.

A novel Danshensu/tetramethylpyrazine derivative induces vasorelaxation on rat aorta and exerts cardioprotection in dogs.

ADTM, a previously reported novel Danshensu (DSS)/tetramethylpyrazine (TMP) derivative with cardioprotective and antiplatelet aggregative effects, is a promising therapeutic candidate for ischemic heart diseases. In the present study, ADTM increased coronary blood flow and protected myocardium against ischemic injury in dogs. In addition, the relaxing effect of ADTM on rat thoracic aorta and its underlying mechanisms were examined.

A Novel Danshensu-Tetramethylpyrazine Conjugate DT-018 Provides Cardioprotection by Preserving Mitochondrial Function Through the MEF2D/PGC-1α Pathway.

In this work, we explored the protective effect of DT-018, a danshensu and tetramethylpyrazine conjugate, on mitochondrial injury induced by tert-butylhydroperoxide (t-BHP) and its possible mechanisms of action. DT-018 effectively quenched intracellular and mitochondrial reactive oxygen species (ROS), preserved the mitochondrial function, restored the intracellular level of ATP and augmented mitochondrial membrane potential (Δψm) while suppressed mitochondrial swelling in isolated myocardial mitochondria. DT-018 increased the expression of MEF2D and PGC-1α as well as Nrf2 and Tfam in H9c2 cells.

A Novel Danshensu-Tetramethylpyrazine Conjugate DT-010 Provides Cardioprotection through the PGC-1α/Nrf2/HO-1 Pathway.

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 (·O), hydroxyl radical (·OH) and peroxynitrite anion (ONOO) after t-BHP exposure.