Search

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. [ABSTRACT FROM AUTHOR]

D-pinitol (DP) has been extensively regarded as the main active component of legumes for anti-aging. In this study, we intended to explore the anti-aging mechanism of DP, utilizing computer modeling techniques. The results demonstrated that DP significantly delayed H 2 O 2 -induced cellular senescence. Model PC12 cells treated with DP exhibited increased cell viability, increased antioxidant enzyme activity (SOD, CAT), and reduced ROS and MDA levels. Furthermore, DP was discovered to have a positive effect on healthy longevity. In C. elegans , DP treatment enhanced lifespan, stress capacity, antioxidant capacity (T-SOD/CAT/GSH-Px/MDA/ROS), and altered aging-related indicators of lipofuscin accumulation, pharyngeal pump rate, motility, and reproduction. Moreover, DP could reduce the toxicity Aβ in transgenic C. elegans CL4176, CL2355, and CL2331. Further mechanistic studies indicated DP increased transcription factor (daf-16 , skn-1 , hsf-1) expression of insulin/insulin-like growth factor-1 signaling (IIS) pathway. As expected, DP also extended the downstream target genes of the three transcription factors (sod-3 , ctl-1 , ctl-2 , gst-4 , hsp-16.1 , and hsp-16.2). Further mutant lifespan experiments, network pharmacology, and molecular docking revealed that DP might be life-extending through the IIS pathway. DP deserves extensive investigation and development as a potential anti-aging drug in the future. [Display omitted] • Network pharmacology showed the anti-aging effect of DP was mediated by IIS pathway. • Both in vivo and in vitro experiments have shown that DP has an anti-aging effect. • DP exerted anti-aging effects through IIS signaling pathway. • The key genes of DP and IIS pathways were verified by molecular docking technology. [ABSTRACT FROM AUTHOR]