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Aging (Albany NY). 2019 Oct 7;11. doi: 10.18632/aging.102337. [Epub ahead of print]

Probucol, a "non-statin" cholesterol-lowering drug, ameliorates D-galactose induced cognitive deficits by alleviating oxidative stress via Keap1/Nrf2 signaling pathway in mice.

Author information

1
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Pharmacy School, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
2
Scientific research center of traditional Chinese medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi 530200, China.

Abstract

Oxidative stress plays a vital role in the initiation and progression of age-related neurodegenerative diseases. Ameliorating oxidative damage is therefore considered as a beneficial strategy for the treatment of age-related neurodegenerative disorders. Probucol (Prob), a lipid-lowering prototype agent, was reported to treat cardiovascular diseases, chronic kidney disease and diabetes mellitus. However, whether Prob has an effect on age-related neurodegenerative diseases remains unknown. In the study, it was found that Prob ameliorated D-galactose (D-gal) induced cognitive deficits and neuronal loss in the hippocampal CA1 region. Moreover, Prob alleviated ROS and MDA levels by elevating SOD, GSH-PX and HO-1 mRNA and protein expressions, and improving plasmic and cerebral SOD and GSH-PX activities in D-gal treated mice. Furthermore, Prob promoted the dissociation of Keap1/Nrf2 complex leading to the accumulation of Nrf2 in nucleus, implying that the improved anti-oxidant property of Prob is mediated by Keap1/Nrf2 pathway. The study firstly demonstrates the favorable effects of Prob against cognitive impairments in a senescent mouse model, rendering this compound a promising agent for the treatment or prevention of age-related neurodegenerative disease.

KEYWORDS:

Keap1/Nrf2 pathway; age-related neurodegenerative disease; oxidative stress; probucol

PMID:
31590160
DOI:
10.18632/aging.102337
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