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| Content Provider | Springer Nature Link |
|---|---|
| Author | Wang, Min Li, Yu Jiao Ding, Yi Zhang, Hui Nan Sun, Ting Zhang, Kun Yang, Le Guo, Yan Yan Liu, Shui Bing Zhao, Ming Gao Wu, Yu Mei |
| Copyright Year | 2014 |
| Abstract | 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 (H$_{2}$O$_{2}$) 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 H$_{2}$O$_{2}$ 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. |
| Starting Page | 932 |
| Ending Page | 943 |
| Page Count | 12 |
| File Format | |
| ISSN | 08937648 |
| Journal | Molecular Neurobiology |
| Volume Number | 53 |
| Issue Number | 2 |
| e-ISSN | 15591182 |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2015-01-07 |
| Publisher Place | New York |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Silibinin Oxidative stress Antioxidant Neuron Autophagy Apoptosis Survival Neurosciences Neurobiology Cell Biology Neurology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neurology Cellular and Molecular Neuroscience |
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