Tilianin is a naturally occurring phenolic compound with a cardioprotective effect against
myocardial ischemia/
reperfusion injury (MIRI). The aim of our study was to determine the potential targets and mechanism of action of
tilianin against cardiac injury induced by MIRI. An in silico docking model was used in this study for binding mode analysis between
tilianin and Ca2+/
calmodulin-dependent protein kinase II (
CaMKII).
Oxygen-
glucose deprivation/reperfusion- (OGD/R-) injured H9c2 cardiomyocytes and
ischemia/reperfusion- (I/R-) injured isolated rat hearts were developed as in vitro and ex vivo models, respectively, which were both treated with
tilianin in the absence or presence of a specific
CaMKII inhibitor
KN93 for target verification and mechanistic exploration. Results demonstrated the ability of
tilianin to facilitater the recovery of OGD/R-induced cardiomyocyte injury and the maintenance of cardiac function in I/R-injured hearts.
Tilianin interacted with CaMKIIδ with an efficient binding performance, a favorable binding score, and restraining p-
CaMKII and ox-
CaMKII expression in cardiomyocytes injured by MIRI. Importantly, inhibition of
CaMKII abolished
tilianin-mediated recovery of OGD/R-induced cardiomyocyte injury and maintenance of cardiac function in I/R-injured hearts, accompanied by the disability to protect mitochondrial function. Furthermore, the protective effects of
tilianin towards mitochondrion-associated proapoptotic and antiapoptotic
protein counterbalance and
c-Jun N-terminal kinase (JNK)/nuclear factor- (NF-) κB-related
inflammation suppression were both abolished after pharmacological inhibition of
CaMKII. Our investigation indicated that the inhibition of
CaMKII-mediated mitochondrial apoptosis and JNK/NF-κB
inflammation might be considered as a pivotal mechanism used by
tilianin to exert its protective effects on MIRI cardiac damage.