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.
"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 –. These results imply that Aβ1-42 induces the mPTP opening which might be regulated by Bcl-2 family proteins. "
[Show abstract][Hide abstract] 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. "
[Show abstract][Hide abstract] ABSTRACT: San-Huang-Xie-Xin-Tang (SHXT), composed of Coptidis rhizoma, Scutellariae radix, and Rhei rhizoma, is a traditional Chinese medicine used for complementary and alternative therapy of cardiovascular and neurodegenerative diseases via its anti-inflammatory and antioxidative effects. The aim of this study is to investigate the protective effects of SHXT in the 1-methyl-4-phenylpyridinium (MPP(+))/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models of Parkinson's disease. Rat primary mesencephalic neurons and mouse Parkinson disease model were used in this study. Oxidative stress was induced by MPP(+) in vitro and MPTP in vivo. In MPP(+)-treated mesencephalic neuron cultures, SHXT significantly increased the numbers of TH-positive neurons. SHXT reduced apoptotic signals (cytochrome and caspase) and apoptotic death. MPP(+)-induced gp91(phox) activation and ROS production were attenuated by SHXT. In addition, SHXT increased the levels of GSH and SOD in MPP(+)-treated neurons. In MPTP animal model, SHXT markedly increased TH-positive neurons in the substantia nigra pars compacta (SNpc) and improved motor activity of mice. In conclusion, the present results reveal the evidence that SHXT possesses beneficial protection against MPTP-induced neurotoxicity in this model of Parkinson's disease via its antioxidative and antiapoptotic effects. SHXT might be a potentially alternative and complementary medicine for neuroprotection.
Evidence-based Complementary and Alternative Medicine 03/2012; 2012(13):501032. DOI:10.1155/2012/501032 · 1.88 Impact Factor
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