Silibinin Prevents Autophagic Cell Death upon Oxidative Stress in Cortical Neurons and Cerebral Ischemia-Reperfusion Injury
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- 作者：Min Wang ; Yu-Jiao Li ; Yi Ding ; Hui-Nan Zhang ; Ting Sun ; Kun Zhang…
- 关键词：Silibinin ; Oxidative stress ; Antioxidant ; Neuron ; Autophagy ; Apoptosis ; Survival
- 刊名：Molecular Neurobiology
- 出版年：2016
- 出版时间：March 2016
- 年：2016
- 卷：53
- 期：2
- 页码：932-943
- 全文大小：2,246 KB
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Yu-Jiao Li (1)
Yi Ding (2)
Hui-Nan Zhang (1)
Ting Sun (1)
Kun Zhang (1)
Le Yang (1)
Yan-Yan Guo (1)
Shui-Bing Liu (1)
Ming-Gao Zhao (1)
Yu-Mei Wu (1)
1. Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi’an, Shaanxi Province, 710032, People’s Republic of China
2. Department of Pharmacy, Xijing Hospital, the Fourth Military Medical University, Xi’an, Shaanxi Province, 710032, People’s Republic of China - 刊物主题：Neurosciences; Neurobiology; Cell Biology; Neurology;
- 出版者：Springer US
- ISSN：1559-1182
文摘
Neuronal apoptosis and oxidative stress are involved in most of the neurodegenerative diseases, promoting neuron survival is critical for therapy. Silibinin (SLB), which is derived from the seeds of Silybinisus laborinum L., has been widely used as an antioxidant. Here we tested the neuroprotective effects of SLB and the involved molecular mechanisms. We demonstrated that SLB promoted neuron viability upon hydrogen peroxide (H2O2) challenge and reduced hypoxia/ischemia injury in the middle cerebral artery occlusion (MCAO) mouse model. SLB reversed the decreased level of procaspase-3 and balanced Bcl-2 and Bax expression upon H2O2 insult to inhibit cell apoptosis. Furthermore, SLB suppressed the activation of autophagy by decreasing microtubule-associated protein 1 light chain 3 (LC3-II) and Beclin-1 levels under oxidative stress accordingly. SLB phosphorylated protein kinase B (Akt-1) at Ser473 in a time- and dose-dependent manner. The inhibitor for phosphoinositide-3-kinase (PI3K) wortmannin abrogated SLB-induced phosphorylation of Akt-1 and mTOR, decreased the suppression of autophagy, and therefore abolished SLB-mediated neuroprotection. All the data suggested that SLB protected neurons by inhibiting both the mitochondrial and autophagic cell death pathways. This study opens new avenues for the use of SLB in treatment of central nervous system (CNS) diseases in which oxidative stress plays a major role in disease pathogenesis. Given that it occurs naturally with low toxicity and pleiotropic effects that benefit the nervous system, SLB acts potentially as a novel therapy for ischemic injury. Keywords Silibinin Oxidative stress Antioxidant Neuron Autophagy Apoptosis Survival