The involvement of endoplasmic reticulum stress in flavonoid-induced protection on cardiac cell death caused by ischaemia/reperfusion

Objectives We have investigated whether endoplasmic reticulum stress and Bcl-2 proteins were linked to the protective effect exerted by flavonoids on ischaemia/reperfusion-induced cardiac damage. Methods Cell viability and immunoblotting were performed. Key findings H9c2 cardiac muscle cells were exposed to flavonoids such as biochanin A, daidzein, genistein, luteolin, quercetin and rutin, followed by ischaemia 12 h/reperfusion 4 h. The flavonoids protected against cell death induced by ischaemia/reperfusion. Flavonoid treatment significantly increased the expression level of the anti-apoptotic protein, Bcl-2, but decreased that of the proapoptotic protein, Bax. The flavonoids down-regulated the expression levels of endoplasmic reticulum stress proteins, glucose-regulated protein-78, activating transcription factor 6α, X-box binding protein 1, inositol-requiring protein-1, phosphor-eukaryotic initiation factor 2α, and C/EBP-homologous protein. Conclusions This study suggested that the protective mechanisms of flavonoids included regulation of Bcl-2/Bax proteins as well as the endoplasmic reticulum stress proteins.