Lutein attenuated methylglyoxal-induced oxidative damage and apoptosis in PC12 cells via the PI3K/Akt signaling pathway.

Methylglyoxal (MGO), a cytotoxic byproduct of glycolysis, causes neuro oxidative damage and apoptosis, and plays key roles in diabetic encephalopathy (DE). The goal of this research was to evaluate the roles of lutein attenuated MGO-induced damage in PC12 cells as well as the underlying mechanisms. The findings of this study showed that lutein has a significant impact on reducing the generation of reactive oxygen species (ROS) and oxidative stress in MGO-induced PC12 cells, which may be attributed to the increased antioxidant enzymes activity and the decreased MDA levels. Moreover, treatment with lutein also alleviated cell apoptosis and mitochondrial damage. Real-time PCR and western blot analysis showed that lutein enhanced the Bcl-2:Bax ratio, inhibited the expression of caspase-3 and caspase-9, and increased the protein level of phosphorylated Akt. The network pharmacology and molecular docking prediction results suggested that the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway was a potential mechanism of lutein in DE treatment. Furthermore, LY294002, a specific PI3K inhibitor, partially abolished the protective effect of lutein. These results presented that lutein attenuated oxidative damage and apoptosis triggered by MGO in PC12 cells via the PI3K/Akt signaling pathway. PRACTICAL APPLICATIONS: Lutein is a common carotenoid dispersed in fruits and vegetables. This article confirmed a protective effect of lutein on oxidative damage and apoptosis in PC12 cells after MGO damage. These results indicated that lutein could potentially be developed as a nutraceutical or functional food in the prevention of diabetic-related neurodegenerative diseases.

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