Myocardial ischemia reperfusion injury (MIRI) is a complex pathophysiological process involved with the activation of oxidative stress, inflammation and apoptosis. Sappanone A (SA), a homoisoflavanone isolated from the heartwood of Caesalpinia sappan L., could exhibit antioxidant, anti-inflammatory and anti-apoptotic activities. Therefore, we assumed that SA has a potential use for preventing against MIRI. This study aimed to investigate the effect of SA treatment on MIRI and its mechanism. Cardiomyocytes (H9c2 cells) were treated with SA for 1 h, followed by 6 h of hypoxia/3 h of reoxygenation. Cell viability assay was detected by CCK-8 assay. Apoptosis was measured by flow cytometry and Hoechst staining. Mitochondrial permeability transition pore (mPTP) opening and mitochondrial transmembrane potential (ΔΨm) were measured by spectrophotometry and JC-1 staining. The changes of mitochondrial apoptosis-related proteins and PI3K-Akt-Gsk-3β signaling pathway were evaluated by Western blotting. The results showed that SA pretreatment enhanced the cell viability and decreased the activity of myocardial enzyme in a dose-dependent manner. Moreover, SA pretreatment significantly inhibited apoptosis, blocked mPTP opening, suppressed the release of ΔΨm, prevented the cytochrome c releasing from mitochondria into cytoplasm, and repressed the cleavage of caspase-9 and caspase-3. Furthermore, SA pretreatment increased the phosphorylation levels of Akt and Gsk-3β but not of Stat-3. Meanwhile, the protective effect of SA was abrogated by PI3K inhibitor (LY294002). In conclusion, our results demonstrate that SA could prevent hypoxia/reoxygenation-induced cardiomyocytes injury through inhibition of mitochondrial apoptosis and activation of PI3K-Akt-Gsk-3β pathway. Thus, SA may have a potential use for the prevention of MIRI.

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