Gastrodin prevents motor deficits and oxidative stress in the MPTP mouse model of Parkinson's disease: involvement of ERK1/2-Nrf2 signaling pathway

Abstract

Aims: Current no effective therapy is available to halt the progression of Parkinson's disease (PD). Oxidative stress has been implicated in the etiology of PD. The present study evaluates the hypothesis that prevention of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor deficits by gastrodin might mainly result from its antioxidant property via interrupting extracellular signal regulated protein kinases (ERK) 1/2-nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway.

Main methods: Pretreatment of mouse model of PD is established by treating C57BL/6 mice with 4 doses of MPTP (30 mg/kg per day, i.p.), with gastrodin (60 mg/kg per day) administered by daily intraperitoneal injection for 2 weeks. Motor behavior of mice was monitored by open-field test and rotarod test. Real-time polymerase chain reaction and Western blotting were used to analyze the expression of genes.

Key findings: MPTP-induced motor deficits were partially and significantly forestalled by gastrodin. Gastrodin treatment prevented MPTP-induced oxidative stress, as measured by malondialdehyde in midbrain. Interestingly, MPTP-intoxicated mice treated with gastrodin robustly increased heme oxygenase 1, superoxide dismutase, glutathione levels, and Nrf2 nuclear translocation in striatum of MPTP-intoxicated mice. Furthermore, results herein suggest that the antioxidant pathway activated by gastrodin involves ERK1/2 phosphorylation.

Significance: Gastrodin protects midbrain of MPTP-intoxicated mice against oxidative stress, in part, through interrupting ERK1/2-Nrf2 pathway mechanism, which will give us an insight into the potential of gastrodin in terms of opening up new therapeutic avenues for PD.

Keywords: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (PubChem CID: 1388); Curcumol (PubChem CID: 115067); Gastrodin; Glutathione; Oxidative stress; Parkinson's disease; Rotarod test.