Article

Neuroprotective effects of emodin in rat cortical neurons against beta-amyloid-induced neurotoxicity.

Department of Human Anatomy and Histology & Embryology, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
Brain research (Impact Factor: 2.83). 08/2010; 1347:149-60. DOI: 10.1016/j.brainres.2010.05.079
Source: PubMed

ABSTRACT Accumulation of beta-amyloid protein (Abeta) in the brain plays an important role in the pathogenesis of Alzheimer's disease (AD). In this study, the neuroprotective effect of emodin extracted from the traditional Chinese medicinal herb Polygonum cuspidatum Sieb. et Zucc against Abeta(25-35)-induced cell death in cultured cortical neurons was investigated. We found that pre-treatment with emodin prevented the cultured cortical neurons from beta-amyloid-induced toxicity. The preventive effect of emodin was blocked by pre-treatment with a phosphatidylinositol-3-kinase (PI3K) pathway inhibitor LY294002 or an estrogen receptor (ER) specific antagonist ICI182780, but not by pre-treatment with an extracellular signal-related kinases (ERK) inhibitor U0126. Furthermore, we found that emodin exposure induced the activation of the Akt serine/threonine kinase and increased the level of Bcl-2 expression. Moreover, the application of emodin for 24h was able to induce the activation of Abeta(25-35)-suppressed Akt and decrease the activation of the Jun-N-terminal kinases (JNK), but not of ERK. Interestingly, the up-regulation of Akt and Bcl-2 did not occur in the presence of LY294002 or ICI182780, suggesting that emodin-up-regulated Bcl-2 is mediated via the ER and PI3K/Akt pathway. Taken together, our results suggest that emodin is an effective neuroprotective drug and is a viable candidate for treating AD.

0 Followers
 · 
124 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: One of the pathological hallmarks of Alzheimer's disease (AD) is the progressive accumulation of beta-amyloid (Aβ) in the form of senile plaques, and Aβ induced neurotoxicity has been identified as a major cause of the onset of AD. In this study, we investigated the protective effects of a polysaccharide (PS-WNP) from Polygonatum sibiricum against the Aβ25-35-induced neurotoxicity in PC12 cells and explored the underlying mechanism. The results showed that pretreatment with PS-WNP significantly attenuated cell death and the elevated Bax/Bcl-2 ratio evoked by Aβ25-35, and subsequently inhibited mitochondrial dysfunction and cytochrome c release into the cytosol. Moreover, PS-WNP significantly inhibited Aβ25-35 induced caspase-3 activation and enhanced the protein levels of phosphorylated Akt (p-Akt) in PC12 cells. Additionally, pretreatment with the PI3K inhibitor (LY294002) completely abolished the protective effects of PS-WNP against Aβ25-35-induced neuronal cell apoptosis. These observations unambiguously suggested that the protective effect of PS-WNP against Aβ25-35-induced apoptosis in PC12 cells was associated with the enhancement of PI3K/Akt signaling pathway. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Carbohydrate Polymers 03/2015; 117:879-86. DOI:10.1016/j.carbpol.2014.10.034 · 3.92 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Autophagy plays an important role in the pathogenesis of Alzheimer's disease. In the present study, the blockade mechanism of emodin on amyloid-β 25-35-induced neurotoxicity was explored. Cell viability of PC12 cells was evaluated by the MTT assay and neuro damage by the lactate dehydrogenase leakage assay. Gene silencing by small interfering RNA, cDNA constructs and transfection, as well as Western blot were performed to assess protein expression levels. AβPP/PS1 mice were administered orally with emodin (50 mg/kg/day), and LC3-II positive cells in their brain cortex sections were detected by immunohistochemical staining. Emodin could significantly inhibit the LC3-I/LC3-II conversion ratio and cell viability while decreasing the lactate dehydrogenase level in AβPP/PS1 mice and PC12 cells. LC3II positive cells in the cortex were decreased significantly by the treatment with both emodin and 3-methyladenine. Furthermore, emodin and 3-methyladenine could increase B-cell lymphoma 2 while decreasing Beclin-1 and hVps34 expressions, which were induced by amyloid-β 25-35. Small interfering gene silencing Beclin-1 and B-cell lymphoma 2 confirmed this signaling pathway. We also found that the phosphatidylinositol 3-kinase inhibitor LY294002 could block LC3-I/LC3-II conversion and increase B-cell lymphoma 2 while decreasing hVps34 and Beclin-1 expressions. The results suggest that the blockade of emodin on amyloid-β 25-35-induced autophagy may occur via the activation of the class III phosphatidylinositol 3-kinase/Beclin-1/B-cell lymphoma 2 pathway. Our results provide confirmatory evidence for the application of emodin in the prevention and treatment of Alzheimer's disease. Georg Thieme Verlag KG Stuttgart · New York.
    Planta Medica 01/2015; 81(02). DOI:10.1055/s-0034-1383410 · 2.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Alzheimer's disease (AD) is a common neurodegenerative disorder, in which progressive neuron loss, mainly in the hippocampus, is observed. The critical events in the pathogenesis of AD are associated with accumulation of β-amyloid (Aβ) peptides in the brain. Deposits of Aβ initiate a neurotoxic “cascade” leading to apoptotic death of neurons. Aim of this study was to assess a putative neuroprotective effects of two nootropic drugs: piracetam (PIR) and levetiracetam (LEV) on Aβ-injured hippocampal neurons in culture. Methods Primary cultures of rat's hippocampal neurons at 7 day in vitro were exposed to Aβ(25–35) in the presence or absence of nootropics in varied concentrations. Flow cytometry with Annexin V/PI staining was used for counting and establishing neurons as viable, necrotic or apoptotic. Additionally, release of lactate dehydrogenase (LDH) to the culture medium, as a marker of cell death, was evaluated. Results Aβ(25–35) caused concentration-dependent death of about one third number of hippocampal neurons, mainly through an apoptotic pathway. In drugs-containing cultures, number of neurons injured with 20 μM Aβ(25–35) was about one-third lesser for PIR and almost two-fold lesser for LEV. When 40 μM Aβ(25–35) was used, only LEV exerted beneficial neuroprotective action, while PIR was ineffective. Conclusions Our results suggest the protective potential of both studied nootropics against Aβ-induced death of cultured hippocampal neurons with more powerful neuroprotective effects of LEV.
    Pharmacological reports: PR 01/2014; 67(2). DOI:10.1016/j.pharep.2014.09.013 · 2.17 Impact Factor