Luteolin-7-O-glucoside protects dopaminergic neurons by activating estrogen-receptor-mediated signaling pathway in MPTP-treated mice

Abstract Background Parkinson's disease (PD) is a neurodegenerative disorder that is characterized by the degeneration of dopaminergic neurons in substantia nigra (SN). Accumulating evidences implicated the beneficial role of estrogen in the therapy of PD. Methods In the present study, the protective function of luteolin-7-O-glucoside (LUT-7 G), 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) treated mice. Results The pre-treatment of LUT-7 G 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-7 G enhanced the gene transcription of estrogen receptor (ER), ERα and ERβ and ERK1/2/STAT3/c-Fos that could be abolished by ER antagonists. Furthermore, in vivo experiment indicated that the pre-treatment of LUT-7 G improved the bradykinesia, and enhanced the muscle strength as well as the balancing capacity of mice treated with MPTP. Further study showed that LUT-7 G repaired the injured TH positive cells in substantia nigra and increased TH positive nerve fibers in striatum. In addition, the pre-treatment of LUT-7 G also significantly diminished the MPTP-induced gliosis in substantia nigra. Conclusions LUT-7 G 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-7 G for PD therapy.