Aucubin Protects against Myocardial Infarction-Induced Cardiac Remodeling via nNOSNO-Regulated Oxidative Stress

Abstract EN

Whether aucubin could protect myocardial infarction- (MI-) induced cardiac remodeling is not clear.

In this study, in a mouse model, cardiac remodeling was induced by left anterior descending coronary artery ligation surgery.

Mice were intraperitoneally injected with aucubin (10 mg/kg) 3 days post-MI.

Two weeks post-MI, mice in the aucubin treatment group showed decreased mortality, decreased infarct size, and improved cardiac function.

Aucubin also decreased cardiac remodeling post-MI.

Consistently, aucubin protected cardiomyocytes against hypoxic injury in vitro.

Mechanistically, we found that aucubin inhibited the ASK1/JNK signaling.

These effects were abolished by the JNK activator.

Moreover, we found that the oxidative stress was attenuated in both in vivo aucubin-treated mice heart and in vitro-treated cardiomyocytes, which caused decreased thioredoxin (Trx) consumption, leading to ASK1 forming the inactive complex with Trx.

Aucubin increased nNOS-derived NO production in vivo and vitro.

The protective effects of aucubin were reversed by the NOS inhibitors L-NAME and L-VINO in vitro.

Furthermore, nNOS knockout mice also reversed the protective effects of aucubin on cardiac remodeling.

Taken together, aucubin protects against cardiac remodeling post-MI through activation of the nNOS/NO pathway, which subsequently attenuates the ROS production, increases Trx preservation, and leads to inhibition of the ASK1/JNK pathway.