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

Accumulation of β-amyloid protein (Aβ) 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 againstAβ _25-35-induced cell death in cultured cortical neurons was in vestigated. We found that pre-treatment with emodin prevented the cultured cortical neurons from β-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 antagonistICI182780, 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 24 h was able to induce the activation of Aβ_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.