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Luteolin, a natural flavonoid, inhibits methylglyoxal induced apoptosis via the mTOR/4E-BP1 signaling pathway.

Luteolin, a natural flavonoid, inhibits methylglyoxal induced apoptosis via the mTOR/4E-BP1 signaling pathway.
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Liu Y, Huang J, Zheng X, Yang X, Ding Y, Fang T, Zhang Y, Wang S, Zhang X, Luo X, Guo A, Newell KA, Yu Y, Huang XF,


Liu Y, Huang J, Zheng X, Yang X, Ding Y, Fang T, Zhang Y, Wang S, Zhang X, Luo X, Guo A, Newell KA, Yu Y, Huang XF, (click to view)

Liu Y, Huang J, Zheng X, Yang X, Ding Y, Fang T, Zhang Y, Wang S, Zhang X, Luo X, Guo A, Newell KA, Yu Y, Huang XF,

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Scientific reports 2017 08 117(1) 7877 doi 10.1038/s41598-017-08204-6
Abstract

Methylglyoxal (MG) accumulation has been observed in human cerebrospinal fluid and body tissues under hyperglycaemic conditions. Recent research has demonstrated that MG-induces neuronal cell apoptosis, which promotes the development of diabetic encephalopathy. Our previous animal study has shown that luteolin, a natural flavonoid, attenuates diabetes-associated cognitive dysfunction. To further explore the neuroprotective properties of luteolin, we investigated the inhibitive effect of luteolin on MG-induced apoptosis in PC12 neuronal cells. We found that MG inhibited cell viability in a dose-dependent manner and induced apoptosis in PC12 cells. Pretreatment with Luteolin significantly elevated cell viability, reduced MG-induced apoptosis, inhibited the activation of the mTOR/4E-BP1 signaling pathway, and decreased pro-apoptotic proteins, Bax, Cytochrome C as well as caspase-3. Furthermore, we found that pretreatment with the mTOR inhibitor, rapamycin, significantly reduced the expression of the pro-apoptotic protein Bax. Therefore, these observations unambiguously suggest that the inhibitive effect of Luteolin against MG-induced apoptosis in PC12 cells is associated with inhibition of the mTOR/4E-BP1 signaling pathway.

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