Asiatic acid protects differentiated PC12 cells from Aβ(25-35)-induced apoptosis and tau hyperphosphorylation via regulating PI3K/Akt/GSK-3β signaling.

Amyloid β (Aβ) peptide can cause neurotoxicity in Alzheimer's disease (AD). The main purpose of the present study is to investigate the protective role of asiatic acid (AA) against Aβ25-35-induced neurotoxicity in neuronally differentiated PC12 cells. Differentiated PC12 cells were pretreated with 5, 10 or 20 μM AA before treatment with 20 μM Aβ25-35. The viability and apoptosis of differentiated PC12 cells were determined by MTT assay and Annexin V-FITC/PI double staining, respectively. The mitochondrial membrane potential (MMP) of differentiated PC12 cells was analyzed by JC-1 staining. The expression levels of proteins were detected by western blot analysis. We found that AA significantly increased the viability of differentiated PC12 cells but attenuated the mitochondria-mediated apoptosis dose-dependently when challenging with Aβ25-35. Besides, the results of western blot analysis showed that AA prevented IκBα degradation and p65 nuclear translocation, and promoted the phosphorylation of Akt and GSK-3β in Aβ25-35-treated differentiated PC12 cells. Moreover, LY294002, a specific PI3K inhibitor, was found to abolish the beneficial effects of AA on Aβ25-35-induced apoptosis and tau protein hyperphosphorylation. Our findings demonstrated that AA protects differentiated PC12 cells from Aβ25-35-induced apoptosis and tau protein hyperphosphorylation, which might be partially mediated by the activation of the PI3K/Akt/GSK-3β signaling pathway.

Cheng W ，Chen W ，Wang P ，Chu J ... -  《-》

Ginsenoside Rg2 protects PC12 cells against β-amyloid(25-35)-induced apoptosis via the phosphoinositide 3-kinase/Akt pathway.

Alzheimer's disease (AD) is one of the most debilitating neurodegenerative diseases in an aging population. Excessive accumulation of β-amyloid (Aβ) has been proposed as a pivotal event in the pathogenesis of AD. Ginsenoside Rg2 has been reported to exert neuroprotective effects. However, the underlying mechanism for its neuroprotection is not well-understood. In this study, we investigated the protective effects of ginsenoside Rg2 on Aβ25-35-induced neurotoxicity in PC12 cells and identified a potential molecular signaling pathway involved. The results showed that pretreatment of PC12 cells with ginsenoside Rg2 followed by Aβ25-35 increased cell viability in a concentration-dependent manner compared to cells that were not pretreated. In addition, ginsenoside Rg2 pretreatment attenuated Aβ25-35-induced increases in the release of lactate dehydrogenase, the intracellular calcium concentration, and levels of reactive oxygen species. Pretreatment with ginsenoside Rg2 increased the Bcl-2/Bax ratio. Moreover, ginsenoside Rg2 attenuated the cleavage of caspase-3 induced by Aβ25-35 thereby improving cell survival. Ginsenoside Rg2 significantly enhanced the phosphorylation of Akt in PC12 cells. Additionally, pretreatment with the phosphoinositide 3-kinase (PI3K) inhibitor, LY294002, completely abolished the protective effects of ginsenoside Rg2 against Aβ25-35-induced neuronal cell apoptosis. These findings unambiguously suggested that the protective effect of ginsenoside Rg2 against Aβ25-35-induced apoptosis in PC12 cells was associated with enhancement of the PI3K/Akt signaling pathway.

Cui J ，Wang J ，Zheng M ，Gou D ，Liu C ，Zhou Y ... -  《-》

Propofol may protect PC12 cells from β-amyloid₂₅₋₃₅ induced apoptosis through the GSK-3β signaling pathway.

Zhang R ，Xu J ，Liu YY ，Zuo PP ，Yang N ，Ji C ，Wang Y ，Wang H ，Wu AS ，Yue Y ... -  《-》

Neuroprotective effects of linarin through activation of the PI3K/Akt pathway in amyloid-β-induced neuronal cell death.

Linarin, a natural occurring flavanol glycoside derived from Mentha arvensis and Buddleja davidii is known to have anti-acetylcholinesterase effects. The present study intended to explore the neuroprotective effects of linarin against Aβ(25-35)-induced neurotoxicity with cultured rat pheochromocytoma cells (PC12 cells) and the possible mechanisms involved. For this purpose, PC12 cells were cultured and exposed to 30 μM Aβ(25-35) in the absence or presence of linarin (0.1, 1.0 and 10 μM). In addition, the potential contribution of the PI3K/Akt neuroprotective pathway in linarin-mediated protection against Aβ(25-35)-induced neurotoxicity was also investigated. The results showed that linarin dose-dependently increased cell viability and reduced the number of apoptotic cells as measured by MTT assay, Annexin-V/PI staining, JC-1 staining and caspase-3 activity assay. Linarin could also inhibit acetylcholinesterase activity induced by Aβ(25-35) in PC12 cells. Further study revealed that linarin induced the phosphorylation of Akt dose-dependently. Treatment of PC12 cells with the PI3K inhibitor LY294002 attenuated the protective effects of linarin. Furthermore, linarin also stimulated phosphorylation of glycogen synthase kinase-3β (GSK-3β), a downstream target of PI3K/Akt. Moreover, the expression of the anti-apoptotic protein Bcl-2 was also increased by linarin treatment. These results suggest that linarin prevents Aβ(25-35)-induced neurotoxicity through the activation of PI3K/Akt, which subsequently inhibits GSK-3β and up-regulates Bcl-2. These findings raise the possibility that linarin may be a potent therapeutic compound against Alzheimer's disease acting through both acetylcholinesterase inhibition and neuroprotection.

Lou H ，Fan P ，Perez RG ，Lou H ... -  《-》

Isorhynchophylline treatment improves the amyloid-β-induced cognitive impairment in rats via inhibition of neuronal apoptosis and tau protein hyperphosphorylation.

Xian YF ，Mao QQ ，Wu JC ，Su ZR ，Chen JN ，Lai XP ，Ip SP ，Lin ZX ... -  《-》