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-1β 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.
Highlights
As the population increases and lifespan is extended, the aging population becomes large and aging-related diseases have brought great attention worldwide
We found that D-gal treatment induced noticeably aging-related changes, including cognitive impairment and memory deficits; decrease in swimming time in the weight-loaded swimming test and thymus coefficient; increase in senescence-associated β-galactosidase (SA-βgal) activity; p16, p19, p21, interleukin- (IL-) 1β and IL-6 gene expression; and oxidative stress in the liver, spleen, and brain
D-gal caused a decrease in the difference between training and test for the object recognition index with the comparison of the control group, whereas pretreatment of vitamin E (VE) (100 mg/kg) and MAT (2 and 10 mg/kg, oral) abolished the partial amnesic effect of D-gal (Figure 2(b)) (p < 0 01, p < 0 01, and p < 0 001)
Summary
As the population increases and lifespan is extended, the aging population becomes large and aging-related diseases have brought great attention worldwide. Aging is one of the major factors of brain decline involved in gradual learning and memory loss, cognitive disorders, and dementia, like Alzheimer’s disease [1, 2]. High levels of ROS could induce oxidative stress and destroy the structure of DNA, phospholipids, and proteins, resulting in cellular and tissue injury [9]. This is a critical mechanism for ROS-induced aging. Mammalian cells have an antioxidant system able to scavenge high levels of ROS. Total superoxide dismutase (T-SOD), catalase (CAT), and vitamin E (VE) are the critical members of this antioxidant system [10]
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