Journal
TOXICOLOGY
Volume 426, Issue -, Pages -Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2019.152256
Keywords
Parkinson's disease; Luteolin-7-O-glucoside; Estrogen receptor; Dopaminergic neuron; 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)
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Funding
- Shanghai Sailing Program [17YF1417700]
- Natural Science Foundation of Shanghai [17ZR1430500]
- Shanghai University of Traditional Chinese Medicine [2016YSN27]
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BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder that is characterized by the degeneration of dopaminergic neurons in substantia nigra (SN). Accumulating evidences implicate the beneficial role of estrogen in the therapy of PD. METHODS: In the present study, the protective function of luteolin-7-O-glucoside (LUT-7G), a natural flavonoid, was investigated in 1-methyl-4-phenylpyridinium (MPP+) treated SH-SY5Y cells and 1- methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) induced mice. RESULTS: Pre-treatment of LUT-7G increased the viability and reduced the apoptosis of SH-SY5Y cells treated by MPP+. At molecular level, the Bcl-2/Bax ratio was increased, while the expression of cleaved caspase 3 was markedly lessened. Moreover, LUT-7G increased the expression of estrogen receptor (ER), ER alpha and ER beta, and enhanced the activation of ERK1/2/STAT3/c-Fos that could be abolished by ER antagonists. Furthermore, in vivo experiment indicated that pre-treatment of LUT-7G improved the bradykinesia, and enhanced the muscle strength as well as the balancing capacity of mice treated with MPTP. And LUT-7G prevented the injury of TH positive cells in substantia nigra and increased TH positive nerve fibers in striatum. In addition, pre-treatment of LUT-7G also significantly diminished the MPTP-induced gliosis in substantia nigra. CONCLUSIONS: LUT-7G effectively protected dopaminergic neurons against MPP+ or MPTP-induced toxicity, probably by activating the ER-mediated signaling pathway. Our findings explore the therapeutic potential of LUT-7G for PD therapy.
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