Protective effects of hederagenic acid on PC12 cells against the OGD/R-induced apoptosis via activating Nrf2/ARE signaling pathway

Abstract

Cerebral ischemic stroke is a severe cause of disability and death among people worldwide. The occlusion of cerebral blood flow has resulted in the infarction due to the oxygen and glucose deprivation. Though timely reperfusion can reduce the infarct size, the oxidative stress triggered in ischemia and reperfusion will induce apoptosis of neurons in penumbra. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor regulating the expression of antioxidant enzymes through binding to antioxidant response elements (ARE). The activation of Nrf2/ARE pathway can protect neurons against oxidative stress. To discover novel drugs targeting cerebral ischemic stroke, we have assessed the protective effects of hederagenic acid on PC12 cells injured by oxygen and glucose deprivation/restoration (OGD/R) and explored the possible mechanisms. The results showed hederagenic acid could enhance the survival of PC12 cells exposed to OGD/R. Further exploration has revealed oxidative stress and mitochondrial dysfunction in PC12 cells have been attenuated by hederagenic acid. Meanwhile, the apoptosis in PC12 cells has been inhibited significantly. In addition, activation of Nrf2/ARE pathway by hederagenic acid was observed herein, which indicated this cascade was involved in the protective effects. These results can provide proofs for the further investigation in vivo and the discovery of new drugs targeting cerebral ischemic stroke.