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Rosmarinic acid protects against MPTP-induced toxicity and inhibits iron-induced α-synuclein aggregation.

Neuropharmacology (2018-10-22)
Le Qu, Huamin Xu, Wenting Jia, Hong Jiang, Junxia Xie
ABSTRACT

Rosmarinic acid (RA) is a naturally occurring polyphenolic compound. In this study, we demonstrated that RA could protect against the degeneration of the nigrostriatal dopaminergic system in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of Parkinson's disease (PD). In addition, RA could inhibit MPTP-induced decrease of superoxide dismutase (SOD) and tyrosine hydroxylase (TH) and increase in nigral iron content. Further studies elucidated the effects of RA on iron-induced neurotoxicity and the possible underlying mechanisms in the SK-N-SH cells. Results showed that iron could induce a decrease in the mitochondrial transmembrane potential and result in α-synuclein aggregation in the SK-N-SH cells, which could be restored by RA pretreatment. Further results showed RA pretreatment could inhibit iron-induced α-synuclein aggregation by up-regulating hemeoxygenase-1 (HO-1). In addition, iron could increase the mRNA levels of α-synuclein via iron responsive element/iron regulatory protein (IRE/IRP) system. RA pretreatment could decrease the mRNA levels of α-synuclein by decreasing the protein levels of IRP1. These results indicated that RA protected against iron-induced α-synuclein aggregation by up-regulating HO-1 and inhibiting α-synuclein expression.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Dopamine hydrochloride
Sigma-Aldrich
Ammonium iron(III) citrate, reagent grade, powder
Sigma-Aldrich
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride, powder
Sigma-Aldrich
Rhodamine 123, mitochondrial specific fluorescent dye
Sigma-Aldrich
Rosmarinic acid, ≥98% (HPLC), from Rosemarinus officinalis L.
Sigma-Aldrich
Thioflavine S, practical grade
Sigma-Aldrich
Iron(II) sulfate heptahydrate, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥99%
Sigma-Aldrich
Rosmarinic acid, 96%
Sigma-Aldrich
3,4-Dihydroxyphenylacetic acid, 98%
Sigma-Aldrich
Homovanillic acid, Fluorimetric reagent