Dataset Information

Matrine Attenuates D-Galactose-Induced Aging-Related Behavior in Mice via Inhibition of Cellular Senescence and Oxidative Stress.

ABSTRACT: The present study was designed to evaluate the effects of matrine (MAT) on D-galactose- (D-gal-) induced aging and relative mechanism. Vitamin E at the dose of 100?mg/kg was used as a standard positive control. MAT significantly improved the D-gal-induced recognition and spatial memory impairment in novel object recognition and Y maze tests, and exercise endurance decreased in the weight-loaded swimming test at 2 and 10?mg/kg. We found that D-gal treatment induced noticeably aging-related changes such as reducing thymus coefficients, increasing the pathological injury and cellular senescence of liver, spleen, and hippocampus, as well as an increase in cyclin-dependent kinase inhibitor p16, p19, and p21 gene expression and the interleukin-1? expression in the liver and hippocampus. MAT showed effective protection on such changes. Furthermore, MAT decreased the oxidative stress of the liver, plasma, and brain, as evidenced by increased total antioxidant capacity, total superoxide dismutase, and catalase activities and decreased the malondialdehyde level. Additionally, there was a significant positive correlation between swimming time in weight-loaded swimming time and thymus index. MAT ameliorated aging-related disorder caused by D-gal through the inhibition of both cellular senescence and oxidative stress. The study provides further evidence for drug development of MAT for prevention or treatment of the aging-associated disorder.

SUBMITTER: Sun K

PROVIDER: S-EPMC6288577 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Matrine Attenuates D-Galactose-Induced Aging-Related Behavior in Mice <i>via</i> Inhibition of Cellular Senescence and Oxidative Stress.

Sun Kaiyue K Yang Pengyu P Zhao Rong R Bai Yuting Y Guo Zijiao Z

Oxidative medicine and cellular longevity 20181127

The present study was designed to evaluate the effects of matrine (MAT) on D-galactose- (D-gal-) induced aging and relative mechanism. Vitamin E at the dose of 100 mg/kg was used as a standard positive control. MAT significantly improved the D-gal-induced recognition and spatial memory impairment in novel object recognition and Y maze tests, and exercise endurance decreased in the weight-loaded swimming test at 2 and 10 mg/kg. We found that D-gal treatment induced noticeably aging-related change ...[more]

PMID: 30598725

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Project description:Both environmental exposure to vanadium pentoxide (V2O5, V+5 for its ionic counterparts) and fibroblast senescence are associated with pulmonary fibrosis, but whether V+5 causes fibroblast senescence remains unknown. We found in a dose-response study that 2-40 μM V+5 caused human lung fibroblasts (HLF) senescence with increased senescence-associated β-galactosidase activity and p16 expression, while cell death occurred at higher concentration (LC50, 82 μM V+5). Notably, measures of reactive oxygen species (ROS) production with fluorescence probes showed no association of ROS with V+5-dependent senescence. Preloading catalase (polyethylene-conjugated), a H2O2 scavenger, did not alleviate the cellular senescence induced by V+5. Analyses of the cellular glutathione (GSH) system showed that V+5 oxidized GSH, increased GSH biosynthesis, stimulated cellular GSH efflux and increased protein S-glutathionylation, and addition of N-acetyl cysteine inhibited V+5-elevated p16 expression, suggesting that thiol oxidation mediates V+5-caused senescence. Moreover, strong correlations between GSSG/GSH redox potential (Eh), protein S-glutathionylation, and cellular senescence (R2 > 0.99, p < 0.05) were present in V+5-treated cells. Studies with cell-free and enzyme-free solutions showed that V+5 directly oxidized GSH with formation of V+4 and GSSG in the absence of O2. Analyses of V+5 and V+4 in HLF and culture media showed that V+5 was reduced to V+4 in cells and that a stable V+4/V+5 ratio was rapidly achieved in extracellular media, indicating ongoing release of V+4 and reoxidation to V+5. Together, the results show that V+5-dependent fibroblast senescence is associated with a cellular/extracellular redox cycling mechanism involving the GSH system and occurring under conditions that do not cause cell death. These results establish a mechanism by which environmental vanadium from food, dietary supplements or drinking water, can cause or contribute to lung fibrosis in the absence of high-level occupational exposures and cytotoxic cell death.

Dataset Information

Matrine Attenuates D-Galactose-Induced Aging-Related Behavior in Mice via Inhibition of Cellular Senescence and Oxidative Stress.

Publications

Matrine Attenuates D-Galactose-Induced Aging-Related Behavior in Mice <i>via</i> Inhibition of Cellular Senescence and Oxidative Stress.

Similar Datasets

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