Tetrandrine (TET), a
bisbenzylisoquinoline alkaloid has been used for the treatment of
cardiovascular diseases and
hypertension. This study was to investigate whether
tetrandrine exerts cardioprotection in
ischemia-reperfusion (I/R) injury and the mechanisms involved. The cardioprotection effect and mechanisms of
tetrandrine was evaluated by I/R injury cardiac cell model.
Hexokinase II (HKII) is the critical regulators of
mitochondrial dysfunction in cardiac I/R injury and it participate in the regulation of glycolysis and energy metabolism. The effect of
tetrandrine on HKII and
Janus kinase (JAK), (
Protein kinase B)Akt as well as
hypoxia inducible factor α (HIF-α) which are HKII's regulator was also investigated. We found that
tetrandrine significantly reduced
lactate dehydrogenase,
caspase 3 level and apoptosis in I/R injury cardiac cell, meanwhile restored mitochondrial energy metabolism and enhanced glycolysis in model cell.
Tetrandrine up-regulated the expression of p-STAT3 and HKII, but has no effect on p-akt and HIF-α. The cardioprotection effect significantly attenuated after
tetrandrine combined with JAK3 inhibitor. The expression of p-STAT3 and HK II were also significantly decreased simultaneously. On the contrary, combined with JAK1/2 inhibitor, there was no significant influence. In addition,
tetrandrine increased the JAK3 in model cells, but have no impact on the expression of JAK1, JAK2. Taken together, these data revealed that the cardioprotection effect of
tetrandrine appears to be involved in the JAK3/STAT3 /HK II.