Protective effects of hederagenic acid on PC12 cells against the OGD/R-induced apoptosis via activating Nrf2/ARE signaling pathway
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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.
KeywordsHederagenic acid Ischemic stroke PC12 cells Apoptosis Nrf2/ARE pathway
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Conflict of interest
The authors declare that they have no conflict of interest.
- Chao XD, Ma YH, Luo P, Cao L, Lau WB, Zhao BC, Han F, Liu W, Ning WD, Su N, Zhang L, Zhu J, Fei Z, Qu Y (2013) Up-regulation of heme oxygenase-1 attenuates brain damage after cerebral ischemia via simultaneous inhibition of superoxide production and preservation of NO bioavailability. Exp Neurol 239:163–169PubMedCrossRefGoogle Scholar
- Chen H, Yoshioka H, Kim GS, Jung JE, Okami N, Sakata H, Maier CM, Narasimhan P, Goeders CE, Chan PH (2011) Oxidative stress in ischemic brain damage: mechanisms of cell death and potential molecular targets for neuroprotection. Antioxid Redox Signal 14:1505–1517PubMedPubMedCentralCrossRefGoogle Scholar
- Lee CW, Park SM, Zhao R, Lee C, Chun W, Son Y, Kim SH, Jung JY, Jegal KH, Cho IJ, Ku SK, Kim YW, Ju SA, Kim SC, An WG (2015) Hederagenin, a major component of Clematis mandshurica Ruprecht root, attenuates inflammatory responses in RAW 264.7 cells and in mice. Int Immunopharmacol 29:528–537PubMedCrossRefGoogle Scholar