Icariin Inhibits AGE-Induced Injury in PC12 Cells by Directly Targeting Apoptosis Regulator Bax

الملخص EN

Diabetic encephalopathy (DE) is a serious complication caused by long-term cognitive impairment in diabetic patients.

At present, there is no effective treatment for DE.

Icariin (ICA) is a bioactive ingredient isolated from Epimedium.

Previous research indicated that ICA was neuroprotective against Aβ-induced PC12 cell insult; however, the effect of ICA on an advanced glycosylation end product- (AGE-) induced neural injury model has not been studied.

In this study, we investigated the neuroprotective effects of ICA on AGE-induced injury in PC12 cells.

Our findings revealed that ICA could effectively protect PC12 cells from AGE-induced cell apoptosis by suppressing oxidative stress.

Moreover, we observed that ICA could significantly protect against mitochondrial depolarization following AGE stimulation and inactivate the mitochondria-dependent caspase-9/3 apoptosis pathway.

Most notably, we identified the direct target protein of ICA as apoptosis regulator Bax by a pulldown assay.

We found that ICA could specifically target Bax protein and inhibit Bax dimer formation and migration to mitochondria.

Furthermore, a siRNA knockdown experiment revealed that ICA could inhibit PC12 cell apoptosis and oxidative stress through targeting Bax.

Taken together, our findings demonstrated that ICA could attenuate AGE-induced oxidative stress and mitochondrial apoptosis by specifically targeting Bax and further regulating the biological function of Bax on mitochondria.