Neuroprotective effects of emodin in rat cortical neurons against β-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: 2.84). 08/2010; 1347(C):149-60. DOI: 10.1016/j.brainres.2010.05.079
Source: PubMed


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.

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    • "Previous studies also demonstrated that overexpression of antioxidant enzymes and pretreatment with an antioxidant compound attenuated Aβinduced apoptotic cell death (Aruoma et al. 2003; Anderton 1994). The PI3K signaling pathway plays a central role in neuronal survival (Koh et al. 2003; Franke et al. 2003), with studies showing that activation of PI3K prevents Aβ-induced neuronal death (Liu et al. 2010; Zhao et al. 2011; Zeng et al. 2011; Lou et al. 2011). Previous data also demonstrated that luteolin blocks the PI3K-AKT-NF-κB-ERK 1/2 pathway and attenuates the increase in ROS and elevates the Bcl-2/Bax ratio, leading to decreased apoptotic cell death (Zhou et al. 2011). "
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    Applied Microbiology and Biotechnology 10/2015; DOI:10.1007/s00253-015-7001-7 · 3.34 Impact Factor
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    • "So far, studies concerning the relationship between Bcl-2 and the mPTP opening have been rarely reported. Furthermore, many investigations show that the expression of Bax is increased and the expression of Bcl-2 is decreased in Aβ1-42-induced neuronal apoptosis [15]–[17]. These results imply that Aβ1-42 induces the mPTP opening which might be regulated by Bcl-2 family proteins. "
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    ABSTRACT: Mitochondrial dysfunction caused by amyloid β-peptide (Aβ) plays an important role in the pathogenesis of Alzheimer disease (AD). Substantial evidence has indicated that the mitochondrial permeability transition pore (mPTP) opening is involved in Aβ-induced neuronal death and reactive oxygen species (ROS) generation. Astragaloside IV (AS-IV), one of the major active constituents of Astragalus membranaceus, has been reported as an effective anti-oxidant for treating neurodegenerative diseases. However, the molecular mechanisms still need to be clarified. In this study, we investigated whether AS-IV could prevent Aβ1-42-induced neurotoxicity in SK-N-SH cells via inhibiting the mPTP opening. The results showed that pretreatment of AS-IV significantly increased the viability of neuronal cells, reduced apoptosis, decreased the generation of intracellular reactive oxygen species (ROS) and decreased mitochondrial superoxide in the presence of Aβ1-42. In addition, pretreatment of AS-IV inhibited the mPTP opening, rescued mitochondrial membrane potential (ΔΨm), enhanced ATP generation, improved the activity of cytochrome c oxidase and blocked cytochrome c release from mitochondria in Aβ1-42 rich milieu. Moreover, pretreatment of AS-IV reduced the expression of Bax and cleaved caspase-3 and increased the expression of Bcl-2 in an Aβ1-42 rich environment. These data indicate that AS-IV prevents Aβ1-42-induced SK-N-SH cell apoptosis via inhibiting the mPTP opening and ROS generation. These results provide novel insights of AS-IV for the prevention and treatment of neurodegenerative disorders such as AD.
    PLoS ONE 06/2014; 9(6):e98866. DOI:10.1371/journal.pone.0098866 · 3.23 Impact Factor
    • "Aloe–emodin has been reported to induce the apoptosis of human nasopharyngeal carcinoma cells (Lin et al., 2010b). Emodin exerts antidiabetic and antitumour activities (Xue et al., 2010; Wang et al., 2010; Hsu et al., 2010) and has been investigated for its lipid-lowering and neuroprotective effects in rat cortical neurons (Du et al., 2009; Liu et al., 2010). Although appreciable experimental evidence and ethnobotanical data have accumulated concerning the anticancer properties of Polygonaceae species (Hartwell, 1970), no comprehensive screening studies have yet been published on the plants of this family. "
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    ABSTRACT: Aqueous and organic extracts of 27 selected species from five genera (Fallopia, Oxyria, Persicaria, Polygonum and Rumex) of the family Polygonaceae occurring in the Carpathian Basin were screened in vitro for antiproliferative activity against HeLa (cervix epithelial adenocarcinoma), A431 (skin epidermoid carcinoma) and MCF7 (breast epithelial adenocarcinoma) cells, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. A total of 196 n-hexane, chloroform, 50% methanol or water extracts of different plant parts were investigated. It was found that extracts of Polygonum hydropiper, Rumex acetosa, Rumex alpinus, Rumex aquaticus, Rumex scutatus and Rumex thyrsiflorus at 10 or 30 µg/mL demonstrated substantial cell growth inhibitory activity (at least 50% inhibition of cell proliferation) against one or more cell lines. R. acetosa and R. thyrsiflorus proved to be the most active and are considered worthy of activity-guided phytochemical investigations. Copyright © 2012 John Wiley & Sons, Ltd.
    Phytotherapy Research 01/2013; 27(1). DOI:10.1002/ptr.4690 · 2.66 Impact Factor
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