Aims: In the present study, we have investigated the cardioprotective properties of
Isosteviol (STV) under conditions of hypoxia-reoxygenation and elucidated the underlying mechanism.
Background: In our previous studies, we have determined that STV exhibits neuro- and cardio-protective
properties. However, the mechanism underlying STV-induced cardioprotection has not yet
been fully understood.
Methods: All experiments were performed on rat heart embryonic H9c2 cell line. To induce hypoxia-
reoxygenation, cells were exposed to 1% oxygen (in no glucose and no sodium pyruvate
DMEM) following by reoxygenation (using fully supplemented MEM). Cells viability was tested
by MTT assay, and protein levels were compared by Western blotting.
Results: Treatment of heart embryonic H9c2 cells with STV (10 μM) significantly increased the
survival of cells exposed to hypoxia-reoxygenation. STV (10 μM) activated ERK1/2 and DRP1 in
hypoxia-reoxygenation, but did not have any effects on ERK1/2 or DRP1 in normoxia. STV (10
μM) did not regulate CAMKII, AKT or AMPK signaling pathways.
Conclusion: Taken all together, our findings demonstrate that 1) STV protects H9c2 cells against
hypoxia-reoxygenation and that 2) this effect is mediated via ERK1/2. The property of STV that selectively
activates ERK1/2 in cells exposed to stress, but not in cells under non-stress conditions,
makes this compound a promising candidate-drug for therapy against myocardial ischemia-reperfusion
in clinical practice.