Cyperi Rhizoma inhibits the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced reduction in nigrostriatal dopaminergenic neurons in estrogen-deprived mice

Abstract

Ethnopharmacological relevance: Cyperi Rhizoma has commonly been used for the treatment of gynecological and neuropsychiatric disorders in traditional medicine. The aim of this study was to evaluate the estrogenic properties and neuroprotective effects of Cyperi Rhizoma under estrogen-deprived condition in female mice.

Materials and methods: To determine the estrogen-like effect of Cyperi Rhizoma extract (CRE), we measured luciferase expression after transfection of a promoter construct containing an estrogen response element (ERE) and treatment of CRE. To evaluate the neuroprotective effect of CRE, we measured striatal dopamine, movement ability, tyrosine hydroxylase (TH) immunoreactivity, and apoptosis-related protein expression levels after treatment of CRE either with or without 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in ovariectomized female mice.

Results: CRE significantly induced the luciferase expression driven by an ERE in PC12 cells, a dopaminergic cell line, in a dose-dependent manner. In mice, MPTP significantly decreased the levels of dopamine in the striatum and behavior performance; in contrast, both CRE and 17β-estradiol benzoate (EB) recovered these parameters to normal levels. CRE and EB treatment also recovered TH immunopositive fibers and cells, respectively, from MPTP toxicity. Additionally, MPTP significantly down-regulated Bcl-2 expression in the mitochondria of dopaminergic cells in the SN, followed by an increase in Bax expression, cytochrome C translocation to the cytosol, and cleaved-caspase-3 expression, whereas these were inhibited by CRE or EB treatment.

Conclusions: These findings provide the first evidence that CRE has estrogen-like and neuroprotective effects on dopaminergic neurons in estrogen-deprived mice treated with MPTP-toxin.