Plant Natural Product Formononetin Protects Rat Cardiomyocyte H9c2 Cells against Oxygen Glucose Deprivation and Reoxygenation via Inhibiting ROS Formation and Promoting GSK-3β Phosphorylation

Figure 6

Proposed mechanism underlying the cardioprotective effect of formononetin. Formononetin activates PI3K/Akt and PKC signaling pathways and subsequently induces the phosphorylation of GSK-3β at Ser9. The phosphorylation of GSK-3β at Ser9 leads to the inactivation of GSK-3β in the opening of mPTP. On the other hand, phospho-GSK-3β (Ser9) migrates towards mitochondria and binds to ANT, causing the disassociation of the mPTP complex involving ANT, Cyp-D, VDAC, and HKII. Formononetin also inhibits the overproduction of ROS and superoxide, possibly reducing the oxidative damage of mitochondria in cardiomyocytes.