J Korean Neurol Assoc.  2007 Aug;25(3):353-363.

Inhibition of Oxidative Tissue Damage and Mitochondrial Dysfunction by Glycyrrhizin in the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Mouse Model of Parkinson's Disease

• Park SE
• Hong KM
• Han JH
• Kim DE
• Lee CS

Abstract

BACKGROUND: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces an irreversible and severe parkinsonian-like syndrome. A licorice compound glycyrrhizin exerts a cytoprotective or anti-oxidant effect in various disease conditions, but its effect against the MPTP-induced brain tissue damage remains uncertain. The present study elucidates the protective effects of glycyrrhizin against brain tissue damage in the MPTP mouse model of Parkinson's disease.
METHODS
We measured the activities of antioxidant enzymes and formation of tissue peroxidation products in the brains of MPTP-treated mice. We also performed an in vitro assay to examine the effects of 1-methyl-4-phenylpyridinium (MPP+) on the mitochondrial respiratory electron flow, membrane potential and cytochrome c release and measured the scavenging action of glycyrrhizin against reactive oxygen species.
RESULTS
The MPTP treatment increased activities of total superoxide dismutase, catalase, and glutathione peroxidase and levels of malondialdehyde and carbonyls in the basal ganglia, diencephalon plus midbrain compared to the control mouse brain. Co-administration of glycyrrhizin (16.8 mg/kg = 20 micrometer) attenuated the MPTP effect on the enzyme activities and formation of tissue peroxidation products. Glycyrrhizin attenuated the 500 micrometer MPP+ -induced inhibition of electron flow, changes in the membrane potential and cytochrome c release in isolated brain mitochondria. Glycyrrhizin (1-50 micrometer) showed a scavenging action against superoxide radicals, hydrogen peroxide and hydroxyl radicals.
CONCLUSIONS
Glycyrrhizin may prevent the toxicity of MPTP against brain tissue by suppressing mitochondrial damage and oxidative tissue damage. Glycyrrhizin seems to attenuate oxidative brain tissue damage occurring in Parkinson's disease through antioxidant action and prevention of mitochondrial dysfunction.

Keyword

Glycyrrhizin; MPTP; MPP+; Brain tissue; Mitochondrial function; Protection

MeSH Terms

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine*
1-Methyl-4-phenylpyridinium
Animals
Antioxidants
Basal Ganglia
Brain
Catalase
Cytochromes c
Diencephalon
Glutathione Peroxidase
Glycyrrhiza
Glycyrrhizic Acid*
Hydrogen Peroxide
Malondialdehyde
Membrane Potentials
Mesencephalon
Mice*
Mitochondria
Parkinson Disease*
Reactive Oxygen Species
Superoxide Dismutase
Superoxides
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
1-Methyl-4-phenylpyridinium
Antioxidants
Catalase
Cytochromes c
Glutathione Peroxidase
Glycyrrhizic Acid
Hydrogen Peroxide
Malondialdehyde
Reactive Oxygen Species
Superoxide Dismutase
Superoxides