Abstract
Our previous works have shown that dioscin, a natural product, has various pharmacological activities, however, its role in brain aging has not been reported. In the present study, in vitro H2O2-treated PC12 cells and in vivo d-galactose-induced aging rat models were used to evaluate the neuroprotective effect of dioscin on brain aging. The results showed that dioscin increased cell viability and protected PC12 cells against oxidative stress through decreasing reactive oxygen species (ROS) and lactate dehydrogenase (LDH) levels. In vivo, dioscin markedly improved the spatial learning ability and memory of aging rats, reduced the protein carbonyl content and aging cell numbers, restored the levels of superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px), malondialdehyde (MDA) and nitric oxide synthase (NOS) in brain tissue, and reversed the histopathological structure changes of nerve cells. Mechanism studies showed that dioscin markedly adjusted the MAPK and Nrf2/ARE signalling pathways to decrease oxidative stress. Additionally, dioscin also significantly decreased inflammation by inhibiting the mRNA or protein levels of TNF-α, IL-1β, IL-6, CYP2E1 and HMGB1. Taken together, these results indicate that dioscin showed neuroprotective effect against brain aging via decreasing oxidative stress and inflammation, which should be developed as an efficient candidate in clinical to treat brain aging in the future.
Highlights
Aging of the population is a common problem around the world
The results indicated that dioscin improved the ultrastructure of neurons in aging rats to exert its neuroprotective effect
These results suggested that the protective effects of dioscin against brain aging are through ameliorating neuroinflammation
Summary
Aging of the population is a common problem around the world. According to data from a 2017United Nations report, the number of older people aged 60 or over will grow from 962 million to nearly2.1 billion by 2050 [1]. Brain aging can cause the decline of learning and memory ability, and accelerate the aging process and increase the possibility of suffering from age-related diseases (ARDs) [2,3], which are rapidly becoming a huge strain for medical care and public health systems [4]. The pathogenesis of brain aging is very complicated, oxidative stress and inflammation are closely associated with the disease. Neurons tend to accumulate oxidatively-damaged molecules [6,7,8], and excessive reactive oxygen species (ROS) can cause aging and death of nerve cells [9]. Chronic and low-grade inflammation has been observed in the aging brain [10,11]. Microglia can exhibit enhanced sensitivity to inflammatory stimuli, and the increased levels of inflammatory cytokines can lead to Molecules 2019, 24, 1247; doi:10.3390/molecules24071247 www.mdpi.com/journal/molecules
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