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

J Korean Neurol Assoc > Volume 25(3); 2007 > Article

Journal of the Korean Neurological Association 2007;25(3): 353-363.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine 생쥐 파킨슨병 모델에서 Glycyrrhizin에 의한 산화적 조직 손상 및 사립체 기능 이상의 억제

박상은, 홍기무 한정호 김두응 이정수a

서울 보훈병원 신경과, 중앙대학교 의과대학 약리학교실a

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

Sang-Eun Park

Department of Neurology, Seoul Veterans Hospital, Seoul, Korea Department of Pharmacology, College of Medicine, Chung-Ang Universitya, Seoul, Korea

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 μM) attenuated the MPTP effect on the enzyme activities and formation of tissue peroxidation products. Glycyrrhizin attenuated the 500 μM MPP+- induced inhibition of electron flow, changes in the membrane potential and cytochrome c release in isolated brain mitochondria. Glycyrrhizin (1-50 μM) 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. KeyWords:Glycyrrhizin, MPTP, MPP+, Brain tissue, Mitochondrial function, Protection