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Probucol, a "Non-Statin" Cholesterol-Lowering Drug, Ameliorates D-galactose Induced Cognitive Deficits by Alleviating Oxidative Stress via Keap1/Nrf2 Signaling Pathway in Mice

Probucol, a "Non-Statin" Cholesterol-Lowering Drug, Ameliorates D-galactose Induced Cognitive Deficits by Alleviating Oxidative Stress via Keap1/Nrf2 Signaling Pathway in Mice

Jin-Lan Huang, Chao Yu, Min Su, Si-Man Yang, Fan Zhang, Yuan-Yuan Chen, Jin-Yuan Liu, Yi-Fan Jiang, Zhen-Guo Zhong, Deng-Pan Wu

Aging (Albany NY). 2019 Oct 7;11(19):8542-8555.

PMID: 31590160

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP2455143	Probucol Related Compound A		2455-14-3	Price

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