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PLoS One. 2012;7(4):e35823. doi: 10.1371/journal.pone.0035823. Epub 2012 Apr 23.

Diammonium glycyrrhizinate upregulates PGC-1α and protects against Aβ1-42-induced neurotoxicity.

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  • 1Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.

Abstract

Mitochondrial dysfunction is a hallmark of beta-amyloid (Aβ)-induced neurotoxicity in Alzheimer's disease (AD), and is considered an early event in AD pathology. Diammonium glycyrrhizinate (DG), the salt form of Glycyrrhizin, is known for its anti-inflammatory effects, resistance to biologic oxidation and membranous protection. In the present study, the neuroprotective effects of DG on Aβ(1-42)-induced toxicity and its potential mechanisms in primary cortical neurons were investigated. Exposure of neurons to 2 µM Aβ(1-42) resulted in significant viability loss and cell apoptosis. Accumulation of reactive oxygen species (ROS), decreased mitochondrial membrane potential, and activation of caspase-9 and caspase-3 were also observed after Aβ(1-42) exposure. All these effects induced by Aβ(1-42) were markedly reversed by DG treatment. In addition, DG could alleviate lipid peroxidation and partially restore the mitochondrial function in Aβ(1-42)-induced AD mice. DG also significantly increased the PGC-1α expression in vivo and in vitro, while knocking down PGC-1α partially blocked the protective effects, which indicated that PGC-1α contributed to the neuroprotective effects of DG. Furthermore, DG significantly decreased the escape latency and search distance and increased the target crossing times of Aβ(1-42)-induced AD mice in the Morris water maze test. Therefore, these results demonstrated that DG could attenuate Aβ(1-42)-induced neuronal injury by preventing mitochondrial dysfunction and oxidative stress and improved cognitive impairment in Aβ(1-42)-induced AD mice, indicating that DG exerted potential beneficial effects on AD.

PMID:
22540007
[PubMed - indexed for MEDLINE]
PMCID:
PMC3335163
Free PMC Article
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