Protective effects of a herbal extract combination of Bupleurum falcatum, Paeonia suffruticosa, and Angelica dahurica against MPTP-induced neurotoxicity via regulation of nuclear receptor-related 1 protein. (6th January 2017)

• Record Type: Journal Article
• Authors: Sim, Yeomoon; Park, Gunhyuk; Eo, Hyeyoon; Huh, Eugene; Gu, Pil Sung; Hong, Seon-Pyo; Pak, Youngmi Kim; Oh, Myung Sook
• Is Part Of: Neuroscience. Volume 340(2017)
• Page Start: 166
• Page End: 175
• Publication Date: 2017-01-06
• Subjects: 6-OHDA 6-hydroxydopamine -- DAT dopamine transporter -- ERK extracellular signal-regulated kinase -- HPLC high-performance liquid chromatography -- MABH herbal extract combination of Bupleuri Radix, Moutan Cortex Radicis and Angelica Dahuricae Radix -- MPTP 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine -- Nurr1 nuclear receptor-related 1 protein -- PBS phosphate-buffered saline -- PD Parkinson's disease -- ROP ropinirole -- SNpc substantia nigra pars compacta -- ST striatum -- TH tyrosine hydroxylase -- T-LA time for locomotion activity -- T-turn time to turn -- VMAT2 vesicular monoamine transporter 2 -- VTA ventral tegmental area; Bupleurum falcatum -- Paeonia suffruticosa -- Angelica dahurica -- Parkinson's disease -- 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine -- nuclear receptor-related 1 protein; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2016.10.029
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: MABH improved MPTP-induced movement impairments in mice. MABH prevented dopamine depletion and protected against MPTP-induced dopaminergic neuron damage in mice. MABH increased Nurr1 expression in the SNpc of mice. MABH increased TH, DAT, and VMAT2 expressions by upregulating Nurr1 via phosphorylation of ERK in PC12 cells. Abstract: Parkinson's disease (PD) is one of the progressive neurodegenerative diseases of whose condition is characterized by dopaminergic neuronal cell loss and dysfunction in the substantia nigra pars compacta (SNpc) and the striatum. Recent studies have demonstrated that the nuclear receptor-related 1 protein (Nurr1) is critical of dopaminergic phenotype induction in mesencephalic dopaminergic neurons. Further, Nurr1 engages in synthesizing and storing dopamine through regulating levels of tyrosine hydroxylase (TH), dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2). The aim of this study was to investigate the protective effects of a herbal extract combination, consisting of Bupleurum falcatum, Paeonia suffruticosa, and Angelica dahurica (MABH), on 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD-like symptoms and to elucidate possible mechanisms of action focusing on Nurr1. In a subacute mouse model of MPTP-induced PD, MABH treatment resulted in recovery from movement impairments. MABH prevented dopamine depletion and protected against dopaminergic neuronal degradation induced by MPTP. Additionally, MABH increased Nurr1 expression in the SNpc of mice. To evaluate the effects of MABH on Nurr1 expression, we measured the protein levels of Nurr1 and its regulating factors using Western blot analysis in PC12 cells. MABH treatment induced the phosphorylation of extracellular signal-regulated kinase protein via increasing the protein expression levels of Nurr1 and ultimately the levels of TH, VMAT2, and DAT. These results indicate that MABH has protective effects on dopaminergic neurons in a mouse model of PD by regulating Nurr1.